Bevacizumab and Temozolomide or Bevacizumab and Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Carboplatin in Treating Patients With Stage IV Malignant Melanoma That Cannot Be Removed by Surgery

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Melanoma (Skin)

Treatments: Drug: temozolomide; Drug: paclitaxel albumin-stabilized nanoparticle formulation; Biological: bevacizumab; Drug: carboplatin

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00626405

NCCTG-N0775

NCI-2009-00667 (Registry Identifier)

CDR0000587708 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as temozolomide, paclitaxel albumin-stabilized nanoparticle formulation, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether bevacizumab is more effective when given together with temozolomide or paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in killing malignant melanoma cells.

PURPOSE: This randomized phase II trial is studying the side effects of giving temozolomide together with bevacizumab and to see how well it works compared with giving bevacizumab together with paclitaxel albumin-stabilized nanoparticle formulation and carboplatin in treating patients with stage IV malignant melanoma that cannot be removed by surgery.

Full description

OBJECTIVES:

Primary

• To assess the anti-tumor activity, in terms of the percentage of patients who are treated with these regimens and who are progression-free at 6 months.
• To assess the safety profile of each treatment regimen.

Secondary

• To estimate the response rate in patients treated with these regimens.
• To estimate the distribution of progression-free survival time and overall survival time of patients treated with these regimens.

Tertiary

• To examine the impact of therapy on angiogenesis and immune homeostasis.

OUTLINE: Patients are stratified according to ECOG performance status (0 vs 1) and location of metastatic disease (M1a [skin or subcutaneous tissue or lymph node only] vs M1b [lung] vs M1c [other visceral sites]) and randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15. (closed to accrual 8/21/09)
• Arm II: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.

In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Patients undergo blood sample collection periodically for VEGF plasma levels and analysis of changes in immune homeostasis.

Beginning at study entry, patients are followed up every 3 months for 2 years and then every 6 months for up to 3 years.

Enrollment: 95 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• Histologic confirmed diagnosis of malignant melanoma

  • Stage IV disease
  • Not amenable tosurgery

• Measurable disease with at least one lesion whose longest diameter canbe measured as ≥ 20 mm by CT or MRI scans OR ≥ 10 mm by spiral CT

  • No disease that is measurable by physical examination only

• No brain metastases per MRI or CT

• No radiographically documented invasion of adjacent organs(duodenum, stomach, etc.) or tumor invading major blood vessels

• ECOG performance status 0-1

• Life expectancy ≥ 4 months

• ANC ≥ 1,500/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL (transfusion allowed)

• Creatinine ≤ 1.5 times upper limit of normal (ULN)

• Total bilirubin ≤ 1.5 mg/dL (unless Gilbert syndrome)

• AST ≤ 2.5 times ULN

• Alkaline phosphatase ≤ 2.5 times ULN

• Urine protein:creatinine ratio < 1.0 at screening ORproteinuria < 2+ by urine dipstick or protein ≤ 1 g by 24-hour urine collection

• Negative serum pregnancy test

• Not pregnant or nursing

• Fertile patients must use effective contraception

• Active infection requiring parenteral antibiotics

• Poorly controlled high blood pressure (≥ 150 mm Hg systolic and/or100 mm Hg diastolic) despite treatment

• NYHA class II-IV congestive heart failure

• Serious cardiac arrhythmia requiring medication

• Myocardial infarction or unstable angina within the past 6 months

• Clinically significant peripheral vascular disease

• Deep venous thrombosis or pulmonary embolus within the past year

• Active bleeding or pathological conditions that carry high risk of bleeding (e.g., known esophageal varices)

• Serious, non-healing wound (including wounds healing by secondary intention), ulcer or bone fracture

• Abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within the past 6 months

• History of CNS disease (e.g., primary brain tumor, vascular abnormalities, etc.)

• Clinically significant stroke or TIA within the past 6 months

• Seizures not controlled with standardmedical therapy

• Peripheral neuropathy ≥ grade 2

• History of other malignancy within the past 5 years except basal cell or squamous cell carcinoma of the skin treatable with local resection only or carcinoma in situ of the cervix

• Significant traumatic injury within the past 4 weeks

• History of hypertensive crisis or hypertensive encephalopathy

• Active or recent (≤ 30 days) history of hemoptysis (≥ ½ teaspoon of bright red blood per episode)

• Known hypersensitivity to any of the components of bevacizumab

• Known to be HIV positive

• Current or known history of hepatitis

• Prior adjuvant chemotherapy and/or immunotherapy for this cancer allowed

• No prior treatment with agents disrupting VEGF activity (i.e., bevacizumab,VEGF-trap, anti-VEGFR Mab)

• No ongoing need for full-dose oral or parenteral anticoagulation

• No ongoing anti-platelet treatment other than low-dose aspirin(i.e., aspirin 81 mg daily)

• No other investigational agents within the past 4 weeks

• No major surgical procedure or open biopsy within the past 4 weeks

• No fine needle aspirations or core biopsies within the past 7 days

• No prior chemotherapy in the metastatic setting

• No prior treatment with sunitinib malate or sorafenib

• No prior treatment with any taxane-based chemotherapy

• Patients who have had > 25% of their functional bone marrow irradiated are not eligible for this trial

• No adjuvant radiation therapy within the past 4 weeks

• More than 2 weeks since prior and no concurrent palliative radiation therapy

• No concurrent major surgical procedure

• No concurrent participation in another clinical study for procedures or agents that treat the same primary study malignancy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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95 participants in 2 patient groups

Arm I

Experimental group

Description:

Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15.

Treatment:

Biological: bevacizumab

Drug: temozolomide

Arm II

Experimental group

Description:

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15, paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes on days 1, 8, and 15, and carboplatin IV over 30 minutes on day 1.

Treatment:

Drug: paclitaxel albumin-stabilized nanoparticle formulation

Biological: bevacizumab

Drug: carboplatin