Dasatinib and Crizotinib in Advanced Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by M.D. Anderson Cancer Center
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01744652
First received: December 5, 2012
Last updated: May 19, 2014
Last verified: May 2014
  Purpose

The goal of this clinical research study is to find the highest tolerable dose of the combination of dasatinib and crizotinib that can be given to patients with advanced cancer. The safety of this drug combination will also be studied.

Dasatinib is designed to block certain proteins from causing cancer cells to grow out of control. This may cause the cancer cells to die.

Crizotinib is designed to block certain abnormal genes found in cancer cells. This may cause the cancer cells to die.


Condition Intervention Phase
Advanced Cancers
Drug: Crizotinib
Drug: Dasatinib
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 Phase I Trial of Dasatinib in Combination With Crizotinib 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 Dasatinib plus Crizotinib [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
    Maximum tolerated dose (MTD) defined by dose limiting toxicities (DLTs) that occur during the first cycle (first four weeks). MTD defined as the highest dose studied in which the incidence of DLT was less than 33%.


Secondary Outcome Measures:
  • Tumor Response [ Time Frame: After 2, 28 day cycles ] [ Designated as safety issue: Yes ]
    Tumor response defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, (3) decrease in tumor markers by more than or equal to 25% (for example, a >/= 25% decrease in cancer antigen 125 (CA125) for patients with ovarian cancer), or (4) a partial response according to the Choi criteria, i.e. decrease in size by 10% or more, or a decrease in the tumor density, as measured by Hounsfield units (HU), by more than or equal to 15%.


Estimated Enrollment: 176
Study Start Date: March 2013
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A - Crizotinib + Dasatinib

Arm A: Patients receive dose of crizotinib plus an increasing dose of dasatinib. All participants take dasatinib by mouth 1 time each day. Patients take this drug alone on Day 1 of Cycle 1, before the first day they receive the study drug combination. Final dose level in both arms (dose level number 5) is identical. In the case that both arms define dose level 5 as the MTD, then the expansion cohort for safety will include 10 patients with that dose. If two different MTDs on both arms defined, then both MTDs cohorts expanded with 10 patients and 20 patients included on the safety expansion analysis.

Crizotinib dose: 250 mg by mouth twice a day in a 28 day cycle. Dasatinib starting dose: 50 mg by mouth daily in a 28 day cycle.

Crizotinib Expansion dose: 250 mg by mouth twice a day in a 28 day cycle. Dasatinib Expansion Dose: MTD from dose escalation group.

Drug: Crizotinib

Arm A Crizotinib dose: 250 mg by mouth twice a day in a 28 day cycle. Crizotinib Expansion dose: 250 mg by mouth twice a day in a 28 day cycle.

Arm B Crizotinib starting dose: 250 mg by mouth every other day in a 28 day cycle. Crizotinib Expansion Dose: MTD from dose escalation group.

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

Arm A Dasatinib starting dose: 50 mg by mouth daily in a 28 day cycle. Arm A Dasatinib Expansion Dose: MTD from dose escalation group.

Arm B Dasatinib dose: 140 mg by mouth daily in a 28 day cycle. Arm B Dasatinib Expansion Dose: 140 mg by mouth daily in a 28 day cycle.

Other Names:
  • BMS-354825
  • Sprycel
Experimental: Arm B - Dasatinib + Crizotinib

Arm B: Patients receive dasatinib plus an increasing dose of crizotinib. All participants take dasatinib by mouth 1 time each day. Patients take this drug alone on Day 1 of Cycle 1, before the first day they receive the study drug combination. Final dose level in both arms (dose level number 5) is identical. In the case that both arms define dose level 5 as the MTD, then the expansion cohort for safety will include 10 patients with that dose. If two different MTDs on both arms defined, then both MTDs cohorts expanded with 10 patients and 20 patients included on the safety expansion analysis.

Dasatinib 140 mg by mouth daily in a 28 day cycle. Crizotinib starting dose: 250 mg by mouth every other day in a 28 day cycle.

Dasatinib Expansion Dose: 140 mg by mouth daily in a 28 day cycle. Crizotinib Expansion Dose: MTD from dose escalation group.

Drug: Crizotinib

Arm A Crizotinib dose: 250 mg by mouth twice a day in a 28 day cycle. Crizotinib Expansion dose: 250 mg by mouth twice a day in a 28 day cycle.

Arm B Crizotinib starting dose: 250 mg by mouth every other day in a 28 day cycle. Crizotinib Expansion Dose: MTD from dose escalation group.

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

Arm A Dasatinib starting dose: 50 mg by mouth daily in a 28 day cycle. Arm A Dasatinib Expansion Dose: MTD from dose escalation group.

Arm B Dasatinib dose: 140 mg by mouth daily in a 28 day cycle. Arm B Dasatinib Expansion Dose: 140 mg by mouth daily in a 28 day cycle.

Other Names:
  • BMS-354825
  • Sprycel

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must have histologically confirmed solid malignancy that is metastatic or unresectable or lymphoma, for which standard curative or palliative measures that improve survival by at least three months do not exist or are no longer effective. For the purpose of this study patients with leukemia are not eligible.
  2. Age >/= 16 years.
  3. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status </= 2.
  4. Patients must have normal organ and marrow function as followed defined: ANC >/= 1,000/mcL; Plt >/=75,000/mcL; total bilirubin </=2.0 mg/dL; AST (TGO)/ALT (TGP) </=2.5x upper limit of normal; if liver metastasis are present, then </= 5.0x upper limit; estimated creatinine clearance by Cockcroft-Gault equation > 30 mL/min
  5. The effects of Dasatinib and Crizotinib on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  6. Patients receiving palliative radiation will be eligible after a wash-out period of 2 weeks between finishing radiation and initiation of study drugs. Palliative radiation will not be allowed during cycle 1 of treatment but is permitted in this study during following cycles as long as there are evaluable lesions that are not being irradiated
  7. Signed informed consent approved by the Institutional Review Board prior to patient entry.
  8. Expanded cohort only: Cohort 1: patients with predominant metastatic bone disease; Cohort 2: patients with primary squamous head and neck cancers; Cohort 3: patients presenting any molecular abnormality of interest, which can include an ALK translocation, ALK amplification, ALK mutation and overexpression as determined by FISH, IHC, qPCR, qRT-PCR, array Comparative Genomic Hybridization or direct sequencing (aCGH); a c-MET abnormality, either c-MET amplification by FISH, overexpression by IHC or c-MET mutation; BRAF, DDR2 and CDKN2A mutations; and, finally, TRIM 16 expression and CCN2 expression.

Exclusion Criteria:

  1. Patient receiving any concurrent chemotherapy.
  2. Concurrent severe and/or uncontrolled medical disease including, but not limited to, ongoing or active infection requiring intravenous antibiotics.
  3. Symptomatic congestive heart failure (NYHA Class III or IV), or unstable angina pectoris.
  4. Presence of symptomatic pleural and/or pericardial effusion not appropriated treated.
  5. Prolonged QTc interval (>/=500 msec), as calculated by Bazett`s formula.
  6. Psychiatric problems of sufficient severity to limit full compliance with the study or expose patients to undue risk.
  7. Known anaphylactic or severe hypersensitivity to Dasatinib or Crizotinib or their analogs.
  8. Patient has failed to recover from any prior surgery within 4 weeks of study entry.
  9. Patient is pregnant or lactating. Pregnant women are excluded from this study because dasatinib and crizotinib are agents with the potential for teratogenic or abortifacient effects (Pregnancy category D).
  10. 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.
  11. Patient is not able to swallow oral medication.
  12. Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 complex are ineligible.
  13. Patients with known pulmonary hypertension.
  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: NCT01744652

Contacts
Contact: David S. Hong, MD 713-763-1930

Locations
United States, Texas
UT MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Pfizer
Investigators
Principal Investigator: David S. Hong, MD UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01744652     History of Changes
Other Study ID Numbers: 2012-0721, NCI-2013-00071
Study First Received: December 5, 2012
Last Updated: May 19, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:
Advanced Cancers
Advanced Malignancies
Unresectable
Metastatic
Crizotinib
PF-02341066
Xalkori
Dasatinib
BMS-354825
Sprycel

Additional relevant MeSH terms:
Neoplasms
Dasatinib
Crizotinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014