Vatalanib and Everolimus in Treating Patients With Advanced Solid Tumors

NCT00303732 | Completed Phase 1 DMC

• 3 other identifiers: Pro00012347DUMC-6626-04-12R0CDR0000454988
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Kidney Cancer; Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific; recurrent renal cell cancer; stage IV renal cell cancer

Outcome Measures

Primary Outcomes (3)

• Maximum tolerated dose (MTD) of vatalanib and everolimus

  Patients were evaluated on Day 1,14 and 28 for dose limiting toxicities

  Day 1 - 28

• Safety and tolerability

  Adverse events were assessed every 14 days for the length of the treatment period.

  Duration of study treatment

• 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

  Duration of study treatment

Secondary Outcomes (6)

• Non dose-limiting toxicity

  Duration of study treatment

• Pharmacokinetics

  Day 14 Cycle 1, Day 1 Cycle 2

• Changes in the phosphorylation status of S6K protein in peripheral blood mononuclear cells

  Day 1 and 28

• Clinical response in patients with metastatic RCC

  Duration of treatment

• Overall survival of patients with RCC

  Until death

Study Arms (1)

PTK787, RAD001

EXPERIMENTAL

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

Drug: RAD001 (everolimus); Drug: PTK787 (vatalanib)

Interventions

RAD001 (everolimus) DRUG

Also known as: Afinitor

PTK787, RAD001

PTK787 (vatalanib) DRUG

PTK787, RAD001

Eligibility Criteria

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

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Daniel George, MD: lead
• Novartis: collaborator

Study Sites (1)

Duke Comprehensive Cancer Center

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

Everolimus; vatalanib

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Daniel J. George, MD

  Duke Cancer Institute

  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: March 15, 2006
• First Posted: March 17, 2006
• Study Start: December 1, 2004
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2012
• Last Updated: March 3, 2016

Record last verified: 2016-03

Locations

US (1)