A Phase I Study of Bevacizumab and Sunitinib in Metastatic Renal Cell Carcinoma Patients

NCT00421512 | Completed Phase 1

• 1 other identifier: 06-016
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety of bevacizumab and sunitinib given in combination for kidney cancer. The drugs act to stop blood vessel growth but in different ways. They have not been studied together in a previous study. We also want to find out what effects (good and bad) the combination of bevacizumab and sunitinib have on you and your tumor.

Conditions

Metastatic Renal Cell Carcinoma; Kidney Cancer

Keywords

Renal cell carcinoma; Metastatic; Kidney Cancer; Bevacizumab; Sunitinib

Outcome Measures

Primary Outcomes (1)

• To assess the maximum tolerated dose and overall safety and tolerability of sunitinib administered in combination with bevacizumab for the treatment of patients with metastatic renal cell carcinoma.

  DLT determination will be based on toxicities observed in Cycles 1

Secondary Outcomes (2)

• To assess antitumor activity of the combination of sunitinib and bevacizumab.

  28 days +/- 3

• To evaluate serum levels of vascular endothelial growth factor (VEGF)

  every 28 days of a cycle +/- 3 days

Interventions

Bevacizumab and Sunitinib DRUG

On Cycle 1, Day 0, patients will begin treatment with bevacizumab. Sunitinib will begin on Day 1. The starting dose for sunitinib will be 25mg orally daily. sunitinib will be given in a four weeks on-two weeks off schedule. Bevacizumab will begin on Day 0 and will be administered every two weeks at 10mg/kg. A cycle of therapy is 6 weeks. The sunitinib dose escalation portion of the trial will be performed to determine the MTD of sunitinib given in combination with bevacizumab. Once the MTD has been determined, 10 additional patients will be treated at the MTD of sunitinib in combination with bevacizumab.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed renal cell carcinoma (of any histological subtype) and with metastases. Patients with unresected primary tumors may be enrolled as long as evidence of metastatic disease is also present.
• Evidence of unidimensionally measurable disease (i.e., greater than or equal to 1 malignant tumor mass that can be accurately measured in at least 1 dimension greater than or equal to 20 mm with conventional computerized tomography \[CT\] or magnetic resonance imaging \[MRI\], or greater than or equal to 10 mm with spiral CT scan \[if spiral CT scan is used, minimum lesion size should be twice the reconstruction interval used, e.g., if reconstruction size is 7 mm, lesion size should be greater than or equal to 14 mm\]).
• Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable.
• Male or female, 18 years of age or older.
• ECOG performance status 0 or 1.
• Resolution of all acute toxic effects of prior chemotherapy, radiotherapy, or surgical procedure to NCI CTCAE grade less than or equal to 1.
• Adequate organ function as defined by the following criteria:
• Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase \[SGOT\]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase \[SGPT\]) less than or equal to 1.5 x upper limit of normal (ULN)
• Total serum bilirubin less than or equal to 1.5 mg/dL
• Total white blood cell count greater than or equal to 3000 cells/µL
• Absolute neutrophil count (ANC) greater than or equal to 1500/µL
• Platelets greater than or equal to 100,000/µL
• Hemoglobin greater than or equal to 9.0 g/dL
• Serum calcium less than or equal to 12.0 mg/dL
• Serum creatinine less than or equal to 2.0 x ULN

You may not qualify if:

• Patients eligible for the higher priority IRB protocol #07-066
• Major surgery, open biopsy, traumatic injury, radiation or systemic therapy within 4 weeks of starting the study treatment. Anticipation of major surgical procedure during the study. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
• More than 2 prior systemic therapies for metastatic RCC.
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0.
• NCI CTCAE grade 3 hemorrhage within the past 1 month.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.
• History of or known brain metastases, current spinal cord compression, or carcinomatous meningitis.
• Any of the following within the 12 months prior to study drug administration:
• severe/unstable angina, MI, CABG, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack or peripheral vascular disease.
• Ongoing cardiac dysrhythmias of NCI CTCAE grade greater than or equal to 2, atrial fibrillation of any grade, or prolongation of the QTc interval to \>450 msec for males and \>470 msec for females.
• Blood pressure \> 150/90mmHg
• Evidence of bleeding diathesis or coagulopathy
• Serious, non-healing wound, ulcer or bone fracture
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
• Current treatment on another therapeutic clinical trial.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan-Kettering Cancer Center 1275 York Avenue

New York, New York, 10021, United States

Location

Related Links

• Memorial Sloan-Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Neoplasm Metastasis

Interventions

Bevacizumab; Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Robert Motzer, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 10, 2007
• First Posted: January 12, 2007
• Study Start: March 1, 2006
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: November 11, 2008

Record last verified: 2008-11

Locations

US (1)