Patients with unresectable and metastatic (stage IIIc and stage IV) melanoma will be randomized to either treatment arm A (ipilimumab) or treatment arm B (TIL) after metastasectomy and feasibility of culturing of TIL. MedDRA version: 21.1 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma
Conditions
Interventions
Trade Name: Yervoy
Pharmaceutical Form: Infusion
INN or Proposed INN: IPILIMUMAB
Other descriptive name: Yervoy
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration
Sponsors
Antoni van Leeuwenhoek ziekenhuis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Histologically confirmed unresectable AJCC stage III or stage IV melanoma • Patients must have metastatic melanoma with a resectable metastatic lesion(s) of sufficient size (= 2-3 cm in total) and must be willing to undergo such a resection for experimental purposes. Resected metastases during stage IV disease that were removed at much earlier time points, but were used to grow clinical grade TIL up to Rapid Expansion Protocol may be used as well with informed consent of the patient. • Patients should have received no previous systemic therapy for unresectable or metastatic melanoma or one line of any kind of systemic treatment, except for ipilimumab.[Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to randomization,and all related adverse events have either returned to baseline or stabilized.] • Patients must be = 18 years and = 75 years of age and must have measurable disease by CT or MRI per RECIST 1.1 criteria (in addition to the resected lesion). • Patients must have a clinical performance status of ECOG 0 or 1. • Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen. • Patients must be able to understand and sign the Informed Consent document. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 144 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: • Life expectancy of less than three months. • Patients with metastatic ocular/ mucosal or other non-cutaneous melanoma. • Adjuvant treatment with ipilimumab within 6 months prior to randomization. • Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone or equivalent) or other immunosuppressive drugs within the last 3 weeks prior to randomization. • Patients who have a more than two CNS metastases. • Patients who have any CNS lesion that is symptomatic, greater than 1 cm in diameter or show significant surrounding edema on MRI scan will not be eligible until they have been treated and demonstrated no clinical or radiologic CNS progression for at least 2 months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: to compare progression free survival (according to RECIST 1.1) at 6 months between patients treated with ipilimumab as compared to patients treated with TIL therapy.;Secondary Objective: -Progression free survival (according to RECIST 1.1 and irRC). Overall response rate according RECIST version 1.1 and irRC, complete response rate, overall survival and safety (according to CTCAE v. 4.0). -To evaluate the impact of the TIL treatment on patient, organizational and economic consequences, a constructive technology assessment (CTA) will be performed. In this CTA, Health Related Quality of Life is evaluated using a questionnaire. Additionally, patient impact of receiving TIL treatment is evaluated by a semi-structured interview with patients receiving TIL treatment and finally the incremental costs per Quality Adjusted Life Year (QALY) gained will be estimated (cost-effectiveness).;Primary end point(s): The primary endpoint is progression free survival (according to RECIST 1.1) at 6 months.;Timepoint(s) of evaluation of this end point: After 6 months of follow-up of the last patient. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints are PFS (according RECIST to irRC), the overall response rate, complete response rate, overall survival and safety. Health Related Quality of Life is evaluated using a questionnaire. Additionally, patient impact of receiving TIL treatment is evaluated by a semi-structured interview with patients receiving TIL treatment and finally the incremental costs per Quality Adjusted Life Year (QALY) gained will be estimated (cost-effectiveness).;Timepoint(s) of evaluation of this end point: After 5 years of follow-up | — |
Countries
Denmark, Netherlands
Contacts
Public ContactBiometrics department
Antoni van Leeuwenhoek ziekenhuis
Outcome results
None listed