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    Summary
    EudraCT Number:2021-001205-73
    Sponsor's Protocol Code Number:IMP4297-202
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-07-19
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2021-001205-73
    A.3Full title of the trial
    A Randomized, Double-Blinded, Placebo-Controlled, Multicenter, Phase II Study to Evaluate Senaparib Maintenance in mCRPC Patients with Homologous Recombination Repair Gene Alterations after Docetaxel Treatment
    Estudio de fase II, aleatorizado, en doble ciego, controlado con placebo y multicéntrico, para evaluar el tratamiento de mantenimiento con senaparib en pacientes con cáncer de próstata metastásico resistente a la castración y alteraciones génicas de la vía de reparación por recombinación homóloga tras el tratamiento con docetaxel
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    The metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations who have not progressed after docetaxel therapy
    Pacientes con cáncer de próstata metastásico resistente a la castración y alteraciones génicas de la vía de reparación por recombinación homóloga tras el tratamiento con docetaxel
    A.4.1Sponsor's protocol code numberIMP4297-202
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorIMPACT Therapeutics, Inc.
    B.1.3.4CountryChina
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportIMPACT Therapeutics, Inc.
    B.4.2CountryChina
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationIMPACT Therapeutics, Inc.
    B.5.2Functional name of contact pointYunru Chen
    B.5.3 Address:
    B.5.3.1Street AddressRoom 603, Building 3, xiangke Road 111
    B.5.3.2Town/ cityShanghai
    B.5.3.3Post code201210
    B.5.3.4CountryChina
    B.5.6E-mailclinical.research@impacttherapeutics.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameSenaparib
    D.3.2Product code IMP4297
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSenaparib
    D.3.9.1CAS number 1401682-78-7
    D.3.9.2Current sponsor codeIMP4297
    D.3.9.4EV Substance CodeSUB218614
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    metastatic castration-resistant prostate cancer (mCRPC)
    cáncer de próstata metastásico resistente a la castración (mCRPC)
    E.1.1.1Medical condition in easily understood language
    metastatic prostate cancer
    cáncer de próstata metastásico
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10036909
    E.1.2Term Prostate cancer metastatic
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10076506
    E.1.2Term Castration-resistant prostate cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the impact of Senaparib maintenance on radiographic progression free survival (rPFS), compared with the placebo, in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination repair (HRR) gene alterations who have not progressed after docetaxel therapy assessed by Blinded Independent Central Review (BICR)
    Evaluar el impacto del tratamiento de mantenimiento con senaparib sobre la supervivencia sin progresión radiográfica (radiographic progression free survival, rPFS), en comparación con el placebo, en pacientes con cáncer de próstata metastásico resistente a la castración (metastatic castration-resistant prostate cancer, mCRPC) y alteraciones génicas de la vía de reparación por recombinación homóloga (homologous recombination repair, HRR) que no han progresado después del tratamiento con docetaxel, según la evaluación del Servicio de revisión central con enmascaramiento independiente (Blinded Independent Central Review, BICR).
    E.2.2Secondary objectives of the trial
    To evaluate the impact of Senaparib maintenance on rPFS, assessed by investigator, rPFS in BRCA1, BRCA2 or ATM mutation positive patients assessed by BICR, time to prostate-specific antigen (PSA) progression, time to pain progression, time to the first symptomatic skeletal related events (SSRE), radiographic response rate, PSA response rate, second progression (PFS2), overall survival (OS), safety, compared with the placebo.
    To characterize the pharmacokinetics (PK) of Senaparib based on a population PK (PopPK) modeling approach.
    Evaluar el impacto del tratamiento de mantenimiento con senaparib sobre la rPFS, según la evaluación efectuada por el investigador, sobre rPFS con positividad para mutaciones del BRCA1, BRCA2 o ATM según la evaluación efectuada por el BICR, sobre el tiempo hasta la progresión del antígeno prostático específico (PSA), el tiempo hasta la progresión del dolor, el tiempo hasta los primeros acontecimientos sintomáticos esqueléticos (SSRE), sobre la tasa de respuestas radiográficas, sobre la tasa de respuesta del PSA, sobre la segunda progresión (PFS2), sobre la supervivencia global (overall survival, OS), seguridad, en comparació con placebo
    Describir la farmacocinética (pharmacokinetics, PK) de senaparib basándose en la elaboración de modelos de farmacocinética poblacional (population PK, PopPK).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients are eligible to be included in the study only if all the following criteria are met (* is for screening part 1, all criteria for screening part 2)
    1. Patients must voluntarily participate in this clinical study. Be willing and able to provide
    written informed consent form (ICF) prior to any study activity.
    2. Male ≥18 years of age on the day of signing the ICF.
    3. Patients must have histologically or cytologically confirmed prostate adenocarcinoma.
    4. Patients must have received and failed at least one novel hormonal agent (NHA, such as abiraterone, enzalutamide, etc.) before or in mCRPC stage. In addition, patients are allowed
    to have received and failed up to one novel hormonal therapy in mCRPC stage. Treatment
    failure is judged by the investigator.
    5. Patients confirmed by investigator to be at mCRPC stage when starting the immediate prior treatment with docetaxel. Metastatic disease documented by positive bone scan or metastatic lesions on CT or MRI. Metastatic lesions do not include disease spread to local pelvic lymph nodes or local disease recurrence (e.g., bladder and rectum).
    6. Surgically or medically castrated, with serum testosterone levels of ≤50 ng/dL (≤1.73 nmol/L). If the patient is being treated with LHRH agonists/antagonists (patient who have not undergone orchiectomy), this therapy must be continued throughout the study.
    7. Completed at least 6 cycles and a maximum of 8 cycles of immediate prior treatment with docetaxel (3 weeks a cycle) with no evidence of PD after last docetaxel treatment.
    The investigator must check whether the patient has PD according to the following four criteria, taking the baseline of docetaxel treatment as reference (if there is no radiographic tumor evaluation at baseline, the earliest tumor assessment after the first dose of docetaxel will serve as reference). Patients cannot be enrolled if they meet any of the four criteria for PD.
    a. Radiographic soft-tissue lesions progression according to RECIST v1.1.
    b. Radiographic bone progression according to Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria. Bone progression= appearance of 2 or more new lesions (only positivity on the bone scan defines metastatic disease to bone). Ambiguous results will be confirmed by other imaging modalities (e.g., CT or MRI).
    c. PSA progression according to PCWG3 criteria. PSA progression is defined as: PSA progression ≥25% increase and ≥2 ng/mL increase from baseline of docetaxel treatment beyond 12 weeks, and which is confirmed by a second value ≥3 weeks later.
    d. Clinical PD judged by investigator, including but not limited to skeletal-related events (SREs, e.g., asymptomatic or symptomatic fractures, surgery or radiation therapy to bone, or spinal cord compression), tumor related pain progression and other tumor related symptoms or signs.
    8. Documented germline/somatic mutation in at least one of the homologous recombination repair genes, including BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function) assessed by central laboratory using validated Next-Generation Sequencing (NGS) test from blood samples.
    9. Patients have adequate organ functions, as indicated by the following laboratory values (had not received blood transfusion, apheresis infusion, erythropoietin, granulocyte colony- stimulating factor (G-CSF), and other relevant medical support within 14 days before the administration of study drug):
    a. Haemoglobin ≥9.0 g/dL.
    b. Absolute neutrophil count (ANC) ≥1.5×109/L.
    c. Platelet count ≥100×109/L.
    d. Total bilirubin (TBIL) ≤1.5×institutional upper limit of normal (ULN) (not applicable for patients with Gilbert’s syndrome, whose enrollment should be discussed with the sponsor).
    e. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤3×institutional ULN unless liver metastases are present in which cases, they must be ≤5×ULN.
    f. Creatinine clearance ≥45 mL/min estimated using the Cockcroft-Gault equation.
    g. International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (APTT) ≤1.5×ULN. It is not applicable for patients with Gilbert’s syndrome, whose enrollment should be discussed with the sponsor. The INR only applies to patients who do not receive therapeutic anti-coagulation.
    10. Planned start of first dose of study drug 2 to 8 weeks after the last dose of docetaxel.
    11. Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
    12. Patients have a life expectancy of at least 16 weeks.

    For further details please refer to the protocol.
    Los pacientes serán elegibles para su inclusión en el estudio tan solo si cumplen todos los criterios siguientes (los marcados con * son aplicables a la parte 1 de la selección; para la parte 2 de la selección son aplicables todos los criterios):
    1.*Los pacientes deben participar voluntariamente en este ensayo clínico y estar de acuerdo en y ser capaces de otorgar su consentimiento por escrito mediante el documento de consentimiento informado (informed consent form, ICF) antes de realizarles cualquier actividad del estudio.
    2.*Varones >/=18 años el día de la firma del ICF.
    3.*Los pacientes deben presentar adenocarcinoma de próstata confirmado histológica o citológicamente.
    4.Los pacientes deberán haber recibido y haber presentado fracaso del tratamiento con como mínimo un nuevo agente hormonal (novel hormonal agent, NHA) (como abiraterona, enzalutamida, etc.), antes o durante la fase de cáncer de próstata metastásico resistente a la castración (metastatic castration-resistant prostate cancer, mCRPC). Adicionalmente, se permitirá que los pacientes hayan recibido y hayan presentado fracaso del tratamiento con un nuevo agente hormonal en la fase de mCRPC. La consideración de fracaso del tratamiento será a criterio del investigador.
    5.Pacientes que el investigador confirme que se encuentran en fase de mCRPC al iniciar el tratamiento con docetaxel inmediatamente previo. Enfermedad metastásica documentada mediante una gammagrafía ósea previa o lesiones metastásicas observadas en la tomografía computarizada (computed tomography, CT) o la resonancia magnética (magnetic resonance imaging, MRI). Las lesiones metastásicas no incluyen la invasión de los ganglios pélvicos locales ni la recidiva local de la enfermedad (p. ej., en la vejiga urinaria o el recto).
    6.Pacientes con castración quirúrgica o farmacológica, con niveles de testosterona sérica </=50 ng/dl (</=1,73 nmol/l). Si el paciente está siendo tratado con agonistas/antagonistas de la hormona liberadora de la hormona luteinizante (luteinizing hormone-releasing hormone, LHRH) (paciente que no se ha sometido a una orquiectomía), dicho tratamiento deberá continuar durante todo el estudio.
    7.El paciente deberá haber completado un mínimo de 6 ciclos y un máximo de 8 ciclos del tratamiento con docetaxel inmediatamente anterior (ciclos de 3 semanas) sin mostrar evidencias de progresión de la enfermedad (progressive disease, PD) después del último tratamiento con docetaxel.
    El investigador deberá comprobar si el paciente presenta PD según los cuatro criterios siguientes, tomando como referencia la situación basal al iniciar el tratamiento con docetaxel (si no se dispone de una evaluación radiológica tumoral basal, se utilizará como referencia la primera evaluación del tumor después de la primera administración de docetaxel). Los pacientes no podrán ser incluidos si presentan alguno de los cuatro criterios siguientes de PD:
    a.Progresión radiográfica de lesiones en partes blandas, según los criterios RECIST v1.1.
    b.Progresión ósea radiográfica según los criterios del Prostate Cancer Clinical Trials Working Group 3 (PCWG3). Progresión ósea = aparición de dos o más lesiones nuevas (la enfermedad metastásica ósea se define únicamente mediante una gammagrafía ósea positiva). Los resultados ambiguos se deben confirmar con otras modalidades de pruebas de imagen (p. ej., CT o MRI).
    c.Progresión del PSA según los criterios del PCWG3. La progresión del PSA se define como: Progresión del PSA: incremento >/=25% y >/=2 ng/ml respecto al valor basal del tratamiento con docetaxel durante más de 12 semanas, confirmado con un segundo valor al cabo de >/=3 semanas.
    d.PD clínica, según el criterio del investigador, que incluya, entre otros, acontecimientos esqueléticos (skeletal-related events, SREs) (p. ej., fracturas asintomáticas o sintomáticas, cirugía o radioterapia óseas o bien compresión de la médula espinal), progresión del dolor oncológico y otros síntomas o signos relacionados con el tumor.
    8.Mutación documentada de la línea germinal/somática en como mínimo uno de los genes de la vía de reparación por recombinación homóloga, que incluye BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D y RAD54L, que se prevea o sospeche que resultará perjudicial (que se sepa o se prevea que será nociva/que provocará pérdida de la función) según los análisis del laboratorio central mediante técnicas de secuenciación de nueva generación (Next-Generation Sequencing, NGS).
    9.Pacientes con función orgánica adecuada, indicada mediante los siguientes valores de laboratorio (y que no hayan recibido transfusiones de sangre, infusiones tras aféresis, eritropoyetina, factor estimulante de las colonias de granulocitos [granulocyte colony-stimulating factor, G-CSF] u otras medidas de soporte médico relevantes en el plazo de los 14 días previos a la administración del fármaco del estudio):

    Para mas criterios ver protocolo.
    E.4Principal exclusion criteria
    Patients who meet any of the following criteria will be excluded from the study (* is for screening part 1)
    1. *Previous allogenic bone marrow transplant or double umbilical cord blood transplantation
    (dUCBT).
    2. *Prior treatment with a polyadenosine 5'diphosphoribose polymerisation (PARP) inhibitor,
    including Senaparib.
    3. *In mCRPC stage, any prior systemic therapy except for docetaxel, NHA or necessary ADT
    with LHRH agonists/antagonist for mCRPC.
    4. *Patients with a known hypersensitivity to Senaparib or any of the component of Senaparib.
    5. Patients who have other new malignancies within 2 years prior to the first dose of Senaparib will be excluded, except for radically treated basal or squamous cell skin cancer. Patients with other malignancies which have been treated with no relapse within 2 years can be
    enrolled.
    6. Initiating bisphosphonate/denosumab therapy or adjusting bisphosphonate/denosumab
    dose/regimen within 28 days prior to the first dose of study drug. Patients on a stable bisphosphonate/denosumab regimen are eligible and may continue.
    7. Patients who have received chemotherapy (except for docetaxel), targeted therapy, immunotherapy, endocrine therapy (except for necessary ADT with LHRH
    agonists/antagonist for mCRPC), anti-tumor Chinese herbal medicine or proprietary
    Chinese medicine treatment or other anti-cancer systemic treatment within 5 half-lives or 28 days (whichever is longer), prior to the first dose of study drug.
    8. Patients who have any acute toxicities due to prior chemotherapy and/or radiotherapy that are >2 Grade per National Cancer Institute-Common Terminology Criteria for Adverse
    Events (NCI-CTCAE) v5.0 with the exception of alopecia.
    9. Patients who have participated in a study of an investigational agent and received study therapy or used an investigational device within 28 days of the first dose of study drug. For investigational drugs, the washout period should be 5 half-lives or 28 days whichever is
    longer.
    10. Patients who have received strong inhibitors/inducers of CYP3A4 which cannot be discontinued 21 days prior to the first dose of study drug and withheld throughout the study drug treatment. Patients received phenobarbital/enzalutamide will require a 5-week
    washout prior to the first dose of study drug.
    11. Patients who have undergone a major surgery or radical radiotherapy within 28 days prior to the first dose of study drug, or have undergone a palliative radiotherapy within 14 days
    prior to the first dose of study drug.
    12. *Patients with MDS or AML, or with clinical features suggestive of MDS or AML.
    13. Patients with serious acute or chronic infections.
    14. Patients who have acute myocardial infarction, unstable angina, stroke, or transient
    ischemic attack within 6 months prior to the first dose of study drug; patients who have congestive heart failure (New York Heart Association [NYHA] Classification Class ≥II); patients who have severe or uncontrolled hypertension, arrhythmia.
    15. Patients with known and symptomatic brain metastasis. Patients with asymptomatic, treated,
    stable brain metastases without steroids for at least 28 days are eligible for study entry. A radiographic imaging to confirm the absence of brain metastases is not required.
    16. Patients with symptomatic or impending spinal cord compression, unless appropriately
    treated for this and clinically stable and asymptomatic for 28 days prior to the first dose of study drug.
    17. Patients who are unable to swallow a whole capsule. Patients have gastrointestinal illnesses
    that may clinically and significantly affect the absorption of oral medication of study drug,
    e.g., ulcerative colitis, Crohn’s disease, chronic diarrhea with malabsorption, intractable nausea and vomiting, or have had a surgical procedure which could affect gastrointestinal absorption at discretion of investigators.
    18. Patients who have received a live virus or bacterial or RNA vaccination within 28 days prior
    to the first dose of study drug.
    19. Patients known to have a history of alcoholism or drug abuse within 2 years.
    20. Patients considered a high risk due to a serious, uncontrolled medical disorder, non-
    malignant systemic disease at discretion of investigators. Examples included but not limited to, uncontrolled grand mal seizures, hepatic sclerosis, superior vena cava syndrome, extensive interstitial bilateral lung disease or any psychiatric disorder that prohibit obtaining ICF.
    21. *Patients are unable or unwilling to abide by the study protocol or cooperate fully with the
    investigator or designee.
    Los pacientes quedarán excluidos del estudio si cumplen cualquiera de los siguientes criterios (los marcados con * se refieren a la parte 1 de la selección):
    1.*Trasplante alogénico de médula ósea o doble trasplante de sangre de cordón umbilical (double umbilical cord blood transplantation, dTSCU) previos.
    2.*Tratamiento previo con un inhibidor de la polimerización de la poliadenosina 5’difosforribosa (polyadenosine 5'diphosphoribose polymerisation, PARP), incluido Senaparib.
    3.*En la fase de mCRPC: cualquier tratamiento sistémico previo, a excepción del docetaxel, NHA o terapia de privación androgénica [androgen deprivation therapy, ADT] con agonistas/antagonista de la LHRH que sea necesaria para el mCRPC.
    4.*Pacientes con hipersensibilidad conocida a Senaparib o a cualquier componente de Senaparib.
    5.Se excluirá a los pacientes que hayan presentado otras neoplasias malignas nuevas en el plazo de los 2 años previos a la primera administración de Senaparib, a excepción del carcinoma escamoso y el carcinoma de células basales de la piel tratados con terapia radical. Los pacientes con otras neoplasias malignas que hayan sido tratados y no hayan presentado recidivas en los 2 años anteriores podrán ser incluidos en el estudio.
    6.Inicio de tratamiento con bisfosfonato/denosumab o ajuste de la dosis o la pauta de bisfosfonato/denosumab en los 28 días previos a la primera administración del fármaco en estudio. Los pacientes con una pauta estable de bisfosfonato/denosumab serán elegibles y podrán continuar con su tratamiento.
    7.Pacientes que hayan recibido quimioterapia (excepto docetaxel), terapias dirigidas, inmunoterapia, terapia hormonal (a excepción de la ADT con agonistas/antagonista de la LHRH que sea necesaria para el mCRPC), productos antitumorales de la medicina china derivados de hierbas o tratamientos aprobados de la medicina china u otro tratamiento antineoplásico sistémico en el plazo de 5 semividas del producto en cuestión o 28 días (lo que sea más prolongado) antes de la primera administración del fármaco en estudio .
    8.Pacientes con toxicidades agudas debidas a quimioterapia y/o radioterapia previas de Grado >2 según los Criterios terminológicos comunes para los acontecimientos adversos del Instituto Nacional del Cáncer de los Estados Unidos (National Cancer Institute-Common Terminology Criteria for Adverse Events, NCI-CTCAE) v5.0, a excepción de la alopecia.
    9.Pacientes que hayan participado en un estudio con un agente en investigación y hayan recibido el tratamiento del estudio o hayan utilizado un producto sanitario en investigación en el plazo de los 28 días previos a la primera dosis del fármaco en estudio. Para los fármacos en investigación, se aplicará un período de lavado de 5 semividas del fármaco o de 28 días, lo que sea más prolongado.
    10.Pacientes que hayan recibido inhibidores/inductores potentes del CYP3A4 si dichos fármacos no pueden suspenderse 21 días antes de la primera dosis del fármaco en estudio y mantenerse suspendidos durante todo el tiempo de tratamiento con el fármaco en estudio. Los pacientes que hayan sido tratados con fenobarbital/enzalutamida requerirán un período de lavado de 5 semanas antes de la primera administración del fármaco en estudio.
    11.Pacientes sometidos a cirugía mayor o a radioterapia radical en el plazo de los 28 días previos a la primera administración del fármaco en estudio o que hayan recibido radioterapia en el plazo de los 14 días anteriores a la primera administración del fármaco en estudio.
    12.*Pacientes con síndrome mielodisplásico (myelodysplastic syndrome, MDS) o leucemia mieloide aguda (acute myeloid leukemia, AML) o con características clínicas indicativas de MDS o AML.
    13.Pacientes con infecciones agudas o crónicas importantes.
    14.Pacientes que hayan presentado un infarto agudo de miocardio, angina inestable, ictus o accidente vascular cerebral isquémico transitorio en el plazo de los 6 meses previos a la primera administración del fármaco en estudio; pacientes con insuficiencia cardíaca congestiva (de Clase >/=II según la clasificación de la New York Heart Association [NYHA]); pacientes con hipertensión arterial o arritmia severas o no controladas.
    15.Pacientes con metástasis cerebrales sintomáticas conocidas. Podrán incluirse en el estudio aquellos pacientes que presenten metástasis cerebrales estables, asintomáticas y tratadas, que no hayan recibido corticoides durante los 28 días anteriores como mínimo. No es necesario practicar una prueba de diagnóstico por imagen para confirmar la ausencia de metástasis cerebrales
    Para mas criterios ver protocolo
    E.5 End points
    E.5.1Primary end point(s)
    rPFS assessed by BICR
    rPFS is defined as the time from randomization to the date of first radiographic disease progression (PD) or death from any cause, whichever occurs first. Radiographic PD will be evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria.
    rPFS evaluada por el BICR
    La rPFS se define como el tiempo transcurrido desde la aleatorización hasta la fecha de la primera progresión radiográfica de la enfermedad (progressive disease, PD) o la muerte por cualquier causa, lo que ocurra en primer lugar. La PD radiográfica se evaluará según los Criterios de Evaluación de la Respuesta de los Tumores Sólidos (Response Evaluation Criteria in Solid Tumors, RECIST) v1.1 y los criterios del Grupo de trabajo de ensayos clínicos del cáncer de próstata 3 (Prostate Cancer Clinical Trials Working Group 3, PCWG3).
    E.5.1.1Timepoint(s) of evaluation of this end point
    At the time when around 115 rPFS events are collected.
    DB lock planed May2021, Analysis Plan 1-2 month after DB lock. just a prediction.
    En el momento en el que se obtengan aproximadamente 115 eventos de rPFS
    El cierre de la base de datos esta planeada para mayo 2021, el plan de analisis para 1 o 2 meses despues del cierre de la base de datos. Es una prediccion
    E.5.2Secondary end point(s)
    1) rPFS assessed by the investigator;
    2) rPFS in BRCA1, BRCA2 or ATM mutation positive patients assessed by BICR;
    3) Time to PSA progression
    4) Time to pain progression
    5) Time from randomization to the first SSRE
    6) Objective response rate (ORR) according to RECIST v1.1 assessed by BICR
    7) ORR according to RECIST v1.1 assessed by the investigator
    8) PSA response rate
    9) Second progression (PFS2)
    10) Overall survival (OS)
    11) Safety: Adverse events (AEs), vital signs, physical examination, 12-lead electrocardiogram (ECG), and laboratory tests (including hematology, serum chemistry, urinalysis, and coagulation parameters)
    12) PK characteristics of Senaparib based on PopPK modeling approach, with the available data
    1)rPFS evaluada por el investigador
    2)rPFS en pacientes con positividad para mutaciones de BRCA1, BRCA2 o ATM, evaluada por el BICR
    3)Tiempo hasta la progresión del PSA
    4)Tiempo hasta la progresión del dolor
    5)Tiempo desde la aleatorización hasta el primer SSRE
    6)Tasa de respuestas objetivas (objective response rate, ORR) de acuerdo con los criterios RECIST v1.1, evaluada por el BICR.
    7)ORR según los criterios RECIST v1.1, evaluada por el investigador.
    8)Tasa de respuesta del PSA
    9)PFS2
    10)OS
    11)Seguridad: Acontecimientos adversos (adverse events, AEs), constantes vitales, exploración física, electrocardiograma (ECG) de 12 derivaciones y pruebas de laboratorio (hemograma, bioquímica sérica, análisis de orina y pruebas de coagulación).
    12)Características farmacocinéticas de senaparib mediante modelos de PopPK, con los datos disponibles.
    E.5.2.1Timepoint(s) of evaluation of this end point
    At the time when around 115 rPFS events are collected.
    DB lock planed May2021, Analysis Plan 1-2 month after DB lock. just a prediction.
    En el momento en el que se obtengan aproximadamente 115 eventos de rPFS
    El cierre de la base de datos esta planeada para mayo 2021, el plan de analisis para 1 o 2 meses despues del cierre de la base de datos. Es una prediccion
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA36
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Belgium
    France
    Germany
    Italy
    Netherlands
    Spain
    Switzerland
    Taiwan
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as the date when the last patient finished 2-year survival follow- ups, withdraws consent, being lost to follow-up, dies, or the study is terminated (whichever occurs first).
    El fin del estudio se define como la fecha en la que el ultimo paciente termina los dos años de seguimiento de supervivencia, haya retirada del consentimiento, pérdida durante el seguimiento, muerte o suspensión del estudio (lo que ocurra en primer lugar).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 65
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 100
    F.2 Gender
    F.2.1Female No
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 69
    F.4.2.2In the whole clinical trial 165
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Ninguno
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2021-07-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-06-02
    P. End of Trial
    P.End of Trial StatusOngoing
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