A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01712217
First received: October 11, 2012
Last updated: July 14, 2015
Last verified: January 2015
  Purpose

The purpose of the study is to evaluate safety and efficacy of AT13387 Alone and in Combination with Crizotinib in the Treatment of Non-small Cell Lung Cancer.


Condition Intervention Phase
Non-small Cell Lung Cancer(NSCLC)
Drug: AT13387
Drug: Crizotinib
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by Astex Pharmaceuticals:

Primary Outcome Measures:
  • Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    - Number of patients with adverse events

  • Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    - Change in tumor measurements by RECIST 1.1 every 8 weeks

  • Part C: The objective overall response rate for AT13387 alone and the objective response rate (CR+PR) for AT13387 + crizotinib at Stage 1 and Stage 2 of the Simon's 2-stage design. [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    - Change in tumor measurements by RECIST 1.1 every 8 weeks


Secondary Outcome Measures:
  • Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • Area under the plasma concentration versus time curve (AUC) of AT13387 and crizotinib alone and in combination Week 4
    • Maximum concentration (Cmax) OF AT13387 and crizotinib alone and in combination by Week 4

  • Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    • Change in tumor measurements by RECIST 1.1 every 8 weeks
    • Change in CTCs from baseline every 4 weeks
    • Assessment of PFS and OS as measured by weeks

  • Part B: Assess safety of AT13387 in combination with crizotinib; compare PFS and OS between crizotinib and crizotinib + AT13387; and assess overall response rate (CR + PR) in crizotinib patients who crossover to crizotinib + AT13387 [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    • Number of patients with adverse events
    • PFS and OS as measured in weeks
    • Response rate as measured by RECIST 1.1 every 8 weeks

  • Part C: Assess safety of AT13387 alone and in combination with crizotinib who progressed on crizotinib treatment; and compare the PFS and OS of AT13387 administered alone or in combination with crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: Yes ]
    • Number of patients with adverse events
    • PFS and OS as measured in weeks


Estimated Enrollment: 228
Study Start Date: October 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AT13387 and Crizotinib
Part A is a single-arm, Phase 1, open-label, dose-escalation design in patients with NSCLC who have already been receiving crizotinib 250 mg by mouth (PO) twice daily (BID) for at least 8 weeks and are still tolerating treatment at that dose. Patients will continue treatment with crizotinib + escalating doses of AT13387 IV weekly for 3 weeks in a 4-week cycle. Each cohort will consist of at least 6 patients until the maximum tolerated dose (MTD) is reached. An additional 12 patients will be treated at the MTD level of AT13387 in combination with crizotinib to confirm the safety profile of the combination at that dose level.
Drug: AT13387
HSP90 inhibitor
Drug: Crizotinib
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Other Name: Xalkori
Active Comparator: Crizotinib versus crizotinib + AT13387
Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the MTD established in Part A. Part B will enroll 128 patients with NSCLC who have been treated with crizotinib for at least 8 weeks and are still tolerating treatment without evidence of disease progression.
Drug: AT13387
HSP90 inhibitor
Drug: Crizotinib
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Other Name: Xalkori
Active Comparator: AT13387 or AT13387 + crizotinib
Part C is an open-label, randomized, Phase 2, Simon's 2-stage design of AT13387 administered alone once weekly for 3 weeks (QW×3) or in combination with crizotinib at the MTD established in Part A.
Drug: AT13387
HSP90 inhibitor
Drug: Crizotinib
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Other Name: Xalkori

Detailed Description:

This is a 3-part phase 1-2 study in patients with anaplastic lymphoma kinase (ALK) + or other potentially crizotinib-sensitive NSCLC who have been receiving crizotinib. Part A is a single-arm, Phase 1, open-label, dose escalation design in patients with NSCLC who have already been receiving crizotinib for at least 8 weeks and continue to tolerate therapy. Part B is a Phase 2, open-label, randomized continuation design comparing crizotinib alone versus the combination of crizotinib + AT13387 at the maximum tolerated dose established in Part A. Part C is an open-label, randomized, Phase 2, Simon's 2 stage design evaluating single agent AT13387 or combination AT13387 + crizotinib at the MTD established in Part A in patients who progressed on crizotinib at any time.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men or women 18 years of age or older
  2. Must have Non-small Cell Lung Cancer with ALK+ mutation or other mutations or rearrangements potentially sensitive to crizotinib
  3. Measurable disease
  4. Must have been receiving or have received crizotinib
  5. Have adequate cardiac, bone marrow, liver and kidney function
  6. Must be willing and able to provide written informed consent and comply with the protocol and study procedures

Exclusion Criteria:

  1. Prior anti-cancer treatment with any HSP90 inhibitor
  2. Have received chemotherapy, radiation therapy or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug
  3. Prior malignancy other than adequately treated basal or squamous cell carcinoma of the skin, superficial bladder cancer, low-grade cervical cancer, non-metastatic prostate cancer, or have been disease-free for at least 3 years
  4. Abnormal heart function
  5. Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
  6. Hypersensitivity of AT13387 or other components of the drug product
  7. Treatment with an investigational drug within 3 weeks prior to the first dose of study drug
  8. Severe systemic diseases or active uncontrolled infections
  9. Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus
  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: NCT01712217

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic-Scottsdale
Scottsdale, Arizona, United States, 85259
United States, California
University of California, San Diego Medical Center
La Jolla, California, United States, 92093-0698
UCLA Medical Center
Los Angeles, California, United States, 90095
USC Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
Sharp Clinical Oncology Research-Sharp Memorial Hospital
San Diego, California, United States, 92123
Innovative Clinical Research Institute
Whittier, California, United States, 90603
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine-Yale Cancer Center
New Haven, Connecticut, United States, 06519
United States, Delaware
Christiana Hospital
Newark, Delaware, United States, 19713
United States, Florida
Florida Hospital Cancer Institute
Orlando, Florida, United States, 32804
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612-9497
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Northwestern University The Feinberg School of Medicine
Chicago, Illinois, United States, 60611
United States, Michigan
University of Michigan Medical Center
Ann Arbor, Michigan, United States, 48109
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, Minnesota
Mayo Clinic-Rochester
Rochester, Minnesota, United States, 55905
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Nebraska
University of Nebraska Medical Center Eppley Cancer Center
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461
Columbia University Medical Center
New York, New York, United States, 10032
United States, North Carolina
Cone Health Cancer Center
Greensboro, North Carolina, United States, 27409
United States, Ohio
Oncology Hematology in Cincinnati
Cincinnati, Ohio, United States, 45242
University of Cincinnati Cancer Institute
Cincinnati, Ohio, United States, 45267
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
United States, Oregon
Providence Portland Medical Center
Portland, Oregon, United States, 97213
United States, Pennsylvania
The Pennsylvania State University-Penn State
Hershey, Pennsylvania, United States, 17033-0850
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
The West Clinic
Memphis, Tennessee, United States, 38120
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390
United States, Virginia
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
United States, Washington
Swedish Cancer Institute
Seattle, Washington, United States, 98104
University of Washington Medical Center
Seattle, Washington, United States, 98109
United States, Wisconsin
University of Wisconsin-Carbone Cancer Center
Madison, Wisconsin, United States, 53579
Canada, Nova Scotia
Atlantic Clinical Cancer Research Unit
Halifax, Nova Scotia, Canada, B3H 1V7
Canada
McGill University Health Center
Montreal, Quebec, Canada, H3A 1A1
Institut Universitaire de Cardiologie et de Pneumologie De Quebec
Sainte-Foy, Quebec, Canada, G1V 4G5
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Cancer Care Manitoba
Winnipeg, Canada, R3E OV9
France
Centre Hospitalier Regional Universitaire Besancon
Besancon Cedex, France, 25030
CHU de Caen-Hopital Cote de Nacre
Caen, France, 14033
Hopital Saint Antoine
Creteil Cedex, France, 94010
Centre Hospitalier de Grenoble
Grenoble, France, 38043
CHRU de Lille
Lille cedex, France, 59037
Institut Paoli-Calmettes
Marseille, France, 13273
Hopital Tenon
Paris, France, 75020
Centre Hospitalier Lyon Sud
Pierre-Benite Cedex, France, 69495
CHU Toulouse-Hopital Larrey
Toulouse, France, 31 059
Institut Gustave Roussy
Villejuif, France, 94800
Korea, Republic of
Chungbuk National University Hospital
Cheongju-si, Korea, Republic of, 362-711
The Catholic University of Korea, St. Vincent's Hospital
Gyeonggi-do, Korea, Republic of, 442-723
Chonnam National University Hwasun Hospital
Hwasun-gun Jeonnam, Korea, Republic of, 519-809
National Cancer Center
Korea, Korea, Republic of, 410-769
Seoul National University Bundang Hospital
Seongnam, Korea, Republic of, 463-707
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Samsung Medical Center
Seoul, Korea, Republic of, 135-710
Severance Hospital, Yonsei University Health System
Seoul, Korea, Republic of, 120-752
Spain
Hospital Germans Trias i Pujol
Badalona, Spain, 08916
Hospital Universitari Quiron Dexeus Barcelona
Barcelona, Spain, 08028
Centro Integral Oncologico Clara Campal
Madrid, Spain, 28050
Hospital Regional Universitario de Malaga
Malaga, Spain, 29010
Sponsors and Collaborators
Astex Pharmaceuticals
Investigators
Principal Investigator: Jean-Charles Soria, MD Gustave Roussy, Cancer Campus, Grand Paris
  More Information

No publications provided

Responsible Party: Astex Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01712217     History of Changes
Other Study ID Numbers: AT13387-05, 2012-001575-37
Study First Received: October 11, 2012
Last Updated: July 14, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Astex Pharmaceuticals:
Non-small cell lung cancer

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Crizotinib
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 28, 2015