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    The EU Clinical Trials Register currently displays   43881   clinical trials with a EudraCT protocol, of which   7295   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2022-002500-21
    Sponsor's Protocol Code Number:Apollo01
    National Competent Authority:Netherlands - Competent Authority
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2023-03-04
    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 ConcernedNetherlands - Competent Authority
    A.2EudraCT number2022-002500-21
    A.3Full title of the trial
    Neo-adjuvant Pembrolizumab in vulvar squamous cell carcinoma:
    a clinical proof-of-concept study.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Neo-adjuvant Pembrolizumab in vulvar squamous cell carcinoma:
    a clinical study.
    A.3.2Name or abbreviated title of the trial where available
    Neo-adjuvant Pembrolizumab in vulvar squamous cell carcinoma: a clinical proof-of-concept study.
    A.4.1Sponsor's protocol code numberApollo01
    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 SponsorLUMC
    B.1.3.4CountryNetherlands
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportOncode Institute
    B.4.2CountryNetherlands
    B.4.1Name of organisation providing supportMSD
    B.4.2CountryNetherlands
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationLeiden University Medical Center
    B.5.2Functional name of contact pointMariette van Poelgeest
    B.5.3 Address:
    B.5.3.1Street AddressAlbinusdreef 2
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333ZA
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+3171526 2845 / 4050
    B.5.6E-mailm.i.e.van_poelgeest@lumc.nl
    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 Yes
    D.2.1.1.1Trade name KEYTRUDA (pembrolizumab, MK3475)
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme B.V.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.3Other descriptive nameMK-3475
    D.3.9.4EV Substance CodeSUB167136
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Vulvar squamous cell carcinoma (VSCC)

    Clinically diagnosed FIGO I-III primary VSCC patients to be treated with surgery with curative intent
    E.1.1.1Medical condition in easily understood language
    schaamlipkanker
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    1. To study the clinical efficacy of neoadjuvant PD-1 blockade in VSCC, as measured by an objective change in tumor size (according to RECIST 1.1) and documented by calipers using standardized digital photography with reference ruler) at the time of surgery (approximately 6 weeks after first administration Pembrolizumab).
    2. To study the activation, proliferation and migration of CD4+CD39+PD-1+ effector T cell population upon PD-1 blockade.
    E.2.2Secondary objectives of the trial
    1. To study pathological complete responses (pCR) at time of surgery
    2. To study feasibility(defined as delay in planned surgery and surgical outcome), safety according to NCI-CTC version 5.0
    3. To study the activation, proliferation and migration of the CD8+CD103+CD39+PD-1+ intratumoral T-cell population upon PD-1 blockade.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed written informed consent prior to performance of study-specific procedures or
    assessments, and must be willing to comply with treatment and follow-up assessments.
    2. Age ≥ 18 years old at the day of signing informed consent
    3. Histologically confirmed primary vulvar squamous cell carcinoma, with all of the following characteristics:
    - At least 1 lesion that can be measured in at least 1 dimension with ≥ 10 mm in largest diameter.
    - Clinically stage FIGO I-III.
    - Documentation confirming the absence of distant metastasis (M0) as determined by institutional practice. Routine exams to discard metastases will be performed according to Investigator judgement but are mandatory in case of suspicion of metastatic disease.
    - Vulvar cancer eligible for primary surgery
    - In the case of a multifocal tumor (defined as the presence of two or more foci of cancer on the vulva), the largest lesion must be ≥ 10 mm and all lesions ≥ 10 mm are designated as "target" lesion(s) for all subsequent tumor evaluations and biopsies.
    4. ECOG performance 0-1
    5. Have adequate organ function as measured within 28 days prior to administration of study treatment, as defined: Hemoglobin > 10.0 g/dL or > 6.2 mmol/L, with no blood transfusions the past 28 days; Absolute neutrophil count (ANC) > 1500/µL; Platelets > 100 000/µL, with no platelet transfusion in the past 28 days; Total bilirubin ≤ 1.5 x ULN (not applicable to Gilbert’s syndrome with an upper limit of 2.5 ULN); AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; Creatinine clearance (using the Cockcroft-Gault equation or 24 hr urine clearance) ≥51 mL/min; UNL= institutional upper limit of normal (ULN); AST(SGOT)= Aspartate aminotransferase (Serum Glutamic Oxaloacetic Transaminase); ALT(SGPT)= Alanine aminotransferase (Serum Glutamic Pyruvate Transaminase (SGPT)

    6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
    • Is not a woman of childbearing potential, or
    • Is a woman of childbearing potential and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is 120 days for pembrolizumab.
    E.4Principal exclusion criteria
    1. Locally advanced tumor not amenable to surgical therapy.
    2. A woman of child bearing potential who has a positive urine pregnancy test within 72 hours prior to allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
    3. Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD37)
    4. Prior systemic anti-cancer therapy including investigational agents within 4 weeks [prior to allocation.
    Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
    Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
    5. Prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
    6. Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
    7. A live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette– Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. Please refer to section 5.4 for information on COVID-19 vaccines.
    8. Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
    9. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
    10. A known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin on a location other than the vulva, or carcinoma in situ (e.g. of the breast , cervix or bladder) that have undergone potentially curative therapy are not excluded.
    11. Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
    12. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
    - Patients with vitiligo or alopecia
    - Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
    - Any chronic skin condition that does not require systemic therapy
    - Patients without active disease in the last 5 years may be included but only after consultation with the study physician
    - Patients with celiac disease controlled by diet alone
    13. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis
    14. An active infection requiring systemic therapy.
    15. Known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
    16. Known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
    17. A history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the subject’s participation for the full duration of the study in such it is not in the best interest of the subject to participate, in the opinion of the treating investigator.
    18. Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
    19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
    20. Has had an allogenic tissue/solid organ transplant.
    E.5 End points
    E.5.1Primary end point(s)
    1. The percentage of patients with an objective clinical response defined as objective change in tumour size (according to RECISTv1.1)
    2. The activation, proliferation and migration of CD4+CD39+PD-1+ effector T cell population upon PD-1 blockade.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At baseline and at surgery (10 weeks)
    E.5.2Secondary end point(s)
    1. Pathological complete responses (pCR) at time of surgery
    2. The feasibility (defined as delay in planned surgery and surgical outcomes), safety of neoadjuvant PD-1 blockade in VSCC according to NCI-CTC version 5.0 criteria.
    3. The activation, proliferation and migration of the CD39+CD103+CD8+PD-1+ T cell population.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. At baseline and at surgery (10 weeks)
    2. At baseline and at surgery (10 weeks), week 13 and week 16
    3. At baseline and at surgery (10 weeks)
    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 No
    E.6.7Pharmacodynamic Yes
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Clinical responders can move into extension cohort
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned3
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    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: 40
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 40
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state40
    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)
    Responders have the option to fall into an extension cohort and, after consultation with the multidisciplinary team, will be treated with adjuvant pembrolizumab from week 16 until week 58 (400 mg IV, Q6W, 7 times). These patients will be monitored for long term effects, including blood collections for safety values and digital photography of the vulva.
    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 Decision2023-04-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2023-02-27
    P. End of Trial
    P.End of Trial StatusOngoing
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