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Trial record 1 of 1 for:    NCT01712217
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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

  Show 65 Study Locations
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 November 20, 2014