Imatinib Mesylate and Bevacizumab in Treating Patients With Advanced Melanoma or Other Advanced Cancers
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|ClinicalTrials.gov Identifier: NCT00074308|
Recruitment Status : Completed
First Posted : December 11, 2003
Results First Posted : January 16, 2018
Last Update Posted : January 16, 2018
|Condition or disease||Intervention/treatment||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|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers|
|Study Start Date :||October 2003|
|Actual Primary Completion Date :||July 2009|
|Actual Study Completion Date :||July 2009|
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
Other Names:Biological: bevacizumab
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
- 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 ]
- Progression-free Survival at 16 Weeks (Phase II) [ Time Frame: 16 weeks ]Progression Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
- Response Rate at 8 Weeks, Evaluated Using RECIST (Phase II) [ Time Frame: 8 weeks ]
Response and progression was evaluated in this study using Response Evaluation Criteria in Solid Tumors (RECIST).
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
- Overall Survival (Phase II) [ Time Frame: Up to 6 years ]Kaplan-Meier estimates of overall survival and 95% confidence intervals will be calculated.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00074308
|United States, Pennsylvania|
|Abramson Cancer Center of The University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|Principal Investigator:||Keith Flaherty||Abramson Cancer Center of the University of Pennsylvania|