| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Malignant Melanoma |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027480 |
| E.1.2 | Term | Metastatic malignant melanoma |
|
| 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 |
| The primary objective is to determine the progression-free survival (PFS) of patients with metastatic malignant melanoma who have not received prior chemotherapy for metastatic disease when treated with IMC-1121B alone or in combination with dacarbazine. |
|
| E.2.2 | Secondary objectives of the trial |
The secondary objectives will be to:
• Assess the safety and tolerability of IMC-1121B alone and in combination with dacarbazine
• Measure overall response rate (ORR)
• Determine median duration of response
• Measure stable disease rate at 6 weeks and 12 weeks
• Determine 12-week response rate
• Assess the pharmacokinetics of IMC-1121B alone and in combination with dacarbazine
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. The patient has histologically or cytologically confirmed cutaneous malignant melanoma that is American Joint Committee on Cancer (AJCC) stage IV (metastatic).
2. The patient is ≥ 18 years of age.
3. The patient has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-1.
4. The patient has completed any prior radiotherapy, biologic/immunotherapy or vaccine therapy (for adjuvant or advanced disease) at least 6 weeks prior to the first dose of study therapy.
5. The patient has a life expectancy > 3 months.
6. The patient has evidence of measurable disease as defined by RECIST.
7. The patient has resolution of all clinically significant toxic effects of prior cancer therapy to grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCI-CTCAE).
8. The patient has adequate hematological functions (absolute neutrophil count [ANC] ≥ 1500 cells/μL, hemoglobin ≥ 9 g/dL and platelets ≥ 100,000 cells/μL).
9. The patient has adequate hepatic function (bilirubin within normal limits [WNL], aspartate transaminase [AST] and/or alanine transaminase [ALT] ≤ 3.0 times the upper limit of normal [ULN], or ≤ 5.0 times the ULN if the transaminase elevation is due to liver metastases).
10. The patient has serum creatinine ≤ 1.5 x ULN (or a calculated creatinine clearance > 60 mL/min).
11. The patient’s urinary protein ≤ 1+ on dipstick or routine urinalysis ([UA]; if urine dipstick or routine analysis is ≥ 2+, a 24-hour urine for protein must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study).
12. The patient must have adequate coagulation function as defined by International Normalized Ratio (INR) ≤ 1.5 and a partial thromboplastin time (PTT) ≤ 1.5 X ULN. Patients on full-dose anticoagulation must be on a stable dose of oral anticoagulant or low molecular weight (LMW) heparin and if on warfarin must have a INR between 2 and 3 and have no active bleeding or pathological condition that carries a high risk of bleeding (eg, tumor involving major vessels or known varices).
13. The patient is able to provide informed written consent.
14. The patient, if sexually active, must be post-menopausal (last menstrual period > 2 years prior to study), surgically sterile, or is using an effective method of contraception in the opinion of the investigator.
|
|
| E.4 | Principal exclusion criteria |
1. The patient has mucosal or intra-ocular melanoma.
2. The patient has known or suspected brain or leptomeningeal metastases.
3. The patient has had prior cytotoxic chemotherapy for metastatic malignant melanoma.
4. The patient has had more than one line of biologic, immunologic, or vaccine-based therapy for metastatic malignant melanoma (not including adjuvant therapy).
5. The patient has a concurrent active malignancy other than adequately treated non-melanomatous skin cancer or other non-invasive carcinoma or in situ neoplasm. A patient with previous history of malignancy is eligible, provided that he/she has been disease free for > 3 years.
6. The patient has a nonhealing wound or ulcer.
7. The patient has a known alcohol or drug dependency.
8. The patient is pregnant or lactating.
9. The patient has a coexisting medical or psychiatric problem of sufficient severity to limit compliance with the study and/or increase the risks associated with study participation or study drug administration or interfere with the interpretation of study results.
10. The patient has an ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorders in the opinion of the investigator.
11. The patient has known human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness.
12. The patient has uncontrolled or poorly controlled hypertension despite standard medical management (>140 mmHg systolic or > 90 mmHg diastolic). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy endpoint for this study is PFS. PFS is defined as the time from the day of randomization to the first evidence of progression as defined by RECIST or death from any cause. Patients who die without a reported prior progression will be considered to have progressed on the day of their death. Patients who do not progress and are subsequently lost to follow-up will have their data censored at the day of their last tumor assessment.
The Kaplan-Meier method will be used to analyze PFS and to estimate the median survival time. The Kaplan-Meier survival curves will be presented as stratified. Log-rank test will be used to compare the survival curves for the stratification factors LDH status and extent-of-metastasis. The 95% confidence interval for the median survival time will be provided. A univariate Cox proportional hazards model analysis will be performed using treatment as a simple covariate and LDH status and extent of metastasis as strata. |
|
| 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 | No |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| 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 | Yes |
| 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) | Yes |
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.5.1 | Number of sites anticipated in the EEA | 1 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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