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

Sponsor
Astex Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01712217
Collaborator
(none)
220
Enrollment
65
Locations
3
Arms
55.5
Duration (Months)
3.4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
220 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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)
Study Start Date :
Oct 1, 2012
Actual Primary Completion Date :
Dec 1, 2016
Actual Study Completion Date :
May 16, 2017

Arms and Interventions

Arm Intervention/Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • Xalkori

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. [12 months]

      - Number of patients with adverse events

    2. Part B: The comparison of objective response rate by RECIST 1.1 between crizotinib alone and the combination of crizotinib + AT13387. [18 months]

      - Change in tumor measurements by RECIST 1.1 every 8 weeks

    3. 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. [18 months]

      - Change in tumor measurements by RECIST 1.1 every 8 weeks

    Secondary Outcome Measures

    1. Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib [12 months]

      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

    2. Part A: Assess antitumor activity of crizotinib + AT13387 combination, circulating tumor cells (CTCs) response, progression free survival (PFS) and overall survival (OS). [12 months]

      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

    3. 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 [18 months]

      Number of patients with adverse events PFS and OS as measured in weeks Response rate as measured by RECIST 1.1 every 8 weeks

    4. 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 [18 months]

      Number of patients with adverse events PFS and OS as measured in weeks

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic-Scottsdale Scottsdale Arizona United States 85259
    2 University of California, San Diego Medical Center La Jolla California United States 92093-0698
    3 USC Norris Comprehensive Cancer Center Los Angeles California United States 90033
    4 UCLA Medical Center Los Angeles California United States 90095
    5 Sharp Clinical Oncology Research-Sharp Memorial Hospital San Diego California United States 92123
    6 Innovative Clinical Research Institute Whittier California United States 90603
    7 University of Colorado Denver Aurora Colorado United States 80045
    8 Yale University School of Medicine-Yale Cancer Center New Haven Connecticut United States 06519
    9 Christiana Hospital Newark Delaware United States 19713
    10 Florida Hospital Cancer Institute Orlando Florida United States 32804
    11 H. Lee Moffitt Cancer Center & Research Institute Tampa Florida United States 33612-9497
    12 Northwestern University The Feinberg School of Medicine Chicago Illinois United States 60611
    13 University of Chicago Chicago Illinois United States 60637
    14 Indiana University Melvin and and Bren Simon Cancer Center Indianapolis Indiana United States 46202
    15 University of Michigan Medical Center Ann Arbor Michigan United States 48109
    16 Barbara Ann Karmanos Cancer Institute Detroit Michigan United States 48201
    17 Mayo Clinic-Rochester Rochester Minnesota United States 55905
    18 Washington University School of Medicine Saint Louis Missouri United States 63110
    19 University of Nebraska Medical Center Eppley Cancer Center Omaha Nebraska United States 68198
    20 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
    21 Montefiore Medical Center Bronx New York United States 10461
    22 Columbia University Medical Center New York New York United States 10032
    23 Duke University Medical Center Durham North Carolina United States 27710
    24 Cone Health Cancer Center Greensboro North Carolina United States 27409
    25 Oncology Hematology in Cincinnati Cincinnati Ohio United States 45242
    26 University of Cincinnati Cancer Institute Cincinnati Ohio United States 45267
    27 Cleveland Clinic Cleveland Ohio United States 44195
    28 Ohio State University Medical Center Columbus Ohio United States 43210
    29 Providence Portland Medical Center Portland Oregon United States 97213
    30 The Pennsylvania State University-Penn State Hershey Pennsylvania United States 17033-0850
    31 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
    32 The West Clinic Germantown Tennessee United States 38138
    33 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    34 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    35 Virginia Cancer Specialists Fairfax Virginia United States 22031
    36 Swedish Cancer Institute Seattle Washington United States 98104
    37 University of Washington Medical Center Seattle Washington United States 98109
    38 University of Wisconsin-Carbone Cancer Center Madison Wisconsin United States 53579
    39 Atlantic Clinical Cancer Research Unit Halifax Nova Scotia Canada B3H 1V7
    40 McGill University Health Center Montreal, Quebec Canada H3A 1A1
    41 Institut Universitaire de Cardiologie et de Pneumologie De Quebec Sainte-Foy, Quebec Canada G1V 4G5
    42 Princess Margaret Hospital Toronto, Ontario Canada M5G 2M9
    43 Cancer Care Manitoba Winnipeg Canada R3E OV9
    44 Centre Hospitalier Regional Universitaire Besancon Besancon Cedex France 25030
    45 CHU de Caen-Hopital Cote de Nacre Caen France 14033
    46 Hopital Saint Antoine Creteil Cedex France 94010
    47 Centre Hospitalier de Grenoble Grenoble France 38043
    48 CHRU de Lille Lille cedex France 59037
    49 Institut Paoli-Calmettes Marseille France 13273
    50 Hopital Tenon Paris France 75020
    51 Centre Hospitalier Lyon Sud Pierre-Benite Cedex France 69495
    52 CHU Toulouse-Hopital Larrey Toulouse France 31 059
    53 Institut Gustave Roussy Villejuif France 94800
    54 Chungbuk National University Hospital Cheongju-si Korea, Republic of 362-711
    55 The Catholic University of Korea, St. Vincent's Hospital Gyeonggi-do Korea, Republic of 442-723
    56 Chonnam National University Hwasun Hospital Hwasun-gun Jeonnam Korea, Republic of 519-809
    57 National Cancer Center Korea Korea, Republic of 410-769
    58 Seoul National University Bundang Hospital Seongnam Korea, Republic of 463-707
    59 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 120-752
    60 Samsung Medical Center Seoul Korea, Republic of 135-710
    61 Asan Medical Center Seoul Korea, Republic of 138-736
    62 Hospital Germans Trias i Pujol Badalona Spain 08916
    63 Hospital Universitari Quiron Dexeus Barcelona Barcelona Spain 08028
    64 Centro Integral Oncologico Clara Campal Madrid Spain 28050
    65 Hospital Regional Universitario de Malaga Malaga Spain 29010

    Sponsors and Collaborators

    • Astex Pharmaceuticals, Inc.

    Investigators

    • Principal Investigator: Jean-Charles Soria, MD, Gustave Roussy, Cancer Campus, Grand Paris

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Astex Pharmaceuticals, Inc.
    ClinicalTrials.gov Identifier:
    NCT01712217
    Other Study ID Numbers:
    • AT13387-05
    • 2012-001575-37
    First Posted:
    Oct 23, 2012
    Last Update Posted:
    Jan 19, 2018
    Last Verified:
    Jan 1, 2018
    Keywords provided by Astex Pharmaceuticals, Inc.
    Non-small cell lung cancer
    Additional relevant MeSH terms:
    Lung Neoplasms
    Carcinoma, Non-Small-Cell Lung
    Crizotinib

    Study Results

    No Results Posted as of Jan 19, 2018