Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Recurrence

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

All Drugs and Chemicals

Antineoplastic Agents

Herbal and Botanical

Antibodies

Antibodies, Monoclonal

Irinotecan

Immunoglobulins

Cola

etaracizumab

Leonard B. Saltz, MD

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer that has not responded to irinotecan.

OBJECTIVES:

* Determine the recommended phase II dose of monoclonal antibody anti-anb3 integrin in patients with irinotecan-refractory advanced colorectal cancer.
* Determine the safety and tolerance of this drug in these patients.
* Determine any antitumor activity of this drug in these patients.
* Determine the objective response rate, response duration, and time to progression in patients treated with this drug.
* Determine the pharmacokinetics of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive monoclonal antibody anti-anb3 integrin IV over 30 minutes once weekly on weeks 1-52 in the absence of disease progression or unacceptable toxicity. Patients with responding disease may continue therapy.

Cohort of 4-6 patients receive escalating doses of monoclonal antibody anti-anb3 integrin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 4 or 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose in the phase II portion of the study.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 4-24 patients will be accrued for phase I of this study and a total of 40 patients will be accrued for phase II of this study.

Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer

Phase I/II Study of MEDI-522, A Humanized Monoclonal Antibody Directed Against the Human Alpha V Beta 3 Integrin, in Patients With Irinotecan-Refractory Advanced Colorectal Cancer

National Cancer Institute (NCI)

Memorial Sloan Kettering Cancer Center

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Carcinoma, Renal Cell

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Bevacizumab

Antibodies, Anti-Idiotypic

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

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

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

bevacizumab

Christopher Ryan

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.

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.

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

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)

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.

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.

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.

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.

Patients receive bevacizumab (10/mg/kg or 5 mg/kg) 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 I Bevacizumab (10 mg/kg) + MEDI-522

Patients receive bevacizumab (10 mg/kg or 5mg/kg) 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.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Study Statistician

Patients receive bevacizumab (10 mg/kg or 5 mg/kg) 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.

The study was permanently closed to accrual on April 1, 2009, due to drug supply issues.

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)

Phase II Arm I

Phase II Arm II

Progression-free Survival (Phase II)

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)

Overall Survival (Phase II)

Response Rate According to Response Evaluation Criteria in Solid Tumors (RECIST), Including Confirmed and Unconfirmed Complete and Partial Responses (Phase II)

Allergic reaction/hypersensitivity

Dyspnea (shortness of breath)

Patients receive bevacizumab (10/mg/kg or 5 mg/kg) 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 un til the recommended phase II dose (RPTD) of bevacizumab is determined.

Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.

Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer	NCT00027729	Colorectal Canc...	etaracizumab	18 Years -	Memorial Sloan Kettering Cancer Center
Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer	NCT00027729	Colorectal Canc...	etaracizumab	18 Years -	Memorial Sloan Kettering Cancer Center
Bevacizumab With or Without MEDI-522 in Treating Patients With Unresectable or Metastatic Kidney Cancer	NCT00684996	Recurrent Renal... Renal Cell Carc... Stage III Renal... Stage IV Renal ...	etaracizumab bevacizumab	-	National Cancer Institute (NCI)
Monoclonal Antibody Therapy in Treating Patients With Advanced Colorectal Cancer	NCT00027729	Colorectal Canc...	etaracizumab	18 Years -	Memorial Sloan Kettering Cancer Center

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