Pazopanib or Pemetrexed and Crizotinib in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01548144
First received: March 5, 2012
Last updated: July 3, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Advanced Cancers
Drug: Crizotinib (Xalkori)
Drug: Pazopanib
Drug: Pemetrexed
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Crizotinib and Pazopanib [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 364
Study Start Date: April 2012
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Crizotinib (Xalkori) + Pazopanib

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Drug: Crizotinib (Xalkori)

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Other Names:
  • PF-02341066
  • Xalkori
Drug: Pazopanib

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Other Name: GW786034
Experimental: Crizotinib (Xalkori) + Pemetrexed

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Pemetrexed: 200 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Drug: Crizotinib (Xalkori)

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Other Names:
  • PF-02341066
  • Xalkori
Drug: Pemetrexed

Starting dose for Pemetrexed: 200 mg/m2 by vein on Day 1 of a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Starting dose for Pemetrexed: 400 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Other Names:
  • LY231514
  • Alimta
  • MTA
  • Multitargeted Antifolate
  • NSC-698037
Experimental: Pazopanib + Pemetrexed

Starting dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Starting dose for Pemetrexed: 200 mg/m2 by vein on Day 1 of a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Drug: Pazopanib

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Other Name: GW786034
Drug: Pemetrexed

Starting dose for Pemetrexed: 200 mg/m2 by vein on Day 1 of a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Starting dose for Pemetrexed: 400 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Other Names:
  • LY231514
  • Alimta
  • MTA
  • Multitargeted Antifolate
  • NSC-698037
Experimental: Crizotinib (Xalkori) + Pazopanib + Pemetrexed

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Starting dose for Pemetrexed: 400 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Drug: Crizotinib (Xalkori)

Starting dose for Crizotinib: 250 mg by mouth every other day, 1 or 2 times a day on Day 1 of a 21 day cycle. Participant told how often to take this drug.

Dose Expansion Group: MTD from Phase 1.

Other Names:
  • PF-02341066
  • Xalkori
Drug: Pazopanib

Starting Dose for Pazopanib: 200 mg by mouth daily in a 21 day cycle.

Dose Expansion Group: MTD from Phase 1.

Other Name: GW786034
Drug: Pemetrexed

Starting dose for Pemetrexed: 200 mg/m2 by vein on Day 1 of a 21 day cycle.

Expansion group starting dose: MTD from Phase 1.

Starting dose for Pemetrexed: 400 mg/m2 by vein every 3 weeks on Day 1 of a 21 day cycle.

Other Names:
  • LY231514
  • Alimta
  • MTA
  • Multitargeted Antifolate
  • NSC-698037

  Show Detailed Description

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with advanced cancer, either refractory to standard therapy or for which no effective standard therapy that increases survival for at least 3 months is available.
  2. Patients must have measurable or evaluable disease, as defined by RECIST 1.1.
  3. Women of child-bearing potential and men must agree to use adequate contraception.
  4. ECOG performance status of 0 to 2.
  5. Adequate organ functions: (Crizotinib plus Pazopanib arm A): Neutrophils > 1000/uL; Platelets ≥ 75,000/uL; Total bilirubin < or= 2 x ULN (upper limit of normal); ALT < or = 2.5 x ULN or < o r= 5 x ULN if liver metastases persist; Serum creatinine < 2 x ULN (Crizotinib plus Pemetrexed arm B, Pazopanib plus Pemetrexed arm C, Crizotinib plus Pazopanib plus Pemetrexed arm D) Neutrophils > 1500/uL; Platelets > or = 100,000/uL; Total bilirubin < or = 2 x ULN (upper limit of normal); ALT < or = 2.5 x ULN or < or = 5 x ULN if liver metastases persist; Calculated GFR > 45 mL/min.
  6. Creatinine Clearance: The standard Cockcroft and Gault formula must be used to calculate CrCl for enrollment or dosing. Also include in the pre-treatment or baseline text portion of the protocol, the 'On Study Evaluations or During Treatment' for every Pemetrexed treatment day, and also capture in the study Schedule of Events. No dosage adjustment is needed in patients with creatinine clearance > 45 mL/min. Insufficient numbers of patients have been studied with creatinine clearance <45 mL/min to give a dose recommendation. Therefore, Pemetrexed should not be administered to patients whose creatinine clearance is <45 mL/min.
  7. For pemetrexed arms: The ability to interrupt NSAIDs 2 days before (5 days for long-acting NSAIDs), the day of, and 2 days following administration of Pemetrexed.
  8. The ability to take folic acid, Vitamin B12, and dexamethasone according to protocol for all pemetrexed arms.
  9. Expansion cohort only for arms containing crizotinib: arm A (Crizotinib plus Pazopanib) and arm B (Crizotinib plus Pemetrexed) and arm D (Crizotinib plus Pazopanib Plus Pemetrexed) but not arm C (Pazopanib plus Pemetrexed). Patients must have ALK abnormality including: translocation, ALK amplification, mutation and overexpression as determined by FISH, IHC, qPCR, qRT-PCR, array Comparative Genomic Hybridization or direct sequencing (aCGH). Or patients must have a c-Met abnormality; either c-Met amplification or c-Met mutation or patients must have the ROS1 translocation as determined by FISH.

Exclusion Criteria:

  1. Patient receiving any concurrent chemotherapy.
  2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring intravenous antibiotics.
  3. Symptomatic congestive heart failure (NYHA Class III or IV), unstable angina pectoris or congenital long QT syndrome.
  4. Medical and/or psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
  5. Known anaphylactic or severe hypersensitivity to study drugs or their analogs.
  6. Patient has failed to recover from any prior surgery within 4 weeks of study entry.
  7. Patient is pregnant or lactating.
  8. Patient has had any treatment specific for tumor control within 3 weeks of dosing with investigational drugs and cytotoxic agents, or within 2 weeks of cytotoxic agent given weekly, or within 6 weeks of nitrosoureas or mitomycin C, or within 5 half-lives of biological targeted agents with half-lives and pharmacodynamic effects lasting less than 5 days (that includes, but is not limited to, erlotinib, sorafenib, sunitinib, bortezomib, and other similar agents).
  9. Patient has any signs of intestinal obstruction.
  10. Patient is not able to swallow oral medication.
  11. Patients receiving whole brain radiation within 14 days prior to the first dose of study drugs will be excluded. NOTE: Patients receiving palliative radiation (other than whole brain) before or during treatment may still be eligible as long as there are evaluable lesions that are not being irradiated.
  12. Pemetrexed arms only: Presence of third space fluid which cannot be controlled by drainage.
  13. Additional Exclusions for the 3 pazopanib containing arms (Crizotinib plus Pazopanib) and (Pazopanib plus Pemetrexed) and (Crizotinib plus Pazopanib plus Pemetrexed). 1. History of stroke or transient ischemic attack within 6 months prior to study enrollment. 2. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment. 3. Urine for proteinuria > or = 2+ (patients discovered to have > or = 2+ proteinuria on urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate < or = 1g of protein in 24 hours to be eligible).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01548144

Contacts
Contact: Ralph Zinner, MD, BA 713-563-1930

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Ralph Zinner, MD,BA UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01548144     History of Changes
Other Study ID Numbers: 2011-1142, NCI-2012-00324
Study First Received: March 5, 2012
Last Updated: July 3, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancies
Crizotinib
PF-02341066
Pazopanib
Gw786034
Pemetrexed
LY231514
Alimta
MTA
Multitargeted Antifolate
NSC-698037

Additional relevant MeSH terms:
Neoplasms
Folic Acid Antagonists
Pemetrexed
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on July 29, 2014