Bevacizumab With or Without MEDI-522 in Treating Patients With Unresectable or Metastatic Kidney Cancer

Renal Cell Carcinoma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00684996
• Other study ID #: NCI-2009-01099
• Secondary ID: NCI-2009-01099CD
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: May 24, 2008
• Last updated: April 28, 2014
• Start date: June 2008
• Est. completion date: October 2010

Study information

• Verified date: April 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This phase I/randomized phase II trial is studying the side effects and best dose of bevacizumab and to see how well it works when given together with or without MEDI-522 in treating patients with unresectable or metastatic kidney cancer. Monoclonal antibodies, such as bevacizumab and MEDI-522, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab and MEDI-522 may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether bevacizumab is more effective when given together with or without MEDI-522 in treating kidney cancer.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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)

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• etaracizumab
Given IV

Biological:
• bevacizumab
Given IV

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Novant Health Presbyterian Medical Center	Charlotte	North Carolina
United States	Fremont - Rideout Cancer Center	Marysville	California
United States	SWOG	Portland	Oregon
United States	University of California at Davis Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose of Bevacizumab , Based on Incidence of Dose-limiting Toxicity (DLT) Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)		Up to 8 weeks	Yes
Primary	Progression-free Survival (Phase II)	Measured from date of registration to date of first observation of progressive disease, symptomatic deterioration or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact.	From date of registration to date of first observation of progressive disease, systemic deterioration, or death due to any cause, assessed up to 3 years	No
Primary	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI CTCAE Version 3.0 (Phase II)	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	Up to 3 years	Yes
Primary	Overall Survival (Phase II)	Measure from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.	From date of registration to date of death due to any cause, assessed up to 3 years	No
Primary	Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST), Including Confirmed and Unconfirmed Complete and Partial Responses (Phase II)	Complete Response (CR) is a complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Partial Response (PR) applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of nonmeasurable disease. No new lesions.	Up to 3 years	No
Secondary	Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug	Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.	Patients were assessed for the first 8 weeks for dose-limiting toxicities, then assessed for adverse events after every cycle (1 cycle = 28 days) of protocol treatment, up to 3 years	Yes