E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally Advanced or Metastatic Disease in Solid Tumors |
Tumeurs solides localement avancées ou métastatiques |
|
E.1.1.1 | Medical condition in easily understood language |
Locally Advanced or Metastatic Disease in Solid Tumors |
Tumeurs solides localement avancées ou métastatiques |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029521 |
E.1.2 | Term | Non-small cell lung cancer stage IIIB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029522 |
E.1.2 | Term | Non-small cell lung cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059515 |
E.1.2 | Term | Non-small cell lung cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033599 |
E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033600 |
E.1.2 | Term | Pancreatic adenocarcinoma non-resectable |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10051971 |
E.1.2 | Term | Pancreatic adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059326 |
E.1.2 | Term | Pancreatic carcinoma stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033610 |
E.1.2 | Term | Pancreatic carcinoma metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033609 |
E.1.2 | Term | Pancreatic carcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059333 |
E.1.2 | Term | Pancreatic carcinoma stage IVA |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059335 |
E.1.2 | Term | Pancreatic carcinoma stage IVB |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033604 |
E.1.2 | Term | Pancreatic cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061902 |
E.1.2 | Term | Pancreatic neoplasm |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071536 |
E.1.2 | Term | Head and neck cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071537 |
E.1.2 | Term | Head and neck cancer stage III |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10071540 |
E.1.2 | Term | Head and neck cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10010035 |
E.1.2 | Term | Colorectal cancer stage IV |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052358 |
E.1.2 | Term | Colorectal cancer metastatic |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052362 |
E.1.2 | Term | Metastatic colorectal cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10010023 |
E.1.2 | Term | Colorectal neoplasms malignant |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052360 |
E.1.2 | Term | Colorectal adenocarcinoma |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061873 |
E.1.2 | Term | Non-small cell lung cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
This study will evaluate the antitumor activity, safety, and pharmacokinetics (PK) of tisotumab vedotin in patients with locally advanced or metastatic tumors. |
Cette étude évaluera l'activité antitumorale, l'innocuité et la pharmacocinétique (PK) du tisotumab vedotin chez les patients présentant des tumeurs localement avancées ou métastatiques.
|
|
E.2.2 | Secondary objectives of the trial |
- Evaluate the safety and tolerability of tisotumab vedotin
- Evaluate preliminary antitumor activity of tisotumab vedotin
- Evaluate stability and control of disease
- Evaluate durability of response in patients who respond to tisotumab vedotin
- Evaluate the timing of responses
- Evaluate progression-free survival (PFS) of patients treated with tisotumab vedotin
- Evaluate survival of patients treated with tisotumab vedotin
- Assess pharmacokinetics of tisotumab vedotin
- Assess immunogenicity of tisotumab vedotin |
·Évaluer la sécurité d'emploi et la tolérance du tisotumab vedotin
·Évaluer l'activité antitumorale préliminaire du tisotumab vedotin
·Évaluer la stabilité et le contrôle de la maladie
·Évaluer la durabilité de la réponse mesurée par la durée de la réponse (DR)
·Évaluer le moment de la réponse
·Évaluer la survie sans progression (SSP) des patients traités avec le tisotumab vedotin
·Évaluer la survie des patients traités avec le tisotumab vedotin
·Évaluer la pharmacocinétique du tisotumab vedotin
.Évaluer l'immunogénicité du tisotumab vedotin |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Relapsed, locally-advanced or metastatic colorectal or pancreatic cancer, squamous NSCLC, or SCCHN that has failed prior lines of systemic treatment as specified and which are not candidates for standard therapy.
● Colorectal Cancer: Patients with colorectal cancer must have experienced disease progression on or after their most recent systemic therapy for non-operable metastatic disease. Isolated increase in carcinoembryonic antigen (CEA) will not qualify for study entry. Patients must have received prior therapy with each of the following agents, if eligible: a fluoropyrimidine, oxaliplatin, irinotecan, and/or bevacizumab. Patients with known/previously-tested RAS wild-type tumors and/or known/previously-tested MSI-H tumors could have received cetuximab or panitumumab and CPI, if eligible. Patients should have received no more than 3 systemic regimens in the metastatic setting.
● NSCLC: Patients with NSCLC must have histologically or cytologically-documented squamous cell NSCLC and must have experienced disease progression on or after their most recent systemic therapy for locally advanced or metastatic disease. Patients must have received prior therapy with a platinum-based regimen, a tyrosine kinase inhibitor (TKI; ALK, ROS-1 gene rearrangement or EGFR mutation), and a CPI if eligible for such therapy. Patients should have received no more than 2 systemic regimens in the locally advanced or metastatic setting.
● Exocrine pancreatic adenocarcinoma: Patients with exocrine pancreatic adenocarcinoma must have biopsy proven, histologically confirmed diagnosis of exocrine pancreatic adenocarcinoma and must have experienced disease progression on or after their most recent systemic therapy for locally advanced or metastatic disease. Isolated increase in CA 19-9 or CEA will not qualify for study entry. Patients must have received prior therapy with a gemcitabine-based or 5FU-based regimen if eligible for such therapy. Patients should have received no more than 1 systemic regimen in the unresectable or metastatic setting.
● SCCHN: Patients with SCCHN must have experienced disease progression on or after their most recent systemic therapy for recurrent or metastatic disease. Patients must not have tumors involving or adjacent to major blood vessels or a history of radiation involving major blood vessels in the radiation field. Patients must have received prior therapy with a platinum-based regimen and/or a CPI if eligible for such therapy. Patients eligible to receive anti-EGFR therapy must have received anti-EGFR therapy prior to study entry. Patients should have received no more than 2 systemic regimens in the recurrent/metastatic setting.
2. Measureable disease according to RECIST v1.1 as assessed by the investigator.
● A minimum of one non-nodal lesion ≥10 mm in the longest diameter from a non-irradiated area. If target lesion(s) are located within previously irradiated area only, the patient can be enrolled only if there has been demonstrated progression in the “in field” lesion and upon approval of the sponsor’s medical monitor.
● Lymph node lesion ≥15 mm in the shortest diameter from a non-irradiated area.
3. Age 18 years or older.
4. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
5. The following baseline laboratory data:
● absolute neutrophil count (ANC) ≥1500/μL assessed at least 2 weeks after growth factor support, if applicable.
● platelet count ≥100 x 109/L assessed at least 2 weeks after transfusion with blood products.
● hemoglobin ≥5.6 mmol/L (9.0 g/dL) assessed at least 2 weeks after transfusion with blood products and/or growth factor support.
● serum bilirubin ≤1.5 x upper limit of normal (ULN) or direct bilirubin ≤2 x ULN in patients diagnosed with Gilbert’s syndrome.
● estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73m2 using the Modification of Diet in Renal Disease (MDRD) study equation as applicable.
● alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN. (If liver tumor/metastases are present, then <5 x ULN is allowed).
6. Acceptable coagulation status.
7. Life expectancy of at least 3 months.
Other inclusion Criteria can be found in the Protocol. |
1. Cancer colorectal ou cancer du pancréas ou CPNPC épidermoïde ou CETC localement avancé ou métastatique et récidivant n'ayant pas répondu à des lignes de traitement systémique antérieures tel que spécifié et qui ne sont pas candidats à un traitement standard.
2. Maladie mesurable selon les critères RECIST v1.1 évalués par l'investigateur.
·Au moins une lésion non nodale ≥ 10 mm du plus grand diamètre dans une zone non irradiée. Si la/les lésion(s) cible(s) n'est/ne sont localisée(s) que dans la zone précédemment irradiée, le patient ne peut être inclus que si une progression de la lésion « dans le champ » a été démontrée et après approbation du moniteur médical du promoteur.
·Lésion ganglionnaire ≥ 15 mm du plus petit diamètre dans une zone non irradiée.
3. Âgés d'au moins 18 ans.
4. Un score à l'indice de performance de l'ECOG (Eastern Cooperative Oncology Group) de 0 ou 1 (voir l'annexe D du protocole pour la conversion de l'indice de performance à l'aide des échelles de Karnofsky et Lansky, le cas échéant).
5. Les valeurs de laboratoire suivantes à l'inclusion :
·une numération absolue des neutrophiles (NAN) ≥ 1500/µl évaluée au moins 2 semaines après l'administration de facteur de croissance, le cas échéant.
·une numération plaquettaire ≥ 100 x 109/l évaluée au moins 2 semaines après une transfusion de produits sanguins.
·une hémoglobine ≥ 5,6 mmol/l (9,0 g/dl) évaluée au moins 2 semaines après une transfusion de produits sanguins et/ou l'administration de facteur de croissance.
·un taux sérique de bilirubine < 1,5 fois la limite supérieure de la normale (LSN) ou un taux de bilirubine directe < 2 x LSN chez les patients ayant reçu un diagnostic de syndrome de Gilbert.
·un taux de filtration glomérulaire estimé (TFGe) ≥ 60 ml/min/1,73m2 en utilisant l'équation de l'étude MDRD (modification de l'alimentation dans la maladie rénale) le cas échéant (voir la rubrique 7.6.2 du protocole).
·des taux d'alanine aminotransférase (ALAT) et d'aspartate aminotransférase (ASAT) ≤ 2,5 x LSN. (Si une tumeur/des métastases hépatiques sont présentes, dans ce cas des taux < 5 x LSN sont autorisés).
6. Un statut de coagulation acceptable :
7. Avoir une espérance de vie d'au moins 3 mois.
D'autres critères d'inclusion se trouvent dans le protocole |
|
E.4 | Principal exclusion criteria |
1. Patients with primary neuroendocrine or sarcomatoid histologies.
2. Hematological: Known past or current coagulation defects leading to an increased risk of bleeding; diffuse alveolar hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; trauma with increased risk of life-threatening bleeding or history of severe head trauma or intracranial surgery within 8 weeks of trial entry.
3. Cardiovascular: Clinically significant cardiac disease including unstable angina, acute myocardial infarction 6 months prior to screening; any medical history of congestive heart failure (Grade III or IV as classified by the New York Heart Association, see Appendix G), any medical history of decreased cardiac ejection fraction of <45%.
4. Ophthalmological: Active ocular surface disease at baseline. An ocular evaluation is to be confirmed by an ophthalmologist at screening. Patients with any prior episode of cicatricial conjunctivitis or Steven Johnson syndrome (as evaluated by the investigator) are ineligible.
5. History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival ≥90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.
6. Lesions adjacent to or involving critical anatomical sites, including major blood vessels, mediastinum, and leptomeningeal disease.
7. Inflammatory bowel disease including Crohn’s disease and colitis ulcerosa.
8. Ongoing, acute or chronic inflammatory skin disease.
9. Uncontrolled tumor-related pain
10. Inflammatory lung disease, including moderate and severe asthma and chronic obstructive pulmonary disease, requiring chronic medical therapy
11. Medications or treatment regimens:
● For patients with SCCHN or NSCLC, therapeutic anti-coagulation is not permitted. For patients with colorectal or pancreatic cancers, therapeutic anti-coagulation therapy is permitted IF the patient is no longer being actively titrated for anti-coagulation. For oral anticoagulation therapy, colorectal and pancreatic patients must be on steady doses for at least 4 weeks prior to the first dose of study drug.
● Chronic prophylactic treatment with ASA (e.g., aspirin) in combination with other anti-coagulation therapy is prohibited.
● Cumulative dose of corticosteroid ≥150 mg (prednisone or equivalent doses of corticosteroids) within 2 weeks of the first tisotumab vedotin administration is prohibited.
12. Surgery/procedures: Major surgical procedure (defined as a surgery requiring inpatient hospitalization of at least 48 hours) within 4 weeks or excisional biopsy within 7 days prior to the first study drug administration. Patients who have planned major surgery during the treatment period must be excluded from the trial.
13. Received a live vaccine within 30 days prior to the first dose of trial treatment. 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, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
14. Peripheral neuropathy Grade ≥2.
15. Patients with clinical symptoms or signs of gastrointestinal obstruction and who require parental hydration and/or nutrition.
16. Prior therapy:
● Any prior treatment with MMAE-derived drugs.
● Radiotherapy within 21 days prior to the first administration of study drug. Patients must have recovered from all radiation-related toxicities. At least 42 days must have elapsed from the last administration of chemo-radiotherapy.
● Small molecules, chemotherapy, immunotherapy, biologics, experimental agents, or any other antitumor therapy within 21 days prior to the first administration of study drug. If underlying disease is progressing on treatment, patients may enroll within 21 days upon approval of the sponsor’s medical monitor. Patients must have recovered from all related toxicities.
17. Any uncontrolled Grade 3 or higher (per the NCI CTCAE v5.0) viral, bacterial, or fungal infection within 2 weeks prior to the first dose of tisotumab vedotin. Routine antimicrobial prophylaxis is permitted.
18. Known seropositivity of human immunodeficiency virus; known medical history of hepatitis B or C infection.
● Note: No testing for human immunodeficiency virus, Hepatitis B, or Hepatitis C is required unless mandated by local health authorities.
Other exclusion Criteria can be found in the Protocol. |
1.Patients présentant des histologies neuroendocrines ou sarcomatoïdes primaires.
2.Hématologique : Troubles de la coagulation connus passés ou actuels entraînant un risque accru de saignements ; hémorragie alvéolaire diffuse due à une vascularite ; diathèse hémorragique connue ; saignements importants en cours ; traumatisme avec risque accru d'hémorragie menaçant le pronostic vital ou antécédents de traumatisme crânien sévère ou de chirurgie intracrânienne dans les 8 semaines précédant l'entrée dans l'essai.
3.Cardiovasculaire : Cardiopathie significative sur le plan clinique, y compris angine instable, infarctus aigu du myocarde 6 mois avant la sélection ; antécédents médicaux d'insuffisance cardiaque congestive (grade III ou IV selon la classification de la New York Heart Association, voir l'annexe G du protocole), antécédents médicaux de diminution de la fraction d'éjection cardiaque de < 45 %.
4.Ophtalmologique : Maladie active de la surface oculaire à l'inclusion. Une évaluation oculaire doit être confirmée par un ophtalmologue lors de la sélection. Les patients ayant déjà présenté un épisode de conjonctivite cicatricielle ou de syndrome de Steven Johnson (évalué par l'investigateur) ne sont pas éligibles.
5.Antécédents d'une autre tumeur maligne dans les 3 ans précédant la première administration du médicament à l'étude, ou tout signe de maladie résiduelle d'une tumeur maligne diagnostiquée précédemment. Les exceptions sont les tumeurs malignes présentant un risque négligeable de métastases ou de mortalité (p. ex., survie globale à 5 ans ≥ 90 %), telles qu'un carcinome in situ du col de l'utérus, un carcinome cutané autre qu'un mélanome, un cancer de la prostate localisé, un carcinome canalaire in situ, ou un cancer de l'utérus de stade 1 traité de manière adéquate.
6.Lésions adjacentes à ou impliquant des sites anatomiques critiques, y compris les gros vaisseaux sanguins, le médiastin et une maladie leptoméningée.
7.Maladies inflammatoires de l'intestin y compris la maladie de Crohn et la rectocolite hémorragique.
8.Maladie inflammatoire en cours, aiguë ou chronique de la peau.
9.Douleurs non contrôlées liées à la tumeur
10.Maladie pulmonaire inflammatoire, y compris asthme modéré et sévère et bronchopneumopathie chronique obstructive, nécessitant un traitement médical chronique
11.Médicaments ou schémas de traitement :
• Pour les patients atteints d'un CPNPC ou d'un CETC, un traitement anti-coagulant n'est pas autorisé. Pour les patients atteints d'un cancer colorectal ou de cancers du pancréas, un traitement anti-coagulant est autorisé si la dose d'anti-coagulant du patient n'est plus ajustée de manière active. Pour le traitement anticoagulant par voie orale, les patients atteints d'un cancer colorectal et les patients atteints d’un cancer du pancréas doivent recevoir des doses stables depuis au moins 4 semaines avant la première administration du médicament à l'étude.
·Un traitement prophylactique chronique par ASA (p. ex., aspirine) en association avec un autre traitement anti-coagulant est interdit.
·Une dose cumulée de corticostéroïdes (prednisone ou doses équivalents de corticostéroïdes) ≥ 150 mg dans les 2 semaines précédant la première administration du vedotin tisotumab est interdite.
12.Chirurgie/procédures : Intervention chirurgicale lourde (définie comme une intervention chirurgicale nécessitant une hospitalisation d'au moins 48 heures) dans les 4 semaines ou une biopsie excisionnelle dans les 7 jours précédant la première administration du médicament à l'étude. Les patients qui ont planifié une chirurgie lourde pendant la période de traitement doivent être exclus de l'essai.
13.Avoir reçu un vaccin vivant dans les 30 jours précédant la première administration du traitement à l'essai. Des exemples de vaccins vivants comprennent, mais sans s'y limiter, ce qui suit : vaccin contre la rougeole, les oreillons, la rubéole, la varicelle/le zona, la fièvre jaune, la rage, le bacille de Calmette-Guérin, et la typhoïde. Les vaccins injectables contre la grippe saisonnière sont généralement des vaccins à virus inactivés et sont autorisés ; cependant, les vaccins contre la grippe administrés par voie nasale (p. ex., FluMist®) sont des vaccins vivants atténués et ne sont pas autorisés.
14.Neuropathie périphérique de grade ≥ 2.
D'autres critères d'exclusion se trouvent dans le protocole |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Investigator-determined confirmed ORR as measured by RECIST v1.1 |
TRO confirmé déterminé par l'investigateur à l'aide de RECIST v1.1 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
According to protocol. |
Selon le protocole. |
|
E.5.2 | Secondary end point(s) |
- Safety and tolerability of tisotumab vedotin, as measured by type, incidence, severity, seriousness, and relatedness of AEs
- Investigator-determined confirmed and unconfirmed ORR as measured by RECIST v 1.1
- Investigator-determined disease control rate (DCR) as measured by RECIST v1.1
- Investigator- determined duration of response (DOR) as measured by RECIST v1.1
- Investigator- determined time to response (TTR) as measured by RECIST v1.1
- Investigator- determined PFS as measured by RECIST v1.1
- Overall survival (OS)
- Selected PK parameters for tisotumab vedotin and MMAE
- Incidence of anti-therapeutic antibodies (ATAs) to tisotumab vedotin |
·Évaluer la sécurité d'emploi et la tolérance du tisotumab vedotin mesurées en fonction du type, de l'incidence, de la sévérité, de la gravité, et de l'interdépendance des événements indésirables (EI)
·Évaluer l'activité antitumorale préliminaire du tisotumab vedotin mesurée par le TRO confirmé et non confirmé
·Évaluer la stabilité et le contrôle de la maladie mesurés par le taux de contrôle de la maladie (TCM)
·Évaluer la durabilité de la réponse mesurée par la durée de la réponse (DR)
·Évaluer le moment de la réponse mesuré par le temps écoulé jusqu'à la réponse (TER)
·Évaluer la survie sans progression (SSP)
·Évaluer la survie mesurée par la survie globale (SG)
·Évaluer la pharmacocinétique (PK) et l'immunogénicité du tisotumab vedotin Supplémentaires :
·Évaluer la relation entre l'expression et la réponse du facteur tissulaire (TF)
·Évaluer les biomarqueurs de l'activité biologique et de la résistance et les biomarqueurs prédictifs de la réponse |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
According to protocol. |
Selon le protocole. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | 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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Germany |
Italy |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial 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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 24 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |