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Recurrent MelanomaPhase 1/2NCT00074308

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

A Phase 1/2 study testing imatinib mesylate, bevacizumab and pharmacological study in people with Recurrent Melanoma and Stage III Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 years and older
What is being tested?
imatinib mesylate, bevacizumab and pharmacological study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
Oct 2003to Jul 2009
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 57Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Abramson Cancer Center of The University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

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

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

Read the detailed description

OBJECTIVES:

  1. 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.

  1. 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.

Being tested
imatinib mesylate, bevacizumab, pharmacological study, laboratory biomarker analysis
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • imatinib mesylateDrug

    Also called CGP 57148, Gleevec, Glivec

    Given orally

  • bevacizumabBiological

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00074308
Study groupRoleWhat they receive
Arm IExperimentalPatients 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.
Receives: Drug: imatinib mesylate; Biological: bevacizumab; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Up to 28 days

  2. 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.

    Measured: 16 weeks

Secondary outcomes (2)

  1. 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.

    Measured: 8 weeks

  2. Overall Survival (Phase II)

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

    Measured: Up to 6 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Dec 2003 (estimated)
  2. Study startOct 2003
  3. Primary completionJul 2009
  4. Study completionJul 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00074308
Sponsor's protocol ID
NCI-2012-02564
Other IDs
03903, CDR0000343804
Status last verified
May 2018
First submitted
10 Dec 2003
Last updated
20 Jun 2018

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing imatinib mesylate, bevacizumab and pharmacological study in people with Recurrent Melanoma and Stage III Melanoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 57 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary 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) (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00074308.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2018.

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