Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

NCT00655655 | Completed Phase 1

• 2 other identifiers: MC0414NCI-2009-01200
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Everolimus and vatalanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with vatalanib may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of everolimus and vatalanib in treating patients with advanced solid tumors.

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Metastatic Gastrointestinal Carcinoid Tumor; Metastatic Pheochromocytoma; Pancreatic Polypeptide Tumor; Recurrent Gastrointestinal Carcinoid Tumor; Recurrent Islet Cell Carcinoma; Recurrent Melanoma; Recurrent Neuroendocrine Carcinoma of the Skin; Recurrent Non-small Cell Lung Cancer; Recurrent Pheochromocytoma; Recurrent Renal Cell Cancer; Somatostatinoma; Stage III Neuroendocrine Carcinoma of the Skin; Stage IV Melanoma; Stage IV Non-small Cell Lung Cancer; Stage IV Renal Cell Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (7)

• Maximum tolerated dose of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)

  Up to 28 days post treatment cycle

• Toxicity associated with everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)

  Up to 28 days post treatment cycle

• Therapeutic antitumor activity of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)

  Up to 28 days post treatment cycle

• Recommended phase II dose (RP2D) of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06)

  After MTD (maximum tolerate dose) is determined from Phase I

• Biological activity and therapeutic antitumor activity of everolimus and vatalanib when given at the MTD/RPTD (Cohort II)

  Post treatment cycle

• Evaluation of pharmacogenetic, metabolic, and clinical markers that may predict hypertension induced by anti-VEGF therapy (Cohort II)

  Day 1 and 14 of Cycle 1 of treatment

• Efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine carcinoma, non-small cell lung cancer, or melanoma (Cohort II)

  Post treatment cycle with MTD outcomes

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

Drug: everolimus; Drug: vatalanib; Other: pharmacological study; Other: laboratory biomarker analysis; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Procedure: ultrasound imaging

Interventions

everolimus DRUG

Given orally

Also known as: 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001

Arm I

vatalanib DRUG

Given orally

Also known as: CGP-79787, PTK787/ZK 222584

Arm I

pharmacological study OTHER

Correlative study (Cohort IIA only)

Also known as: pharmacological studies

Arm I

laboratory biomarker analysis OTHER

Correlative study (Cohorts IIA and IIB)

Arm I

dynamic contrast-enhanced magnetic resonance imaging PROCEDURE

Correlative study (Cohort IIA only)

Also known as: DCE-MRI

Arm I

ultrasound imaging PROCEDURE

Correlative study (Cohorts IIA and IIB)

Also known as: ultrasonography, ultrasound, ultrasound test

Arm I

Eligibility Criteria

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

You may qualify if:

• Histologic proof of cancer that is now unresectable (solid tumors, excluding lymphoma)
• Ability to provide informed consent
• Willingness to return to Mayo Clinic Rochester for follow up
• Life expectancy \>= 12 weeks
• Prior anti-VEGF therapy allowed
• Cohort IIA: Patients meeting other eligibility criteria, regardless of histopathologic diagnosis; tumor that is amenable to biopsy; willingness to provide blood specimens, undergo DCE-MRI, and undergo brachial artery ultrasound measurements as required by the protocol
• The following laboratory values obtained =\< 14 days prior to registration:
• Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary protein =\< 500 mg and measured creatinine clearance (CrCl) \>= 50 mL/min from a 24-hour urine collection
• Cohort IIB: Patients meeting other eligibility criteria AND with pathologic diagnosis of metastatic kidney cancer, neuroendocrine carcinoma, melanoma, and NSCLC; willingness to provide blood specimens required and undergo brachial artery ultrasound measurements
• The following laboratory values obtained =\< 14 days prior to registration:
• ANC \>= 1500/uL; Hgb \>= 9 g/dL; PLT \>= 100,000/uL; Total bilirubin =\< 1.5 x upper limit of normal (ULN); AST =\< 3 x ULN or AST =\< 5 x ULN if liver involvement; Creatinine =\< 1.5 x ULN; INR =\< 1.4 (Cohort IIA only)

You may not qualify if:

• Any of the following prior therapies: Full field radiation therapy =\<4 weeks prior to registration or limited field radiation therapy =\< 2 weeks prior to registration; Radiation to \>30% of bone marrow; Major surgery (i.e., laparotomy) =\< 4 weeks prior to registration; Minor surgery =\< 2 weeks prior to registration
• New York Heart Association classification III or IV
• Uncontrolled hypertension, labile hypertension or history of poor compliance with antihypertensive medication
• Active, bleeding diathesis or on any anticoagulant except patients receiving heparin for deep venous thrombosis prophylaxis (not treatment)
• CNS metastases or seizure disorder
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation
• Any concurrent severe and/or uncontrolled medical conditions which could compromise participation or pose as unnecessary risk to the patient in the study, including, but not limited, to the following: Unstable angina; Myocardial infarction =\< 6 months prior to registration; Serious uncontrolled cardiac arrhythmia; Uncontrolled diabetes
• Any concurrent severe and/or uncontrolled medical conditions which could compromise participation or pose as unnecessary risk to the patient in the study, including, but not limited, to the following: Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung; QTc \> 500 msec; Patients who require chronic treatment with PPI or H2 antagonist
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets)
• Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
• Chemotherapy =\< 3 weeks; Mitomycin C/nitrosoureas =\< 6 weeks; Immunotherapy =\< 2 weeks; Biologic therapy =\< 2 weeks; Prior investigational therapy =\< 4 weeks; Full field radiation therapy =\< 4 weeks or limited field radiation therapy =\< 2 weeks; Radiation to \> 30% of bone marrow; Major surgery (i.e., laparotomy) =\< 4 weeks; or Minor surgery =\< 2 weeks prior to registration
• Any of the following: pregnant women; nursing women; men or women of childbearing potential who are unwilling to employ adequate barrier contraception
• Patients on whom DCE-MRI is contraindicated (e.g., presence of MRI-incompatible metallic implants or prosthetic heart valves, pacemakers, etc.) are ineligible
• ECOG performance status (PS) 3 or 4
• Treatment with medications listed in Appendix I for which no safer or more efficacious alternative is available

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Gastrinoma; Glucagonoma; Insulinoma; Pheochromocytoma; Carcinoma, Islet Cell; Melanoma; Carcinoma, Merkel Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell; Somatostatinoma; Carcinoma, Medullary

Interventions

Everolimus; vatalanib; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Adenoma, Islet Cell; Adenoma; Paraganglioma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Julian R. Molina, M.D., Ph.D.

  Mayo Clinic

  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

Study Record Dates

• First Submitted: April 9, 2008
• First Posted: April 10, 2008
• Study Start: December 1, 2004
• Primary Completion: September 15, 2009
• Study Completion: January 11, 2018
• Last Updated: August 21, 2024

Record last verified: 2024-08

Locations

US (1)