Clinical Trial: Everolimus and Vatalanib in Treating Patients With Advanced Solid Tumors

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: 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

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.


Detailed Summary:

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 th
Sponsor: Mayo Clinic

Current Primary Outcome:

  • Maximum tolerated dose of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06) [ Time Frame: Up to 28 days post treatment cycle ]
  • Toxicity associated with everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06) [ Time Frame: Up to 28 days post treatment cycle ]
  • Therapeutic antitumor activity of everolimus and vatalanib (Cohort I) (Closed to enrollment as of 12/6/06) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Post treatment cycle ]
  • Evaluation of pharmacogenetic, metabolic, and clinical markers that may predict hypertension induced by anti-VEGF therapy (Cohort II) [ Time Frame: 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) [ Time Frame: Post treatment cycle with MTD outcomes ]


Original Primary Outcome:

  • Maximum tolerated dose of everolimus and vatalanib (Cohort 1) (Closed to enrollment as of 12/6/06)
  • Toxicity associated with everolimus and vatalanib (Cohort 1) (Closed to enrollment as of 12/6/06)
  • Therapeutic antitumor activity of everolimus and vatalanib (Cohort 1) (Closed to enrollment as of 12/6/06)
  • Recommended phase II dose (RPTD) of everolimus and vatalanib (Cohort 1) (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 2)
  • Evaluation of pharmacogenetic, metabolic, and clinical markers that may predict hypertension induced by anti-VEGF therapy (Cohort 2)
  • Efficacy outcomes in patients with metastatic kidney cancer, neuroendocrine carcinoma, non-small cell lung cancer, or melanoma (Cohort 2)


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Mayo Clinic

Dates:
Date Received: April 9, 2008
Date Started: December 2004
Date Completion: December 2017
Last Updated: March 21, 2017
Last Verified: March 2016