| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Stage III (Unresectable) or IV Melanoma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| 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 |
To compare OS in patients with previously untreated Stage IIIc, N3 (unresectable) or Stage IV melanoma receiving dacarbazine plus 10mg/kg ipilimumab vs. dacarbazine with placebo.
|
|
| E.2.2 | Secondary objectives of the trial |
1) To compare PFS between two arms;
2) To compare disease control rate (proportion with best overall response of CR or PR or SD) between two arms;
3) To compare BORR between two arms;
4) To estimate survival rates at 1 year, 18 months and 2 years for each treatment arm;
5) To estimate duration of response for each treatment arm;
6) To estimate time to response for each treatment arm;
7) To evaluate the safety profile for each treatment arm;
8) To evaluate HRQoL for each treatment arm;
9) To obtain serum samples for population PK.
Extension Phase Objectives
1) To estimate survival rates at 3, 4 and 5 years for ipilimumab;
2) To evaluate the safety profile of ipilimumab for patients in the
Extension Phase. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Willing and able to give written informed consent;
2) Histologic diagnosis of malignant melanoma;
3) Untreated unresectable Stage III melanoma with N3 macroscopic lymph nodes or
in-transit/satellite metastases or Stage IV melanoma (AJCC 2001) (note that prior
adjuvant melanoma therapy is permitted [e.g., IFN therapy]);
4) Measurable/evaluable disease (as per modified WHO criteria), within 28 days of first dose of study drug;
5) Life expectancy of ≥ 16 weeks;
6) ECOG performance status of 0 or 1 (see Protocol Appendix 3);
7) Have the complete set of baseline (i.e., Screening) digital images of lesions and
radiographic images, including, but not limited to: brain, chest, abdomen pelvis and
bone scans. All images must be of adequate quality;
8) Required values for initial laboratory tests:
• WBC ≥ 2500/uL
• ANC ≥ 1000/uL
• Platelets ≥ 75 x 103/uL
• Hemoglobin ≥ 9 g/dL
• Creatinine ≤ 2.5x ULN
• AST ≤ 3 x ULN for patients without liver metastasis ≤ 5 x ULN for patients with liver metastasis
• Bilirubin ≤ 3x ULN, (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/dL;
9) Negative Screening tests for HIV, HepB, and HepC. If positive results are not
indicative of true active or chronic infection, the patient can enter the study after
discussion and agreement between the Investigator and the CRO Medical Monitor;
10) Accessible for treatment and Follow-Up;
11) Men and women > 18 years of age (or, ≥ 16, if allowable per local regulatory
authority).
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity
25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication. |
|
| E.4 | Principal exclusion criteria |
1) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study.
2) Women who are pregnant or breastfeeding
3) Women with a positive pregnancy test on enrollment or prior to study drug
administration.
4) Sexually active fertile men whose partners are WOCBP, unless using an adequate
method of birth control
5) Evidence of brain metastases on brain imaging (i.e., MRI or contrast CT);
6) Any other malignancy from which the patient has been disease-free for less than
5 years, with the exception of adequately treated and cured basal or squamous cell
skin cancer, superficial bladder cancer or carcinoma in situ of the cervix;
7) Primary ocular or mucosal melanoma;
8) Autoimmune disease: Patients with a documented history of inflammatory bowel
disease, including ulcerative colitis and Crohn’s disease are excluded from this study
as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis,
systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus,
autoimmune vasculitis [e.g., Wegener’s Granulomatosis]);
9) Any underlying medical or psychiatric condition, which in the opinion of the
Investigator, will make the administration of study drug hazardous or obscure the
interpretation of AEs, such as a condition associated with frequent diarrhea;
10) Prior or concomitant therapy with any anti-cancer agent, immunosuppressive agents, surgery or radiotherapy (except as defined in Sections 6.2.8.3 and 6.2.8.4 of the protocol); other
investigational anti-cancer therapies, or chronic use of systemic corticosteroids (used
in the management of cancer or non-cancer-related illnesses). Prior adjuvant therapy
is not exclusionary;
11) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 4 weeks prior to or after any dose of ipilimumab or dacarbazine);
12) Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist;
13) Previous participation in another ipilimumab (MDX-010) clinical trial;
14) Treatment with other investigational products within the last 4 weeks prior to
randomization into this study;
15) Prisoners or patients who are compulsorily detained |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Time Frame: Patient Status is assessed at every visit (Weeks 1, 4, 7, 10, 12, 13, 16, 19, 20, 22, 24 in the Induction Phase, Weeks 24, 30, 36, 42, 48 and every 12 weeks thereafter in the Maintenance Phase, and every 12 weeks in the Follow-up Phase) |
|
| E.5.2 | Secondary end point(s) |
Progression-free survival [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ]
Disease Control Rate [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ]
Best Overall Response Rate [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ]
Survival rate at one year, eighteen months, and two years [ Time Frame: Patient Status is assessed at every visit (Weeks 1, 4, 7, 10, 12, 13, 16, 19, 20, 22, 24 in the Induction Phase, Weeks 24, 30, 36, 42, 48 and every 12 weeks thereafter in the Maintenance Phase, and every 12 weeks in the Follow-up Phase) ]
Duration of response [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ]
Time to Response [ Time Frame: Tumor Assessments at Baseline Visit in the Screening Phase, Wks 12, 16, 20, & 24 in Induction Phase, Wks 30, 36, 42, 48, & every 12 wks thereafter in Maintenance Phase, & the first two standard- of-care scans are collected in Follow-up Phase ]
Safety Profile [ Time Frame: Adverse Events are assessed at every visit (Weeks 1, 4, 7, 10, 12, 13, 16, 19, 20, 22, 24 in the Induction Phase, Weeks 24, 30, 36, 42, 48 and every 12 weeks thereafter in the Maintenance Phase, and every 12 weeks in the Follow-up Phase) ]
Health-Related Quality of Life [ Time Frame: QoL assessments are performed at Weeks 1, 4, 7, 12, 24, 36, 48, and at the first follow-up phase visit ]
Population PK [ Time Frame: PK samples are collected at Weeks 1, 7, 7 to 8, 8 to 9, and 10 ] |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | No |
| 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 | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Health-related quality of life (HRQoL) |
|
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 64 |
| 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 |
| Argentina |
| Australia |
| Austria |
| Belgium |
| Brazil |
| Canada |
| Chile |
| Czech Republic |
| France |
| Germany |
| Hungary |
| Ireland |
| Israel |
| Italy |
| Netherlands |
| Norway |
| Peru |
| Poland |
| Portugal |
| Russian Federation |
| South Africa |
| Spain |
| Switzerland |
| Ukraine |
| United Kingdom |
| United States |
|
| 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
|
This study will remain open until 5-year survival data on the last
patient has been obtained or the study is otherwise terminated by the
Sponsor. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 7 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 7 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
