E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Previously Treated 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 | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025670 |
E.1.2 | Term | Malignant melanoma stage III |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025671 |
E.1.2 | Term | Malignant melanoma stage IV |
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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 estimate the anti-tumor activity of therapeutic vaccination with autologous TriMix-DC vaccine in combination with ipilimumab in patients with previously treated, therapy-refractory or -intolerant, unresectable, AJCC Stage III or Stage IV melanoma. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the safety profile of TriMix-DC and ipilimumab treatment during the Induction and Maintenance Phases. • Safety data will be collected on a continuous basis and will be reviewed by the Sponsor in order to ensure that it is appropriate to continue the study; • An interim safety analysis will be performed when the sixth patient has been followed up to Week 24 (: end of the ipilimumab induction phase); • Patient recruitment will be uninterrupted on a continuous basis unless the Sponsor, decides to interrupt patient recruitment because of safety concerns; To evaluate the percentage of best objective tumor response rate and stable disease according to immune related response criteria and mWHO criteria; Estimate the duration of best overall response Estimate the progression free survival rate at the Week 12 and 24 tumor evaluations Estimate the median progression free survival?median overall survival and survival rate at one year.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willing and able to give written informed consent; 2. Accessible for treatment and follow-up; 3. Histologically confirmed malignant melanoma; primary melanoma of the skin, or unknown primary site (patients with primary mucosa or uveal melanoma are not eligible). 4. Measurable melanoma, as per irRC criteria; 5. AJCC Stage III (unresectable) or Stage IV melanoma; 6. Patient must have demonstrated one of the following in response to treatment with at least one prior regimen (non-experimental or experimental) with the exception of a CD137 agonist or PD-1 or CTLA-4 inhibitor or agonist: a. relapse following an objective response of PR or CR; or b. failed to demonstrate an objective response of PR or CR based on an assessment period of at least 12 weeks from prior regimen start; or c. inability to tolerate treatment due to toxicity; 7. Have a complete set of baseline (i.e., Screening) digital images of lesions and radiographic images, including, but not limited to: brain, bone, chest, abdomen and pelvis. 8. Required values for initial laboratory tests: • WBC 2500/mm³ • ANC 1500/ mm³ • Platelets 75 x 103/uL • Hemoglobin 9 g/dL (may be transfused) • Creatinine 2.0 x ULN • AST/ALT 2.5 x ULN for patients without liver metastasis, 5 times for liver metastases • Bilirubin 2.0 x ULN, (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/dL) 9. No active or chronic infection with HIV, Hepatitis B, or Hepatitis C. 10. ECOG performance status of 0 or 1; 11. Life expectancy of > 16 weeks; 5.6.3 Age and Sex 12. Men and women, 18 years of age. The following paragraphs are mandatory when the protocol includes Women of Childbearing Potential. 13. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized. In general, the decision for appropriate methods to prevent pregnancy should be determined by discussions between the investigator and the study subject. 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 post-menopausal. Post-menopause is defined as: Amenorrhea 12 consecutive months without another cause, or For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level 35 mIU/mL. Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, 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 before the start of ipilimumab. Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized.
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E.4 | Principal exclusion criteria |
1. Evidence of brain metastases on brain imaging (i.e., MRI or contrast CT); 2. Primary ocular or mucosal melanoma; 3. 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 or carcinoma in situ of the cervix. 4. Autoimmune disease: Patients with a 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 (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener’s Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis). 5. Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea. 6. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab). 7. A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA 4 inhibitor or agonist, or PD-1 antagonist;. 8. Concomitant therapy with any of the following: IL 2, interferon, or other non-study 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); 9. Concomitant therapy with and need of uninterrupted therapeutic anticoagulation (e.g. because of a recent thrombo-embolic event or cardiac valve prothesis). 10. Previous treatment with other investigational products, including cancer immunotherapy, within 30 days preceding study recruitment; 11. Previous treatment in another ipilimumab clinical trial or prior treatment with a CD137 agonist, CTLA-4 inhibitor or agonist; 12. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness. 13. Women of childbearing potential (WOCBP), defined above in Section 4.1, who: - are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or - have a positive pregnancy test at baseline, or - are pregnant or breastfeeding. Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. Before study enrollment, WOCBP must be advised of the importance of avoiding pregnancy during study participation and the potential risk factors for an unintentional pregnancy. All WOCBP MUST have a negative pregnancy test before first receiving ipilimumab. If the pregnancy test is positive, the patient must not receive ipilimumab and must not be enrolled in the study. 14. Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this clinical trial is the disease control rate (DCR; the percentage of patients who have a complete or partial response or stable disease according to the immune-related response criteria (irRC) with the tumor evaluation on Week -2 as the baseline). |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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
| 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.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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It is anticipated that a maximum of 20 months of enrollment will be required to complete accrual. Recruitment Start Date (FPI): 01 Dec 2010 Recruitment End Date (LPI): 01 June 2012 The primary analysis will be performed when the last patient has been followed to Week 24. The end of the study will occur at the Week 24 visit of the last subject on study (LPFV +24 Weeks).
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |