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

A Phase I/II Study Of Imatinib Mesylate And Bevacizumab In Patients With Advanced Melanoma And Other Advanced Cancers

Status
Completed
Phases
Phase 1Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00074308
Enrollment
40
Registered
2003-12-11
Start date
2003-10-31
Completion date
2009-07-31
Last updated
2018-06-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Recurrent Melanoma, Stage III Melanoma, Stage IV Melanoma, Unspecified Adult Solid Tumor, Protocol Specific

Brief summary

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

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.

Interventions

DRUGimatinib mesylate

Given orally

BIOLOGICALbevacizumab

Given IV

OTHERpharmacological study

Correlative studies

OTHERlaboratory biomarker analysis

Correlative studies

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
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)Up to 28 days
Progression-free Survival at 16 Weeks (Phase II)16 weeksProgression 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.

Secondary

MeasureTime frameDescription
Response Rate at 8 Weeks, Evaluated Using RECIST (Phase II)8 weeksResponse 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)Up to 6 yearsKaplan-Meier estimates of overall survival and 95% confidence intervals will be calculated.

Countries

United States

Participant flow

Participants by arm

ArmCount
Phase 1
Patients receive oral imatinib mesylate once or twice daily (400-800 mg/day) on days 1-28 and bevacizumab IV (5-10mg/kg) over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
17
Phase 2
Patients receive oral imatinib mesylate once or twice daily (400 mg/day) on days 1-28 and bevacizumab IV (10mg/kg) over 30-90 minutes on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptance toxicity.
23
Total40

Baseline characteristics

CharacteristicPhase 1Phase 2Total
Age, Categorical
Arm 1
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
Arm 1
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Arm 1
Between 18 and 65 years
17 Participants23 Participants40 Participants
Region of Enrollment
United States
17 Participants23 Participants40 Participants
Sex: Female, Male
Arm 1
Female
4 Participants7 Participants11 Participants
Sex: Female, Male
Arm 1
Male
13 Participants16 Participants29 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
deaths
Total, all-cause mortality
0 / 30 / 30 / 30 / 82 / 23
other
Total, other adverse events
0 / 30 / 30 / 31 / 81 / 23
serious
Total, serious adverse events
0 / 30 / 30 / 31 / 81 / 23

Outcome results

Primary

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

ArmMeasureValue (NUMBER)
Phase 1 = Dose EscalationMTD, 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)2 dose level
Primary

Progression-free Survival at 16 Weeks (Phase II)

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.

Time frame: 16 weeks

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Phase 1 = Dose EscalationProgression-free Survival at 16 Weeks (Phase II)8 Participants
Secondary

Overall Survival (Phase II)

Kaplan-Meier estimates of overall survival and 95% confidence intervals will be calculated.

Time frame: Up to 6 years

Population: Data not collected

Secondary

Response Rate at 8 Weeks, Evaluated Using RECIST (Phase II)

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.

Time frame: 8 weeks

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
Phase 1 = Dose EscalationResponse Rate at 8 Weeks, Evaluated Using RECIST (Phase II)1 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026