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A Phase I and a Randomized Phase II Study of Maximal Angiogenic Blockade in Advanced Renal Carcinoma: Bevacizumab (NSC-704865) With or Without MEDI-522 (NSC-719850)


Phase 1/Phase 2
N/A
N/A
Not Enrolling
Both
Recurrent Renal Cell Cancer, Renal Cell Carcinoma, Stage III Renal Cell Cancer, Stage IV Renal Cell Cancer

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Trial Information

A Phase I and a Randomized Phase II Study of Maximal Angiogenic Blockade in Advanced Renal Carcinoma: Bevacizumab (NSC-704865) With or Without MEDI-522 (NSC-719850)


PRIMARY OBJECTIVES:

I. To assess the appropriate dose of bevacizumab when administered with humanized monoclonal
antibody MEDI-522 in patients with unresectable or metastatic renal cell carcinoma
previously treated with sunitinib malate or sorafenib tosylate. (Phase I) II. To compare the
progression-free survival of these patients treated with bevacizumab with versus without
humanized monoclonal antibody MEDI-522. (Phase II) III. To evaluate the qualitative and
quantitative toxicities of bevacizumab and humanized monoclonal antibody MEDI-522 in these
patients. (Phase II) IV. To estimate overall survival and RECIST response rate (i.e.,
confirmed and unconfirmed, complete and partial responses) in both treatment arms. (Phase
II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of bevacizumab followed by a
randomized phase II study.

PHASE I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and humanized
monoclonal antibody MEDI-522 IV on days 1, 8, 15, and 22. Courses repeat every 28 days in
the absence of disease progression or unacceptable toxicity until the recommended phase II
dose (RPTD) of bevacizumab is determined.

PHASE II: Patients are stratified according to the number of prior treatment regimens for
renal cell carcinoma (1 vs 2) and whether there is a clear cell component (yes vs no).
Patients are randomized to 1 of 2 treatment arms:

ARM I: Patients receive bevacizumab (10 mg/kg) IV over 30-90 minutes on days 1 and 15.

ARM II: Patients receive bevacizumab IV as in arm I at the RPTD determined in phase I, and
humanized monoclonal antibody MEDI-522 (8 mg/kg) IV over 30 minutes on days 1, 8, 15, and
22.

In both arms, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.

After completion of study therapy, patients are followed periodically for up to 3 years.

Inclusion Criteria


Criteria:

- Histologically or cytologically confirmed renal cell carcinoma

- Metastatic or unresectable disease

- Must have received prior sunitinib malate or sorafenib tosylate for metastatic or
unresectable disease

- Measurable disease

- No soft tissue disease that has been irradiated within the past 2 months

- More than 6 months since prior and no concurrent treated or untreated brain
metastases

- Stable, treated brain metastases allowed provided they remained stable for more than
6 months

- Patients with clinical evidence of brain metastases must have a negative brain CT or
MRI scan for metastatic disease

- Zubrod performance status 0-1

- Urine protein:creatinine ratio =< 0.5 OR urine protein < 1,000 mg by 24-hour
collection

- Not be pregnant or nursing

- Fertile patients must use effective contraception during and for at least 6 months
after completion of study therapy

- No serious or non-healing wound, ulcer, or bone fracture

- No clinically relevant bleeding diathesis or coagulopathy

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 28 days

- No significant traumatic injury within the past 28 days

- No known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

- No other prior malignancy, except adequately treated basal cell or squamous cell skin
cancer, carcinoma in situ of the cervix, adequately treated stage I or II cancer from
which the patient is currently in complete remission, or any other cancer from which
the patient has been disease-free for 5 years

- No New York Heart Association class II-IV congestive heart failure

- No unstable symptomatic arrhythmia requiring medication

- Chronic, controlled arrhythmias (e.g., atrial fibrillation or paroxysmal
supraventricular tachycardia) allowed

- None of the following cardiovascular conditions within the past 6 months: Arterial
thrombosis, Unstable angina, Myocardial infarction, Cerebrovascular accident

- Must have controlled blood pressure, defined as systolic blood pressure (BP) =< 160
mm Hg and/or diastolic BP =< 90 mm Hg

- More than 7 days since prior core biopsy

- At least 14 days since completion of prior therapy and recovered

- At least 28 days since prior radiotherapy and recovered

- No prior radiotherapy to >= 25% of bone marrow

- No more than two prior systemic regimens for renal cell carcinoma (including adjuvant
treatment)

- No prior bevacizumab or humanized monoclonal antibody MEDI-522

- No major surgical procedure or open biopsy within the past 28 days

- No concurrent need for a major surgical procedure

- Concurrent full-dose anticoagulation with warfarin allowed provided INR is between
2-3

- Concurrent low molecular weight heparin allowed

- No clinically significant vascular disease (e.g., aortic aneurysm or history of
aortic dissection)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose of bevacizumab , based on incidence of DLT graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I)

Outcome Time Frame:

Up to 8 weeks

Safety Issue:

Yes

Principal Investigator

Christopher Ryan

Investigator Role:

Principal Investigator

Investigator Affiliation:

Southwest Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-01099

NCT ID:

NCT00684996

Start Date:

June 2008

Completion Date:

Related Keywords:

  • Recurrent Renal Cell Cancer
  • Renal Cell Carcinoma
  • Stage III Renal Cell Cancer
  • Stage IV Renal Cell Cancer
  • Carcinoma
  • Carcinoma, Renal Cell

Name

Location

Presbyterian HospitalCharlotte, North Carolina  28233-3549
UC Davis Comprehensive Cancer CenterSacramento, California  95817
Fremont - Rideout Cancer CenterMarysville, California  95901
University of Michigan University HospitalAnn Arbor, Michigan  48109
Southwest Oncology GroupSan Antonio, Texas  78245