A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers
21 Years
N/A
Both
Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma, Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers
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.
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
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
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)
Outcome Time Frame:
Up to 28 days
Safety Issue:
Yes
Principal Investigator
Keith Flaherty
Investigator Role:
Principal Investigator
Investigator Affiliation:
Abramson Cancer Center of the University of Pennsylvania
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02564
NCT ID:
NCT00074308
Start Date:
October 2003
Completion Date:
Related Keywords:
- Recurrent Melanoma
- Stage III Melanoma
- Stage IV Melanoma
- Unspecified Adult Solid Tumor, Protocol Specific
- Melanoma
Name | Location |
|---|---|
| Abramson Cancer Center of the University of Pennsylvania | Philadelphia, Pennsylvania 19104-4283 |
