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Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors (PTK/RAD)

Primary Purpose

Kidney Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
RAD001 (everolimus)
PTK787 (vatalanib)
Sponsored by
Daniel George, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Kidney Cancer focused on measuring unspecified adult solid tumor, protocol specific, recurrent renal cell cancer, stage IV renal cell cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Duke Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PTK787, RAD001

Arm Description

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

Outcomes

Primary Outcome Measures

Maximum tolerated dose (MTD) of vatalanib and everolimus
Patients were evaluated on Day 1,14 and 28 for dose limiting toxicities
Safety and tolerability
Adverse events were assessed every 14 days for the length of the treatment period.
Safety and tolerability at the MTD in patients with metastatic renal cell carcinoma (RCC)
Patients were assessed for adverse events every 14 days while on study treatment

Secondary Outcome Measures

Non dose-limiting toxicity
Patients were assessed every 14 days for non dose-limiting toxicity while on study treatment
Pharmacokinetics
Blood was drawn for PK assessment on Day 14 of Cycle 1 and Day 1 of Cycle 2
Changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells
Samples were collected on Day 1 and at Day 28 of Cycle 1
Clinical response in patients with metastatic RCC
patients underwent restaging studies every 2 cycles while on treatment for evidence of disease response
Overall survival of patients with RCC
Time to progression of patients with RCC
Patients were followed for evidence of disease progression as long as they remained on study drug.

Full Information

First Posted
March 15, 2006
Last Updated
March 1, 2016
Sponsor
Daniel George, MD
Collaborators
Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT00303732
Brief Title
Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors
Acronym
PTK/RAD
Official Title
PTK787/ZK222584 and RAD001 for Patients With Advanced Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
December 2004 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Daniel George, MD
Collaborators
Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Kidney Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Keywords
unspecified adult solid tumor, protocol specific, recurrent renal cell cancer, stage IV renal cell cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
37 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PTK787, RAD001
Arm Type
Experimental
Arm Description
PTK787 (vatalinib) 1000 mg daily, RAD001 (everolimus) 5 mg daily
Intervention Type
Drug
Intervention Name(s)
RAD001 (everolimus)
Other Intervention Name(s)
Afinitor
Intervention Type
Drug
Intervention Name(s)
PTK787 (vatalanib)
Primary Outcome Measure Information:
Title
Maximum tolerated dose (MTD) of vatalanib and everolimus
Description
Patients were evaluated on Day 1,14 and 28 for dose limiting toxicities
Time Frame
Day 1 - 28
Title
Safety and tolerability
Description
Adverse events were assessed every 14 days for the length of the treatment period.
Time Frame
Duration of study treatment
Title
Safety and tolerability at the MTD in patients with metastatic renal cell carcinoma (RCC)
Description
Patients were assessed for adverse events every 14 days while on study treatment
Time Frame
Duration of study treatment
Secondary Outcome Measure Information:
Title
Non dose-limiting toxicity
Description
Patients were assessed every 14 days for non dose-limiting toxicity while on study treatment
Time Frame
Duration of study treatment
Title
Pharmacokinetics
Description
Blood was drawn for PK assessment on Day 14 of Cycle 1 and Day 1 of Cycle 2
Time Frame
Day 14 Cycle 1, Day 1 Cycle 2
Title
Changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells
Description
Samples were collected on Day 1 and at Day 28 of Cycle 1
Time Frame
Day 1 and 28
Title
Clinical response in patients with metastatic RCC
Description
patients underwent restaging studies every 2 cycles while on treatment for evidence of disease response
Time Frame
Duration of treatment
Title
Overall survival of patients with RCC
Time Frame
Until death
Title
Time to progression of patients with RCC
Description
Patients were followed for evidence of disease progression as long as they remained on study drug.
Time Frame
Duration of study treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel J. George, MD
Organizational Affiliation
Duke Cancer Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke Comprehensive Cancer Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Citations:
Citation
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.
Results Reference
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Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors

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