Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors (PTK/RAD)
This study has been completed.
Sponsor:
Daniel George
Collaborator:
Novartis
Information provided by (Responsible Party):
Daniel George, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00303732
First received: March 15, 2006
Last updated: December 13, 2012
Last verified: December 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Kidney Cancer Unspecified Adult Solid Tumor, Protocol Specific |
Drug: RAD001 (everolimus) Drug: PTK787 (vatalanib) |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | PTK787/ZK222584 and RAD001 for Patients With Advanced Solid Tumors |
Resource links provided by NLM:
Further study details as provided by Duke University:
Primary Outcome Measures:
- Maximum tolerated dose (MTD) of vatalanib and everolimus [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: Yes ]Patients were evaluated on Day 1,14 and 28 for dose limiting toxicities
- Safety and tolerability [ Time Frame: Duration of study treatment ] [ Designated as safety issue: Yes ]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) [ Time Frame: Duration of study treatment ] [ Designated as safety issue: Yes ]Patients were assessed for adverse events every 14 days while on study treatment
Secondary Outcome Measures:
- Non dose-limiting toxicity [ Time Frame: Duration of study treatment ] [ Designated as safety issue: Yes ]Patients were assessed every 14 days for non dose-limiting toxicity while on study treatment
- Pharmacokinetics [ Time Frame: Day 14 Cycle 1, Day 1 Cycle 2 ] [ Designated as safety issue: No ]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 [ Time Frame: Day 1 and 28 ] [ Designated as safety issue: No ]Samples were collected on Day 1 and at Day 28 of Cycle 1
- Clinical response in patients with metastatic RCC [ Time Frame: Duration of treatment ] [ Designated as safety issue: No ]patients underwent restaging studies every 2 cycles while on treatment for evidence of disease response
- Overall survival of patients with RCC [ Time Frame: Until death ] [ Designated as safety issue: No ]
- Time to progression of patients with RCC [ Time Frame: Duration of study treatment ] [ Designated as safety issue: No ]Patients were followed for evidence of disease progression as long as they remained on study drug.
| Enrollment: | 32 |
| Study Start Date: | December 2004 |
| Study Completion Date: | August 2012 |
| Primary Completion Date: | August 2010 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: PTK787, RAD001
PTK787 (vatalinib) 1000 mg daily, RAD001 (everolimus) 5 mg daily
|
Drug: RAD001 (everolimus)
Other Name: Afinitor
Drug: PTK787 (vatalanib)
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00303732
Locations
| United States, North Carolina | |
| Duke Comprehensive Cancer Center | |
| Durham, North Carolina, United States, 27710 | |
Sponsors and Collaborators
Daniel George
Novartis
Investigators
| Principal Investigator: | Daniel J. George, MD | Duke Cancer Institute |
More Information
Additional Information:
Publications:
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.
| Responsible Party: | Daniel George, Associate Professor of Medicine, Duke University Medical Center |
| ClinicalTrials.gov Identifier: | NCT00303732 History of Changes |
| Other Study ID Numbers: | Pro00012347, DUMC-6626-04-12R0, CDR0000454988 |
| Study First Received: | March 15, 2006 |
| Last Updated: | December 13, 2012 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Duke University:
|
unspecified adult solid tumor, protocol specific recurrent renal cell cancer stage IV renal cell cancer |
Additional relevant MeSH terms:
|
Carcinoma, Renal Cell Kidney Neoplasms Neoplasms Adenocarcinoma Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Kidney Diseases Urologic Diseases Everolimus Sirolimus |
Vatalanib Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Antibiotics, Antineoplastic Antineoplastic Agents Therapeutic Uses Antifungal Agents Anti-Infective Agents Anti-Bacterial Agents Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 16, 2013