Source: https://www.clinicaltrialsregister.eu/ctr-search/trial/2006-005978-51/GB
Timestamp: 2020-07-13 08:41:31
Document Index: 159525449

Matched Legal Cases: ['art 1', 'art 1', 'art 2', 'art 2', 'art 1', 'art 2', 'art 2', 'art 1', 'art 2', 'art 2']

EudraCT Number: 2006-005978-51
Sponsor's Protocol Code Number: TED6421
A.2 EudraCT number 2006-005978-51
A.4.1 Sponsor's protocol code number TED6421
D.3.2 Product code AVE1642
D.3.9.2 Current sponsor code AVE1642
D.3.11.13.1 Other medicinal product type Humanized version of the murine IgG1 monoclonal antibody muAVE1642 produced by recombinant CHO (Chinese Hamster Ovary) cells.
To select the dose of AVE1642 to be administered in patients with advanced solid tumors.
To confirm the selected dose (SD) when AVE1642 is given in combination with other anti-cancer agents. To assess the safety profile of AVE1642 as single agent and in combination with other anti-cancer agents. To define the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of AVE1642 when given as single agent and in combination in patients with advanced solid tumors. To detect any PK interaction between AVE1642 and the combined therapy. To assess the preliminary clinical activity of AVE1642 when added to other anticancer therapies in terms of response rate (RR), stable disease rate, duration of response and duration of stabilizations. To assess any potential immunogenicity by detection of anti-AVE1642 antibodies (HAHA). To assess the biological activity of AVE1642 on Circulating Tumoral Cells (CTC) and on tumor tissues when feasible.
TUMORAL TRANSCRIPTOME ANALYSIS SUB-STUDY Sub-study title: "Uncontrolled, multicenter, dose finding, safety and pharmacokinetic study of AVE1642, an anti-Insulin-like Growth Factor-1 Receptor (IGF-1R/ CD221) monoclonal antibody, administered as single agent and in combination with anticancer therapies in patients with advanced solid tumors" PROTOCOL ADDENDUM dated 5-July-2007, version 2.0 Sub-study objectives: This sub-study attempts to identify potential surrogate biomarkers associated to the biological effect of AVE1642 on tumor, and to identify any biological pathway/genes regulation associated to response to AVE1642 treatment.
Pathologically confirmed advanced-stage solid tumors Patients for whom the selected combined chemotherapy is indicated or is a reasonable option (as per tumor characteristics and previous treatments) ) and for whom the chemotherapy can be post-poned by 3 weeks in part 1 (during AVE1642 single treatment cycle) at the discretion of the Investigator: - docetaxel in part 1 - docetaxel or gemcitabine + erlotinib or doxorubicin in part 2. Written Informed Consent
< 15 years old in part 2 < 18 years old in part 1 and in part 2 in combination cohort C (gemcitabine + erlotinib) Eastern Cooperative Oncology Group (ECOG) performance status >2 (PS>2) Brain metastasis symptomatic or not More than two prior lines of chemotherapy (cytotoxic class) and no more than 4 prior lines of therapies (including molecular targeted agents) for advanced disease, in part 2 only Prior therapy with any IGF1 system targeting compound Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to study entry, or no recovery to grade < 1 from any prior therapy. Active infection or HIV disease requiring antiretroviral therapy HbA1c > 8% within 2 months prior to inclusion. Inadequate organ and bone marrow function as evidenced by: - Hemoglobin < 9.0 g/dL - Absolute neutrophil count < 1.5 x 10e9/L - Platelet count < 100 x 10e9/L - AST/SGOT and ALT/SGPT > 2.5 x ULN or > 5 x ULN in case of documented liver metastasis - Total bilirubin > 1.0 x ULN - Creatininemia > 1.5 x ULN or calculated creatinine clearance (CrCL) < 60ml/mn - Alkaline phosphatase (AP) > 2.5 x ULN Symptomatic peripheral neuropathy grade ≥ 2 (National Cancer Institute Common Terminology Criteria [NCI CTCAE] v3.0). Any of the following within 3 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, NYHA class III or IV congestive heart failure, cerebrovascular accident or transient ischemic attack, treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis, pulmonary embolism, or other uncontrolled thromboembolic event History of hypersensitivity to polysorbate 80 or to any of the drugs combined with AVE1642 Any contra-indication to the combined therapy considered (see the respective PIs/SmPCs of the combined therapies) Patient non postmenopausal or not surgically sterile, who doesn’t use effective contraception (the definition of effective contraception will be based on the judgement of the investigator and /or on the country requirement) Pregnancy or breastfeeding woman. Pregnancy tests not performed or not negative within the 7 days prior to registration In case of treatment with docetaxel or erlotinib, concurrent treatment with potent inhibitors/inducers of cytochrome P 450 3A4 is not allowed. For patients who are treated with such agents, a one-week washout period is required prior to study treatment administration. Other severe acute or chronic psychiatric or medical condition, or significant laboratory abnormality requiring further investigation that may cause undue risk for the patient’s safety, inhibit protocol participation, or interfere with interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study Absence of signed and dated approved patient informed consent form prior to enrollment into the study Patient unwilling and/or unable to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures . For the patients enrolled in the combination cohort with doxorubicin, cardiac function with LVEF (echocardiography or MUGA scan) ≤ 50%. An evaluation of the LVEF should have been performed within one month prior registration.
Primary endpoint : The selected dose will be a dose where plateaus of both clearance of AVE1642 and serum level of IGF-1 are concomitantly established, and where DLTs are not observed in ≥ 2 patients during AVE1642 administration as single agent and not in ≥ 3 patients in combination with docetaxel. Part 1 : When AVE1642 is administered alone at cycle 1, DLTs are AEs (whether related or not to the study drug, and if not in relation with documented progressive disease) defined as follows: 1. any grade ≥3 hematologic or non hematologic toxicity; 2. inability to resume the subsequent course within 14 days after the scheduled date, due to a study drug related AE. When AVE1642 is administered in combination with docetaxel at cycle 2, and based on the incidence and severity of the toxicities reported with docetaxel single agent at the dose of 75mg/m² in patients with advanced pretreated diseases, the following toxicities are considered as DLTs: Hematological toxicities: 1. Grade 3 or 4 neutropenia complicated by fever ≥ 38.5ºC(i.e., febrile neutropenia) or documented infection; 2. Grade 4 neutropenia > 7 days; 3. Grade 4 thrombocytopenia, or grade 3 thrombocytopenia complicated by hemorrhage. Non-hematological toxicities: 1. Grade 3 or 4 non-hematologic toxicities (except fatigue / asthenia < 2 weeks in duration, anorexia, nausea / vomiting in the absence of optimal anti-emetics, diarrhea inthe absence of optimal anti-diarrheals, alkaline steroid pre-medication, or alopecia, unless both the investigator and Sponsor conclude that such inclusion is necessary –e.g., if these AEs are excessive in frequency or duration, or required excessive use of supportive therapy); 2. Grade 3 or 4 peripheral sensory neuropathy, unless of ≤ 2 weeks duration, or both the investigator and Sponsor conclude that these AEs are not DLTs. In case of DLTs (as defined above), the decision on the study continuation will be discussed between the Sponsor and the Investigators.In the event of 1 DLT among the first 3 patients of the cohort, enrollment will be extended to include a total of 6 patients for that cohort. A total of 3 DLTs in that cohort will be considered as a stopping rule. Part 2 : The aim of part 2 is to confirm the feasibility of the selected combination treatments, primarily based on safety evaluation: incidence and severity of treatment emergent adverse events (TEAEs) / serious AE’s reported during the first cycle of the combination treatments will be assessed taking into account the expected safety profile of the combined anti-cancer agents when given in the same conditions without AVE1642.