A Phase Ib Study of Rad001 and Sutent to Treat Renal Cell Carcinoma

NCT00788060 | Completed Phase 1

• 1 other identifier: Pro00000548
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, Phase Ib study of Sunitinib and RAD001 in patients with advanced RCC. The study design is a phase I interpatient dose-escalation with a dose expansion at the maximum tolerated dose (MTD) in patients with metastatic RCC . In the dose escalation portion, patients will be treated with sunitinib, given in an intermittent schedule (2 weeks of daily dosing followed by one week off drug. RAD001 will be given daily. Escalation of both drugs will occur as tolerated. Treatment will be arbitrarily divided into 3-week cycles, with dose limiting toxicity (DLT) determined by Cycle 2 Day 0.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma; Rad001; Sutent

Outcome Measures

Primary Outcomes (3)

• To determine the maximum tolerated dose (MTD)/recommended Phase 2 regimen of 2+1 dosing with Sunitinib and daily RAD001 in patients with advanced renal cell carcinoma.

  1 year

• To determine the safety and tolerability of 2+1 dosing of Sunitinib and daily RAD001 in patients with advanced RCC

  1 year

• To more fully evaluate the safety and tolerability of 2+1 dosing of Sunitinib and daily RAD001 at the MTD/recommended Phase 2 dose in patients with advanced RCC

  1 year

Secondary Outcomes (5)

• Describe the non-dose limiting toxicities associated with combination therapy using 2+1 dosing Sunitinib and daily RAD001.

  1 year

• Describe the pharmacokinetics of Sunitinib and RAD001 and evaluate any association with disease response

  1 year

• To estimate objective response rate (partial or complete) seen in patients with advanced RCC in a dose expansion cohort treated at the MTD or recommended Phase 2 dose regimen

  1 year

• To estimate the overall survival of RCC patients treated with Sunitinib and RAD001

  1 year

• To estimate the time to disease progression of RCC patients treated with Sunitinib and RAD001

  1 year

Study Arms (1)

RAD001

EXPERIMENTAL

Drug: Everolimus (RAD001); Drug: Sunitinib (Sutent)

Interventions

Everolimus (RAD001) DRUG

5mg per day, continuously

Also known as: RAD001

RAD001

Sunitinib (Sutent) DRUG

37.5 mg per day, 14 days on, 7 day break

Also known as: Sutent

RAD001

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed diagnosis of RCC.
• Patients must have undergone a nephrectomy
• Clinical or radiographic evidence of metastatic disease.
• A minimum of 4 weeks from full field radiation therapy, surgery, chemotherapy or other investigational agent. Treatment may begin one week following limited field radiation therapy.
• Subjects who have received prior limited field radiotherapy, biologic/immunotherapy or surgery must have a documented recovery period \> 2 weeks
• Patients must have normal organ and marrow function as defined below:
• hemoglobin \> 9.0g/dL absolute neutrophil count \> 1,500/μl platelets \> 100,000/μl total bilirubin \< 1.5 X upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) \< 2.5 X ULN creatinine \< 1.5 X ULN (or 24 hour measured creatinine clearance \> 40 mL/min) total fasting cholesterol \< 350 total triglycerides \< 300
• Age \> 18 years.
• ECOG score of 0-2 (See Appendix 11.1).
• For patients with diabetes a Hgb A1C of ≤ 8
• Subject agrees to use a medically acceptable form of birth control during and for at least 3 months after completion of the study treatment, if he/she is sexually active
• Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to treatment
• Ability to swallow and retain oral medication.
• Ability to understand and the willingness to sign a written informed consent document.
• Written informed consent obtained according to local guidelines

You may not qualify if:

• History of solid organ or stem cell transplantation. Also, no current use of chronic immunosuppressive therapy is allowed.
• Patients with active brain metastases (or history of brain metastases) should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• History of HIV, hepatitis B, or hepatitis C infection.
• Patients who have received investigational, biologic, hormonal (other than ADT), immunotherapy, or chemotherapy less than 4 weeks prior to entry on this study or have not recovered from the toxic effects of such therapy.
• Patients who have experienced severe trauma or undergone major surgery within 4 weeks prior to entry on this study or have not recovered to grade 1 or less may not participate.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (requiring antifungal, antibiotic or antiviral therapy), symptomatic congestive heart failure (NYHC II or greater), unstable angina pectoris, cardiac arrhythmia (uncontrolled SVT or any VT), uncontrolled diabetes or psychiatric illness/social situations that would limit compliance with study requirements.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection).
• Patients who have received prior treatment with an mTOR inhibitor.
• Patients who have received prior treatment with Sunitinib are not eligible to participate in this study.

Sponsors & Collaborators

• Daniel George, MD: lead
• Novartis: collaborator
• Pfizer: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Everolimus; Sunitinib

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)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Daniel J. George, M.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 6, 2008
• First Posted: November 10, 2008
• Study Start: October 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 16, 2015

Record last verified: 2015-02

Locations

US (1)