Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors

NCT ID: NCT00303732

Last Updated: 2016-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2012-08-31

Brief Summary

RATIONALE: Vatalanib and everolimus may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase I trial is studying the side effects and best dose of vatalanib and everolimus and to see how well they work in treating patients with advanced solid tumors.

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose (MTD) of vatalanib and everolimus in patients with advanced solid tumors.
• Determine the safety and tolerability of vatalanib and everolimus in patients with advanced solid tumors.
• Evaluate the safety and tolerability of vatalanib and everolimus at the MTD in patients with metastatic renal cell carcinoma (RCC).

Secondary

• Describe the non dose-limiting toxic effects associated with vatalanib and everolimus.
• Describe the pharmacokinetics of vatalanib and everolimus in patients with advanced solid tumors.
• Determine the functional extent of mTOR inhibition by changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells in patients treated with vatalanib and everolimus.
• Describe any clinical responses seen in patients with metastatic RCC in a dose-expansion cohort treated at the MTD.
• Observe overall survival of RCC patients treated with vatalanib and everolimus.
• Determine the time to progression of patients with RCC treated with vatalanib and everolimus.

OUTLINE: This is a phase I dose-escalation study followed by a phase Ib study.

• Phase I (solid tumors): Patients receive oral vatalanib on days 1-28 and oral everolimus on days 15-28 during course 1 and on days 1-28 during all subsequent courses. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of vatalanib and everolimus 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 Ib (renal cell carcinoma only): Patients receive oral vatalanib and oral everolimus at the MTD on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.

Conditions

Kidney Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

PTK787, RAD001

PTK787 (vatalinib) 1000 mg daily, RAD001 (everolimus) 5 mg daily

Group Type: EXPERIMENTAL

RAD001 (everolimus)

Intervention Type: DRUG

PTK787 (vatalanib)

Intervention Type: DRUG

Interventions

RAD001 (everolimus)

Intervention Type: DRUG

PTK787 (vatalanib)

Intervention Type: DRUG

Other Intervention Names

Afinitor

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor with radiographic evidence of metastatic disease

• No standard therapy exists (phase I)
• Unresectable or metastatic renal cell carcinoma (phase Ib)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 9 g/dL
• AST or ALT ≤ 2.5 times upper limit of normal (ULN)
• Total cholesterol < 300 mg/dL
• Triglycerides < 350 mg/dL
• Bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN OR creatinine clearance > 40 mL/min
• Negative proteinuria by dip stick OR total urinary protein ≤ 500 mg
• No uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with antihypertensive regimen
• No unstable angina pectoris
• No symptomatic congestive heart failure (New York Heart Association class III or IV heart disease)
• No uncontrolled serious cardiac arrhythmia (symptomatic supraventricular tachycardia or any ventricular tachycardia/fibrillation)
• No myocardial infarction in the past 6 months
• No uncontrolled diabetes
• No interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
• No active or uncontrolled infection
• No uncontrolled hyperlipidemia
• No chronic renal disease
• No acute or chronic liver disease (e.g., hepatitis or cirrhosis)
• No impaired gastrointestinal (GI) function OR GI disease that may significantly alter the absorption of vatalanib or everolimus, including any of the following:

• Ulcerative disease
• Uncontrolled nausea and vomiting with solid food
• Watery diarrhea > 5 times daily
• Malabsorption syndrome
• Bowel obstruction
• Inability to swallow the tablets
• No confirmed HIV infection
• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other concurrent severe and/or uncontrolled medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY:

• Recovered from prior therapy
• No prior antivascular endothelial growth factor therapy
• More than 4 weeks since prior major surgery* (laparotomy)
• More than 2 weeks since prior minor surgery*
• More than 4 weeks since prior chemotherapy (6 weeks for mitomycin C or nitrosoureas)
• More than 6 weeks since prior antibody therapy
• More than 2 weeks since prior biologic/immunotherapy
• More than 2 weeks since prior limited-field radiotherapy
• More than 4 weeks since prior full-field radiotherapy
• More than 4 weeks since prior investigational agents
• Prior transfusions allowed provided blood counts are stable for > 2 weeks
• Concurrent epoetin alfa allowed
• No concurrent warfarin or similar oral anticoagulants that are metabolized by the cytochrome P450 system

• Heparin and low molecular weight heparin allowed NOTE: *Insertion of a vascular access device is not considered major or minor surgery

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

Daniel George, MD

OTHER

Sponsor Role: lead

Responsible Party

Daniel George, MD

Associate Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel J. George, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Cancer Institute

Locations

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Countries

United States

References

Speca JC, Mears AL, Creel PA, et al.: Phase I study of PTK787/ZK222584 (PTK/ZK) and RAD001 for patients with advanced solid tumors and dose expansion in renal cell carcinoma patients. [Abstract] J Clin Oncol 25 (Suppl 18): A-5039, 244s, 2007.

Reference Type: RESULT

Other Identifiers

DUMC-6626-04-12R0

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000454988

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00012347

Identifier Type: -

Identifier Source: org_study_id