Erlotinib and Sirolimus for the Treatment of Metastatic Renal Cell Carcinoma

NCT00353301 | Completed Phase 2 Results DMC

• 1 other identifier: 05-1135.cc
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and efficacy of the combination of erlotinib hydrochloride (Tarceva™) and sirolimus (Rapamune™) in the treatment of patients with metastatic kidney cancer.

Conditions

Renal Cell Carcinoma

Keywords

Carcinoma, Renal Cell; Receptor, Epidermal Growth Factor; mTOR protein; Sirolimus; Erlotinib

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Time to progression was defined as the time from beginning of therapy until disease progression or death. For subjects who had not progressed at the time of statistical analysis, progression-free survival was censored at the date of their last tumor assessment. Kaplan-Meier method was used to estimate median progression-free survival. Progression was defined as radiographic progression according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (year 2000 version), non-compliance in obtaining scans, unequivocal clinical progression or the initiation of another medication for the treatment of renal cell carcinoma.

  Physical exam assessments were performed every 4 weeks during the treatment phase. Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.

Secondary Outcomes (1)

• Overall Survival

  Survival follow-up information was collected every 4 months following the termination visit until death, loss to follow-up, or study termination up to 275 weeks.

Study Arms (1)

Erlotinib and Sirolimus

EXPERIMENTAL

Erlotinib hydrochloride (Tarceva) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. During the treatment period, patients will receive single-agent Tarceva, 150 mg/day. Sirolimus (Rapamune) will be self-administered in an open-label unblinded manner to all patients enrolled in the study. Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Drug: Erlotinib hydrochloride; Drug: Sirolimus

Interventions

Erlotinib hydrochloride DRUG

Patients will receive single-agent Tarceva, 150 mg/day

Also known as: Tarceva

Erlotinib and Sirolimus

Sirolimus DRUG

Patients will receive a loading dose of 6 mg of Rapamune seven days after beginning treatment with Tarceva™ followed by a dose of 2mg/day.

Also known as: Rapamune

Erlotinib and Sirolimus

Eligibility Criteria

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

You may qualify if:

• Signed informed consent to participate in this study.
• Histological diagnosis of renal cell carcinoma.
• Age greater or equal 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance status of 2 or better.
• Life expectancy of at least 3 months.
• Failure or intolerance to previous treatment with Sutent® and/or Nexavar®.
• Most recent systemic treatment at least 1 month from the beginning of treatment.
• Most recent local treatment (surgery or irradiation) \> 2 weeks from the beginning of treatment.
• At least one site of measurable disease by CT scan or MRI (RECIST criteria).
• Baseline hemoglobin \>9 g/dl, platelets \> 100,000/mm3, absolute neutrophil count (ANC \>1500/mm3.

You may not qualify if:

• Previous treatment with Tarceva™, Iressa™, Rapamune™, temsirolimus or everolimus.
• Untreated metastasis to the central nervous system.
• Previous solid organ, bone marrow or stem-cell transplant.
• Known AIDS or HIV infection.
• Symptomatic or poorly controlled chronic heart failure.
• Chronic renal failure requiring dialysis on a regular basis.
• Chronic liver failure.
• Serum aspartate aminotransferase (AST), Alanine Aminotransferase (ALT), alkaline phosphatase or bilirubin \>1.5 x the upper limit of normal for the local laboratory.
• Pregnant or breast-feeding women.
• Other invasive malignant diseases within 5 years (other than squamous or basal cell carcinoma of the skin).
• Inability to provide informed consent
• Any other serious and/or unstable medical, psychiatric, or other condition considered by the P.I. to preclude safe or reasonably compliant participation in the protocol.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Colorado Hospital

Aurora, Colorado, 80010, United States

Location

Related Publications (1)

• Gemmill RM, Zhou M, Costa L, Korch C, Bukowski RM, Drabkin HA. Synergistic growth inhibition by Iressa and Rapamycin is modulated by VHL mutations in renal cell carcinoma. Br J Cancer. 2005 Jun 20;92(12):2266-77. doi: 10.1038/sj.bjc.6602646.

  PMID: 15956968 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Erlotinib Hydrochloride; Sirolimus

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)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

One limitation of this study was the lack of von Hippel-Lindau (VHL) mutational status assessment.

Results Point of Contact

• Title: Dr. Thomas Flaig
• Organization: University of Colorado, Denver

Thomas.Flaig@ucdenver.edu

(720) 848-0655

Study Officials

• Thomas W Flaig, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2006
• First Posted: July 18, 2006
• Study Start: July 1, 2006
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: April 14, 2014
• Results First Posted: February 17, 2014

Record last verified: 2014-03

Locations

US (1)