Biochemotherapy and Bevacizumab Followed by Consolidation Therapy With Ipilimumab for Metastatic Melanoma

Study Overview
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Brief Summary
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A phase I-II study of treatment of metastatic melanoma using induction therapy with Biochemotherapy plus Bevacizumab followed by consolidation therapy with Ipilimumab (BBI).

Detailed Description
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A phase I-II study of treatment of metastatic melanoma using induction therapy with Biochemotherapy (Temodar,Cisplatin, Velban,IL2 and IFN)plus Bevacizumab followed by consolidation therapy with Ipilimumab (BBI)

Official Title
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A Phase I-II Study of Treatment of Metastatic Melanoma Using Induction Therapy With Biochemotherapy and Bevacizumab Followed by Consolidation Therapy With Ipilimumab (BBI)

Conditions
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Metastatic Melanoma

Intervention / Treatment
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* Drug: Biochemo + bevacizumab then ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Stage 4 or unresectable stage 3 metastatic melanoma with or without measurable disease Age 18-70 years old Adequate pulmonary and cardiac function for high-dose IL-2 PS 0-2 Previous ipilimumab therapy will not exclude patients, but patients with previous ipilimumab will have separate efficacy analysis Exclusion Criteria: Brain metastases Creatinine > 2x ULN; bilirubin > 3, WBC < 3500, Platelets < 100,000, Hgb < 9 Another active malignancy Gastrointestinal tract metastases except rectal metastases or primary are allowable Previous therapy for metastatic disease with chemotherapy of duration over 3 months or with high-dose interleukin-2 History of colitis or autoimmune disease such as lupus or rheumatoid arthritis Bevacizumab-related contraindications: Hemoptysis or history of severe bleeding, uncontrolled hypertension, proteinuria with protein/creatinine ratio > 1, acute myocardial infarction within 6 months

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Biochemo + Bevacizumab then Ipilimumab<br>Single arm: Biochemotherapy with 4 cycles at 3 week intervals of Temozolamide 150mg/m2 x4, cisplatin 20mg/m2 x 4, vinblastine 1.2mg/m2 x 4, bevacizumab 7.5-15 mg/kg x 1, interferon 5mg/m2 x5 and aldesleukin 36,18,9, % 9 miu/day over 4 days each cycle; then ipilimumab 3mg/kg q 21 days x 4, then q 3 months x 8 for total 3 years. | Drug: Biochemo + bevacizumab then ipilimumab<br>* Bevacizumab 7.5mg/kg week 1,repeat weeks 4,7,10 (cycles 2, 3, & 4)<br>* Other names: Yervoy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A phase I-II study of treatment of metastatic melanoma using induction therapy with Biochemotherapy and Bevacizumab followed by consolidation therapy with Ipilimumab (BBI) | Determine the incidence of grade 4 bevacizumab-related toxicities and grade 3 proteinuria when bevacizumab is given with biochemotherapy to patients with metastatic melanoma for up to 3 years. | Primary Objective | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A phase I-II study of treatment of metastatic melanoma using induction therapy with Biochemotherapy and Bevacizumab followed by consolidation therapy with Ipilimumab (BBI) | Compare median and overall progression-free survival to previously published historical control group of 135 patients receiving biochemotherapy followed by pulse IL-2, and also patients in the study of Weber et al (Reference 9) of ipilimumab in previously untreated patients for up to 4 years. | Secondary Objective |