Imatinib Mesylate and Bevacizumab in Treating Patients With Advanced Melanoma or Other Advanced Cancers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00074308
First received: December 10, 2003
Last updated: January 8, 2013
Last verified: December 2012
  Purpose

Phase II trial to study the effectiveness of combining imatinib mesylate with bevacizumab in treating patients who have advanced melanoma or other metastatic or unresectable cancer. Imatinib mesylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Bevacizumab may stop the growth of tumor cells by stopping blood flow to the tumor. Combining imatinib mesylate with bevacizumab may kill more tumor cells


Condition Intervention Phase
Recurrent Melanoma
Stage III Melanoma
Stage IV Melanoma
Unspecified Adult Solid Tumor, Protocol Specific
Drug: imatinib mesylate
Biological: bevacizumab
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers

Resource links provided by NLM:


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

Primary Outcome Measures:
  • MTD, defined as one dose level below the dose that induced DLT in at least one third of patients at a dose level, graded according to NCI CTCAE version 3.0 (Phase I) [ Time Frame: Up to 28 days ] [ Designated as safety issue: Yes ]
  • Progression-free survival at 8 weeks (Phase II) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    We will evaluate the percentage of patients who are progression-free at 8 weeks. Kaplan-Meier estimates of progression free survival and 95% confidence intervals will be calculated.


Secondary Outcome Measures:
  • Response rate at 8 weeks, evaluated using RECIST (Phase II) [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
    We will estimate response rates and 95% confidence intervals.

  • Overall survival (Phase II) [ Time Frame: Up to 6 years ] [ Designated as safety issue: No ]
    Kaplan-Meier estimates of overall survival and 95% confidence intervals will be calculated.


Enrollment: 64
Study Start Date: October 2003
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral imatinib mesylate once or twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: imatinib mesylate
Given orally
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OBJECTIVES:

I. Determine the tolerability, maximum tolerated dose, and lowest biologically active dose of imatinib mesylate and bevacizumab in patients with advanced melanoma or other advanced cancers.

II. Determine the response rate, time to progression, and survival of patients treated with this regimen.

III. Correlate clinical activity with inhibition of platelet-derived growth factor receptor beta, vascular endothelial growth factor receptor, flt-1, and markers of angiogenesis in patients treated with this regimen.

IV. Correlate clinical activity with alterations in tumor perfusion as assessed by dynamic contrast-enhanced MRI and Doppler ultrasound in patients treated with this regimen.

V. Correlate toxicity, clinical activity, and correlative endpoints with the steady-stage plasma concentration of imatinib mesylate in patients treated with this regimen.

OUTLINE: This is a dose-escalation, open-label study.

PHASE I (closed to accrual as of 8/23/04): Patients receive oral imatinib mesylate once or twice daily on days 1-28 and bevacizumab IV over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of imatinib mesylate and bevacizumab until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

PHASE II: Patients receive imatinib mesylate and bevacizumab as in phase I at the MTD.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of 1 of the following:

    • Metastatic or unresectable malignancy for which standard curative or palliative measures do not exist or are no longer effective (phase I) (phase I study closed to accrual as of 8/23/04)
    • Melanoma (phase I and II)
  • Measurable disease (phase II)
  • No history or clinical evidence of CNS disease, including primary brain tumor or brain metastases
  • Performance status - ECOG 0-1
  • More than 3 months
  • WBC at least 3,000/mm^3
  • Absolute granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No history of bleeding diathesis or coagulopathy
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST and ALT no greater than 2.5 times ULN
  • INR no greater than 1.5
  • APTT normal
  • Creatinine no greater than 2.0 times ULN
  • Creatinine clearance at least 40 mL/min
  • No proteinuria
  • Urinary protein less than 500 mg/24 hours
  • No history of stroke
  • No uncontrolled hypertension within the past 6 months

    • Blood pressure less than 150/100 mm Hg on a stable antihypertensive regimen
  • None of the following within the past 6 months:

    • Myocardial infarction
    • Unstable angina
    • New York Heart Association class II-IV congestive heart failure
    • Serious cardiac arrhythmia requiring medication
    • Grade II or greater peripheral vascular disease
    • Transient ischemic attack
    • Cerebrovascular accident
    • Other arterial thromboembolic event
    • Other clinically significant cardiovascular disease
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 3 months after study participation
  • No seizures not controlled with standard medical therapy
  • No prior allergic reactions attributed to Chinese hamster ovary cell products, other recombinant human antibodies, or compounds of similar chemical or biological composition to imatinib mesylate
  • No serious, nonhealing wound, ulcer, or bone fracture
  • No ongoing or active infection requiring parenteral antibiotics
  • No significant traumatic injury within the past 28 days
  • No psychiatric illness or social situation that would preclude study compliance
  • No other concurrent uncontrolled illness
  • More than 4 weeks since prior immunotherapy
  • More than 8 weeks since prior monoclonal antibody therapy
  • No concurrent prophylactic granulocyte or platelet colony-stimulating factors
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • No more than 1 prior cytotoxic chemotherapy regimen for advanced disease (phase II)
  • More than 4 weeks since prior radiotherapy
  • More than 28 days since prior major surgical procedure or open biopsy
  • Recovered from prior therapy
  • No concurrent chronic daily aspirin (greater than 325 mg/day) or nonsteroidal anti-inflammatory drugs known to inhibit platelet function
  • No recent or concurrent full-dose anticoagulants (except as required to maintain patency of preexisting permanent indwelling IV catheters) or thrombolytic agent
  • No concurrent grapefruit juice
  • No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent investigational or commercial agents or therapies directed at the malignancy
  • No other concurrent investigational agents
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00074308

Locations
United States, Pennsylvania
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Investigators
Principal Investigator: Keith Flaherty Abramson Cancer Center of the University of Pennsylvania
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00074308     History of Changes
Other Study ID Numbers: NCI-2012-02564, 03903, CDR0000343804
Study First Received: December 10, 2003
Last Updated: January 8, 2013
Health Authority: United States: Food and Drug Administration

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
Antibodies
Antibodies, Monoclonal
Imatinib
Bevacizumab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014