CCI-779 and Bevacizumab in Treating Patients With Metastatic or Unresectable Kidney Cancer

NCT00112840 | Completed Phase 1 Results

• 6 other identifiers: NCI-2009-00109CDR0000428311NCI-6986MC04526986N01CM62205
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

This phase I/II trial is studying the side effects and best dose of CCI-779 and bevacizumab and to see how well they work in treating patients with metastatic or unresectable kidney cancer. Drugs used in chemotherapy, such as CCI-779, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving CCI-779 together with bevacizumab may kill more tumor cells.

Conditions

Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicity (DLT) (Phase I)

  For this protocol, dose limiting toxicity (DLT) will be defined as an adverse event attributed (definitely, probably, or possibly) to the study treatment in the first four weeks of combination therapy, and meeting the following criteria: * Grade 4 Absolute neutrophil count (ANC) for 5+ days. * Grade 4 anemia or thrombocytopenia of any duration. * Serum Creatinine 2 times baseline or 2x upper limit of normal if baseline levels not normal. * Any other non-hematologic grade 3 or higher as per NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0, except fatigue and grade 3 Hypertension that is will be controlled with oral medication. * Grade 3 triglycerides will be a DLT for patients who have Grade 3 in spite of appropriate lipid lowering drug therapy. The maximum tolerated dose level (MTD) will be defined as the highest safely tolerated dose where 1 or 0 out of 6 patients experience DLT with the next higher dose.

  Patients observed a minimum of 4 weeks (one full course). The maximum number of cycles observed was 16 cycles.

• Proportion of Progression-free Patients at 6 Months (Phase II)

  Determination of progression will be made according to Response Evaluation Criteria in Solid Tumors (RECIST). A progression (PD) is defined as having at least a 20% increase in the sum of the longest dimension of target lesions taking as reference the smallest sum of the largest dimension recorded at baseline.The proportion of progression-free patients will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the success proportion will be calculated. All patients meeting the eligibility criteria who have signed a consent form and begun treatment will be considered evaluable. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred.

  6 months after study entry

Secondary Outcomes (3)

• Clinical Best Response Rate of CCI-779 and Bevacizumab in Patients With Metastatic Renal Cell (Phase II)

  Up to 3 years from study registration

• Time to Progression (Phase II)

  Up to 3 years from study registration

• Overall Survival (Phase I and II)

  Up to 3 years from study registration

Study Arms (1)

CCI-779 and bevacizumab

EXPERIMENTAL

Patients receive CCI-779 IV on days 1, 8, 15, and 22 and bevacizumab IV on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of CCI-779 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 CCI-779 and bevacizumab as in phase I at the MTD determined in phase I. After completion of study treatment, patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after study entry.

Drug: CCI-779; Drug: Bevacizumab

Interventions

CCI-779 DRUG

CCI-779 is taken IV on days 1, 8, 15, 22 of a 28-day cycle. Dose level is dependent on phase.

Also known as: Temsirolimus, Torisel Rapamycin analog, WAY-130779

CCI-779 and bevacizumab

Bevacizumab DRUG

Bevacizumab is taken IV on Days 1 and 15 of a 28-day cycle. Dose Level determined by phase.

CCI-779 and 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 metastatic or unresectable renal cell cancer
• Must have a component of conventional clear cell histology
• The following histologies are excluded:
• True papillary
• Sarcomatoid features without any clear cell component
• Chromophobe
• Oncocytoma
• Collecting duct tumors
• Transitional cell carcinoma
• Measurable disease, defined as ≥ 1 lesion ≥ 2.0 cm in the longest diameter by conventional techniques OR ≥ 1.0 cm by spiral CT scan
• Tumor tissue (from primary tumor or metastases) available AND patient is willing to donate blood for research studies (phase II only)
• No CNS metastases by head CT scan or MRI
• Performance status - ECOG 0-2
• Absolute neutrophil count ≥ 1,500/mm\^3
• Platelet count ≥ 100,000/mm\^3

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

temsirolimus; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney 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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jaime Merchan, M.D.
• Organization: University of Miami - Sylvester Comprehensive Cancer Center

jmerchan2@med.miami.edu

Study Officials

• Jaime Merchan

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2005
• First Posted: June 3, 2005
• Study Start: May 1, 2005
• Primary Completion: August 9, 2010
• Study Completion: September 10, 2015
• Last Updated: February 1, 2022
• Results First Posted: September 11, 2014

Record last verified: 2022-01

Locations

US (2)