NCT00655655

Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

A Phase I Trial of the mTOR Inhibitor RAD001 in Combination With VEGF Receptor Tyrosine Kinase Inhibitor PTK787/ZK 222584 in Patients With Advanced Solid Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: Mayo Clinic · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

OBJECTIVES: I. To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of RAD001 and once daily PTK787 when given in combination. (Cohort IA) II. To describe the toxicities associated with the combination of RAD001 and once daily PTK787. (Cohort IA) III. To evaluate the therapeutic antitumor activity of the combination of once daily PTK787 with RAD001. (Cohort IA) IV. To determine the dose limiting toxicity (DLT) and maximally tolerated dose (MTD) of RAD001 and twice daily PTK787 when given in combination. (Cohort IB) V. To describe the toxicities associated with the combination of RAD001 and twice daily PTK787. (Cohort IB) VI. To evaluate the therapeutic antitumor activity of the combination of twice daily PTK787 with RAD001. (Cohort IB) VII. To determine the MTD-Recommended Phase 2 Dose (RP2D) based on the MTD for Cohorts IA and IB. (Cohorts IA \& IB) VIII. To investigate the biological activity of the combination of PTK787 with RAD001 at the MTD-RP2D. (Cohort II) IX. To evaluate the therapeutic antitumor activity of the combination of PTK787 with RAD001 at the MTD-RP2D. (Cohort II) X. To evaluate pharmacogenetic, metabolic and clinical markers that may predict for hypertension induced by anti-VEGF therapy. (Cohort II) XI. To obtain pilot data on efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine cancer, NSCLC or melanoma. (Cohort II) OUTLINE: Patients are assigned to 1 of 4 cohorts, according to their disease (cohort IA, IB, or IIA \[any histopathologic diagnosis\] vs cohort IIB \[metastatic kidney cancer, neuroendocrine cancer, melanoma, or non-small cell lung cancer). Patients are initially enrolled into cohorts IA and IB until the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) are determined. Once the MTD/RP2D of everolimus and vatalanib are determined, subsequent patients are enrolled and treated in expansion cohorts IIA or IIB. Cohorts 1A or 1B (dose escalation cohorts; closed to enrollment as of 12/6/06): Patients receive oral vatalanib once (cohort 1A) or twice (cohort 1B) daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib once (cohort 1A) or twice (cohort 1B) daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohort IIA (expansion cohort treated at the MTD/RP2D): Patients receive oral everolimus once daily for 14 days followed by a 7-day rest period. Patients then receive oral vatalanib twice daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib twice daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohort IIB (expansion cohort treated at the MTD/RP2D): Patients receive oral vatalanib twice daily on days 1-28 and oral everolimus once daily on days 15-28 of course 1. For all subsequent courses, patients receive oral vatalanib twice daily and oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3 months.

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

Interventions

Type	Name	Description
DRUG	everolimus	Given orally
DRUG	vatalanib	Given orally
OTHER	pharmacological study	Correlative study (Cohort IIA only)
OTHER	laboratory biomarker analysis	Correlative study (Cohorts IIA and IIB)
PROCEDURE	dynamic contrast-enhanced magnetic resonance imaging	Correlative study (Cohort IIA only)
PROCEDURE	ultrasound imaging	Correlative study (Cohorts IIA and IIB)

Timeline

• Start date: 2004-12-01
• Primary completion: 2009-09-15
• Completion: 2018-01-11
• First posted: 2008-04-10
• Last updated: 2024-08-21

Locations

1 site across 1 country: United States