A Two Steps Phase I Trial of Pazopanib or Pemetrexed in Combination With Crizotinib Followed by the Triplet, Crizotinib Plus Pazopanib Plus Pemetrexed in Patients With Advanced Malignancies

NCT01548144 Phase 1 TERMINATED

The goal of this clinical research study is to find the highest tolerable dose of the combination of Xalkori (crizotinib) either with Votrient (pazopanib) or Alimta (pemetrexed) or of the combination of 3 study drugs that can be given to patients with advanced cancer. The safety of these drug combinations will also be studied. Crizotinib is designed to block a protein called ALK, which is involved in cancer cell growth and survival. Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells. Pemetrexed is designed to block proteins that may cause tumors to grow. This is an investigational study. Crizotinib is FDA approved and commercially available for the treatment of locally advanced or metastatic non-small cell lung cancer. Pazopanib is FDA approved and commercially available for treatment of advanced renal cell carcinoma. Pemetrexed is FDA approved and commercially available for the treatment of non-small cell lung cancer. The combination of crizotinib with pazopanib, crizotinib with pemetrexed, pazopanib with pemetrexed, and giving all 3 drugs together to patients with advanced cancer is investigational. Up to 364 patients will take part in this study. All will be enrolled at MD Anderson.

Details

Lead sponsor	M.D. Anderson Cancer Center
Phase	Phase 1
Status	TERMINATED
Enrolment	178
Start date	2012-04
Completion	2021-08-26

Conditions

• Advanced Cancers

Interventions

• Crizotinib (Xalkori)
• Pazopanib
• Pemetrexed

Primary outcomes

• Maximum Tolerated Dose (MTD) of Crizotinib and Pazopanib — 4 weeks
  If not more than 33% of participants in cohort develop dose limiting toxicity (DLT), this cohort considered MTD. MTD defined by DLTs that occur in first cycle (4 weeks). DLT defined as: Clinically grade 3 or 4 non-hematologic toxicity. Grade 4 hematologic toxicity lasting 3 weeks or longer. Grade 4 nausea or vomiting \> 5 days despite maximum anti-nausea regimens. Grade 3 non-hematologic toxicity including symptoms/signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complication or abnormality not defined in the NCI-CTCAE v4.0 attributable to therapy.

Countries

United States