Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

Phase 1

Completed

• 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

• Registration Number: NCT00655655
• Lead Sponsor: Mayo Clinic

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-4-9
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

Inclusion Criteria:<br><br> - Histologic proof of cancer that is now unresectable (solid tumors, excluding<br> lymphoma)<br><br> - Ability to provide informed consent<br><br> - Willingness to return to Mayo Clinic Rochester for follow up<br><br> - Life expectancy >= 12 weeks<br><br> - Prior anti-VEGF therapy allowed<br><br> - Cohort IIA: Patients meeting other eligibility criteria, regardless of<br> histopathologic diagnosis; tumor that is amenable to biopsy; willingness to provide<br> blood specimens, undergo DCE-MRI, and undergo brachial artery ultrasound<br> measurements as required by the protocol<br><br> - The following laboratory values obtained =< 14 days prior to registration:<br><br>Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for<br>protein on dip stick reading, then total urinary protein =< 500 mg and measured<br>creatinine clearance (CrCl) >= 50 mL/min from a 24-hour urine collection<br><br> - Cohort IIB: Patients meeting other eligibility criteria AND with pathologic<br> diagnosis of metastatic kidney cancer, neuroendocrine carcinoma, melanoma, and<br> NSCLC; willingness to provide blood specimens required and undergo brachial artery<br> ultrasound measurements<br><br> - The following laboratory values obtained =< 14 days prior to registration:<br><br>ANC >= 1500/uL; Hgb >= 9 g/dL; PLT >= 100,000/uL; Total bilirubin =< 1.5 x upper limit of<br>normal (ULN); AST =< 3 x ULN or AST =< 5 x ULN if liver involvement; Creatinine =< 1.5 x<br>ULN; INR =< 1.4 (Cohort IIA only)<br><br>Exclusion Criteria:<br><br> - Any of the following prior therapies: Full field radiation therapy =<4 weeks prior<br> to registration or limited field radiation therapy =< 2 weeks prior to registration;<br> Radiation to >30% of bone marrow; Major surgery (i.e., laparotomy) =< 4 weeks prior<br> to registration; Minor surgery =< 2 weeks prior to registration<br><br> - New York Heart Association classification III or IV<br><br> - Uncontrolled hypertension, labile hypertension or history of poor compliance with<br> antihypertensive medication<br><br> - Active, bleeding diathesis or on any anticoagulant except patients receiving heparin<br> for deep venous thrombosis prophylaxis (not treatment)<br><br> - CNS metastases or seizure disorder<br><br> - Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy<br> considered investigational (utilized for a non-FDA-approved indication and in the<br> context of a research investigation<br><br> - Any concurrent severe and/or uncontrolled medical conditions which could compromise<br> participation or pose as unnecessary risk to the patient in the study, including,<br> but not limited, to the following: Unstable angina; Myocardial infarction =< 6<br> months prior to registration; Serious uncontrolled cardiac arrhythmia; Uncontrolled<br> diabetes<br><br> - Any concurrent severe and/or uncontrolled medical conditions which could compromise<br> participation or pose as unnecessary risk to the patient in the study, including,<br> but not limited, to the following: Interstitial pneumonia or extensive and<br> symptomatic interstitial fibrosis of the lung; QTc > 500 msec; Patients who require<br> chronic treatment with PPI or H2 antagonist<br><br> - Impairment of gastrointestinal (GI) function or GI disease that may significantly<br> alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled<br> nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability<br> to swallow the tablets)<br><br> - Known standard therapy for the patient's disease that is potentially curative or<br> definitely capable of extending life expectancy<br><br> - Chemotherapy =< 3 weeks; Mitomycin C/nitrosoureas =< 6 weeks; Immunotherapy =< 2<br> weeks; Biologic therapy =< 2 weeks; Prior investigational therapy =< 4 weeks; Full<br> field radiation therapy =< 4 weeks or limited field radiation therapy =< 2 weeks;<br> Radiation to > 30% of bone marrow; Major surgery (i.e., laparotomy) =< 4 weeks; or<br> Minor surgery =< 2 weeks prior to registration<br><br> - Any of the following: pregnant women; nursing women; men or women of childbearing<br> potential who are unwilling to employ adequate barrier contraception<br><br> - Patients on whom DCE-MRI is contraindicated (e.g., presence of MRI-incompatible<br> metallic implants or prosthetic heart valves, pacemakers, etc.) are ineligible<br><br> - ECOG performance status (PS) 3 or 4<br><br> - Treatment with medications listed in Appendix I for which no safer or more<br> efficacious alternative is available<br><br> - Uncontrolled infection<br><br> - Failure to fully recover from acute, reversible effects of prior chemotherapy<br> regardless of interval since last treatment

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06);Toxicity associated with everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06);Therapeutic antitumor activity of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06);Recommended phase II dose (RP2D) of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06);Biological activity and therapeutic antitumor activity of everolimus and vatalanib when given at the MTD/RPTD (Cohort II);Evaluation of pharmacogenetic, metabolic, and clinical markers that may predict hypertension induced by anti-VEGF therapy (Cohort II);Efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine carcinoma, non-small cell lung cancer, or melanoma (Cohort II)