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

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00626405
First received: February 28, 2008
Last updated: November 29, 2012
Last verified: December 2009
  Purpose

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.


Condition Intervention Phase
Melanoma (Skin)
Biological: bevacizumab
Drug: carboplatin
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Drug: temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival at 6 months [ Designated as safety issue: No ]
  • Toxicity as measured by NCI CTCAE version 3.0 [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor response rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Percent change in number of T, B, NK and dendritic cells from baseline [ Designated as safety issue: No ]
  • Percent change in plasma concentrations of IL-1β, IL-1rα, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12(p70), IL-13, IL-15, IL-17, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF, RANTES, TNF-α, and VEGF from baseline [ Designated as safety issue: No ]
  • Immune response [ Designated as safety issue: No ]

Estimated Enrollment: 41
Study Start Date: August 2008
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral temozolomide on days 1-5 and bevacizumab IV over 30-90 minutes on days 1 and 15.
Biological: bevacizumab
Given IV over 30-90 minutes
Drug: temozolomide
Oral temozolomide on days 1-5
Experimental: 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.
Biological: bevacizumab
Given IV over 30-90 minutes
Drug: carboplatin
Given IV over 30 minutes
Drug: paclitaxel albumin-stabilized nanoparticle formulation
Given IV over 30 minutes

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologic confirmed diagnosis of malignant melanoma

    • Stage IV disease
    • Not amenable to surgery
  • Measurable disease with at least one lesion whose longest diameter can be 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

PATIENT CHARACTERISTICS:

Inclusion criteria:

  • 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 OR proteinuria < 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

Exclusion criteria:

  • Active infection requiring parenteral antibiotics
  • Poorly controlled high blood pressure (≥ 150 mm Hg systolic and/or 100 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 standard medical 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 CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00626405

  Show 259 Study Locations
Sponsors and Collaborators
North Central Cancer Treatment Group
Investigators
Study Chair: Svetomir Markovic, MD, PhD Mayo Clinic
  More Information

Additional Information:
Publications:
Responsible Party: Jan C. Buckner, North Central Cancer Treatment Group
ClinicalTrials.gov Identifier: NCT00626405     History of Changes
Other Study ID Numbers: CDR0000587708, NCCTG-N0775
Study First Received: February 28, 2008
Last Updated: November 29, 2012
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage IV melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Temozolomide
Dacarbazine
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on April 21, 2014