E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of unresectable stage III or IV melanoma. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027156 |
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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 evaluate the Best Objective confirmed Response Rate BORR , as per modified WHO criteria . |
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E.2.2 | Secondary objectives of the trial |
To evaluate the following in this patient population 1 To estimate disease control rate best response of CR PR SD ; 2 To estimate progression free survival PFS ; 3 To estimate overall survival OS ; 4 To estimate duration of best objective response and to evaluate the proportion of patients whose duration of response is 8805; 6 months; 5 To estimate time to best objective response; 6 To evaluate the safety profile of MDX-010 BMS-734016 during induction and maintenance; 7 To evaluate health-related quality of life HRQoL ; 8 To obtain PK samples for population PK analysis; 9 To evaluate the performance of candidate predictive markers as defined by other ongoing and/or planned MDX-010 BMS-734016 studies using paraffin-embedded tumor tissue from the original diagnostic biopsy. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Signed written informed consent 1 Willing and able to give written informed consent; Target population 2 Histologic diagnosis of malignant melanoma; 3 Measurable, unresectable Stage III or IV melanoma; 4 Patient must have progressed during or after at least one prior therapy containing at least one of the following dacarbazine, paclitaxel, carboplatin, fotemustine, or temozolamide. 5 At least 4 weeks since treatment chemotherapy, biochemotherapy, surgery, radiation, immunotherapy, etc. , for melanoma and recovered from any clinically significant toxicity experienced during treatment; 6 Life expectancy 8805; 4 months; 7 ECOG performance status of 0 or 1 see Appendix 4 ; 8 Required values for initial laboratory tests WBC 8805; 2500/uL ANC 8805; 1500/uL Platelets 8805; 100 x 103/uL Hemoglobin 8805; 10 g/dL Hematocrit 8805; 30 Creatinine 8804; 2 x ULN AST 8804; 2 x ULN Bilirubin 8804; 2 x ULN, except patients with Gilbert s Syndrome, who must have a total bilirubin less than 3.0 mg/mL; 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. Age and Sex 10 Men and women 8805; 18 years of age; Women of childbearing potential WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study in such a manner that the risk of pregnancy is minimized. Date 01-Jul-2005 55 Approved v1.0 930011454 1.0 MDX-010 CA184008 BMS-734016 Clinical Protocol WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization hysterectomy, bilateral tubal ligation or bilateral oophorectomy or is not postmenopausal defined as amenorrhea 8805; 12 consecutive months; or women on hormone replacement therapy HRT with documented serum follicle stimulating hormone FSH level 35 IU/mL . Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods diaphragm, condoms, spermacides to prevent pregnancy or practicing abstinence or where partner is sterile e.g. vasectomy , should be considered to be of childbearing potential. 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. |
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E.4 | Principal exclusion criteria |
Any of the following criteria will disqualify the patient from participation Sex and Reproductive Status 1 WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire period of the study and for up to 8 weeks after the study; 2 WPCBP using a prohibited contraceptive method Not Applicable 3 Women who are pregnant or breastfeeding; 4 Women with a positive pregnancy test at enrollment or prior to study drug administration; 5 Sexually active fertile men whose partners are WOCBP, unless using an adequate method of birth control; Target Disease Exceptions 6 Any other malignancy form 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, carcinoma in situ of the cervix; 7 Ocular melanoma; Medical History and Concurrent Disease 8 Active, symptomatic or asymptomatic untreated central nervous system CNS metastasis including metastasis identified incidentally during screening MRI or contrast CT ; 9 Prior treatment with an anti-CTLA4 antibody; Date 01-Jul-2005 56 Approved v1.0 930011454 1.0 MDX-010 CA184008 BMS-734016 Clinical Protocol 10 Autoimmune disease Patients with a history of Inflammatory Bowel Disease are excluded from this study as are patients with a history of autoimmune disease e.g. Systemic Lupus Erythematosus, vasculitis, infiltrating lung disease whose possible progression during treatment would be considered by the Investigator to be unacceptable. Patients with a history of well-controlled and/or clinically manageable autoimmune disease e.g. vitiligo, well-controlled thyroid disease, mild psoriasis may be considered for inclusion in consultation with the CRO; 11 Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea; Prohibited Therapies and/or Medications 12 Concomitant therapy with any of the following IL-2, interferon or other non-study anti-melanoma immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids used in the management of cancer or non-cancer-related illnesses ; 13 Previous treatment with other investigational products within 30 days; 14 Previous enrollment in another MDX-010 BMS-734016 clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist; Other Exclusion Criteria 15 Inability to provide adequate informed consent; 16 Prisoners or patients who are compulsorily detained involuntarily incarcerated for treatment of either a psychiatric or physical e.g., infectious disease illness must not be enrolled in this study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the Best Objective confirmed Response Rate BORR , as per modified WHO criteria . To evaluate the following in this patient population 1 To estimate disease control rate best response of CR PR SD ; 2 To estimate progression free survival PFS ; 3 To estimate overall survival OS ; 4 To estimate duration of best objective response and to evaluate the proportion of patients whose duration of response is 8805; 6 months; 5 To estimate time to best objective response; 6 To evaluate the safety profile of MDX-010 BMS-734016 during induction and maintenance; 7 To evaluate health-related quality of life HRQoL ; 8 To obtain PK samples for population PK analysis; 9 To evaluate the performance of candidate predictive markers as defined by other ongoing and/or planned MDX-010 BMS-734016 studies using paraffin-embedded tumor tissue from the original diagnostic biopsy. |
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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 | Information not present in EudraCT |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
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 | 2 |