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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Astex Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Astex Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01712217
First received: October 11, 2012
Last updated: September 26, 2014
Last verified: September 2014
  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: February 2016
Estimated Primary Completion Date: June 2015 (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

Contacts
Contact: Medpace Recruitment, Center 1-866-872-2349 recruitment@medpace.com

  Hide Study Locations
Locations
United States, Arizona
Mayo Clinic-Scottsdale Recruiting
Scottsdale, Arizona, United States, 85259
Principal Investigator: Helen Ross, MD         
United States, California
University of California, San Diego Medical Center Recruiting
La Jolla, California, United States, 92093-0698
Principal Investigator: Lyudmila Bazhenova, MD         
USC Norris Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90033
Principal Investigator: Barbara Gitlitz, MD         
Sharp Clinical Oncology Research-Sharp Memorial Hospital Recruiting
San Diego, California, United States, 92123
Principal Investigator: David Bodkin, MD         
UCLA Medical Center Recruiting
Santa Monica, California, United States, 90404
Principal Investigator: Jonathan Goldman, MD         
Innovative Clinical Research Institute Recruiting
Whittier, California, United States, 90603
Principal Investigator: Merrill Shum, MD         
United States, Colorado
University of Colorado Denver Recruiting
Aurora, Colorado, United States, 80045
Principal Investigator: Ross Camidge         
United States, Connecticut
Yale University School of Medicine-Yale Cancer Center Recruiting
New Haven, Connecticut, United States, 06519
Principal Investigator: Scott Gettinger, MD         
United States, Delaware
Christiana Hospital Recruiting
Newark, Delaware, United States, 19713
Principal Investigator: Michael Guarino         
United States, Florida
Florida Hospital Cancer Institute Recruiting
Orlando, Florida, United States, 32804
Principal Investigator: Tarek Mekhail         
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612-9497
Principal Investigator: Alberto Chiappori, MD         
United States, Illinois
Northwestern University The Feinberg School of Medicine Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Jyoti Patel         
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Ravi Salgia, MD         
United States, Indiana
Indiana University Melvin and and Bren Simon Cancer Center Withdrawn
Indianapolis, Indiana, United States, 46202
United States, Michigan
University of Michigan Medical Center Not yet recruiting
Ann Arbor, Michigan, United States, 48109
Principal Investigator: Gregory Kalemkerian, MD         
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Principal Investigator: Antoinette Wozniak, MD         
United States, Minnesota
Mayo Clinic-Rochester Recruiting
Rochester, Minnesota, United States, 55905
Principal Investigator: Julian Molina         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Principal Investigator: Maria Baggstrom         
United States, Nebraska
University of Nebraska Medical Center Eppley Cancer Center Recruiting
Omaha, Nebraska, United States, 68198
Principal Investigator: Apar Ganti, MD         
United States, New Hampshire
Dartmouth Hitchcock Medical Center Recruiting
Lebanon, New Hampshire, United States, 03756
Principal Investigator: Konstantin Dragnev, MD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10461
Principal Investigator: Bilal Piperdi, MD         
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Principal Investigator: Balazs Halmos, MD         
United States, North Carolina
Duke University Medical Center Withdrawn
Durham, North Carolina, United States, 27710
Cone Health Cancer Center Recruiting
Greensboro, North Carolina, United States, 27409
Principal Investigator: Mohamed Mohamed, MD         
Wake Forest Baptist Health-Wake Forest University School of Medicine Not yet recruiting
Winston Salem, North Carolina, United States, 27157
Principal Investigator: William Petty, MD         
United States, Ohio
Oncology Hematology in Cincinnati Recruiting
Cincinnati, Ohio, United States, 45242
Principal Investigator: David Waterhouse, MD         
University of Cincinnati Cancer Institute Recruiting
Cincinnati, Ohio, United States, 45267
Principal Investigator: Nagla Karim         
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Principal Investigator: Nathan Pennell, MD         
Ohio State University Medical Center Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: Erin Bertino, MD         
United States, Oregon
Providence Portland Medical Center Recruiting
Portland, Oregon, United States, 97213
Principal Investigator: Rachel Sanborn, MD         
United States, Pennsylvania
The Pennsylvania State University-Penn State Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Principal Investigator: Chandra Prakash Belani, MD         
Thomas Jefferson University Recruiting
Philadelphia, Pennsylvania, United States, 19107
Principal Investigator: Barbara Campling         
United States, Tennessee
The West Clinic Recruiting
Memphis, Tennessee, United States, 38120
Principal Investigator: Daruka Mahadevan, MD         
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Principal Investigator: David Spigel, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Principal Investigator: Joan Schiller, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alexander Spira, MD         
United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98109
Principal Investigator: Renato Martins         
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Principal Investigator: Howard West, MD         
United States, Wisconsin
University of Wisconsin-Carbone Cancer Center Recruiting
Madison, Wisconsin, United States, 53579
Principal Investigator: Ticiana Leal, MD         
Canada, Nova Scotia
Atlantic Clinical Cancer Research Unit Not yet recruiting
Halifax, Nova Scotia, Canada, B3H 1V7
Principal Investigator: Wojciech Morzycki         
Canada
McGill University Health Center Not yet recruiting
Montreal, Quebec, Canada, H3A 1A1
Principal Investigator: Vera Hirsh         
Institut Universitaire de Cardiologie et de Pneumologie De Quebec Not yet recruiting
Sainte-Foy, Quebec, Canada, G1V 4G5
Principal Investigator: Lise Tremblay         
Princess Margaret Hospital Not yet recruiting
Toronto, Ontario, Canada, M5G 2M9
Principal Investigator: Geoffrey Liu, MD         
Cancer Care Manitoba Not yet recruiting
Winnipeg, Canada, R3E OV9
Principal Investigator: Shantanu Banerji         
France
Centre Hospitalier Regional Universitaire Besancon Recruiting
Besancon Cedex, France, 25030
Principal Investigator: Virginie Westeel, MD         
CHU de Caen-Hopital Cote de Nacre Recruiting
Caen, France, 14033
Principal Investigator: Gerard Zalcman, MD         
Hopital Saint Antoine Not yet recruiting
Creteil Cedex, France, 94010
Principal Investigator: Christos Chouaid         
Centre Hospitalier de Grenoble Recruiting
Grenoble, France, 38043
Principal Investigator: Denis Moro-Sibilot         
CHRU de Lille Recruiting
Lille cedex, France, 59037
Principal Investigator: Alexis Cortot, MD         
Institut Paoli-Calmettes Recruiting
Marseille, France, 13273
Principal Investigator: Anne Madroszyk, MD         
Hopital Tenon Recruiting
Paris, France, 75020
Principal Investigator: Marie Wislez, MD         
Centre Hospitalier Lyon Sud Recruiting
Pierre-Benite Cedex, France, 69495
Principal Investigator: Pierre-Jean Souquet         
CHU Toulouse-Hopital Larrey Recruiting
Toulouse, France, 31 059
Principal Investigator: Julien Mazieres, MD         
Institut Gustave Roussy Recruiting
Villejuif, France, 94800
Principal Investigator: Benjamin Besse, MD         
Korea, Republic of
Chonnam National University Hwasun Hospital Not yet recruiting
Hwasun-gun Jeonnam, Korea, Republic of, 519-809
Principal Investigator: In Jae Oh         
National Cancer Center Not yet recruiting
Korea, Korea, Republic of, 410-769
Principal Investigator: Ji-Youn HAN         
Seoul National University Bundang Hospital Not yet recruiting
Seongnam, Korea, Republic of, 463-707
Principal Investigator: Jong-Seok LEE         
Samsung Medical Center Not yet recruiting
Seoul, Korea, Republic of, 135-710
Principal Investigator: Myung-Ju Ahn         
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of, 138-736
Principal Investigator: Dae Ho Lee         
Severance Hospital, Yonsei University Health System Not yet recruiting
Seoul, Korea, Republic of, 120-752
Principal Investigator: Joo Hang Kim         
Spain
Hospital Germans Trias i Pujol Not yet recruiting
Badalona, Spain, 08916
Principal Investigator: Teresa Moran         
Hospital Universitari Quiron Dexeus Barcelona Not yet recruiting
Barcelona, Spain, 08028
Principal Investigator: Satiago Viteri         
Hospital Clinic San Carlos Not yet recruiting
Madrid, Spain, 28040
Principal Investigator: Javier Puente         
Centro Integral Oncologico Clara Campal Not yet recruiting
Madrid, Spain, 28050
Principal Investigator: Esther Holgado         
Hospital Regional Universitario de Malaga Not yet recruiting
Malaga, Spain, 29010
Principal Investigator: Manuel Cobo         
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: September 26, 2014
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 October 23, 2014