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

October 11, 2012
September 26, 2014
October 2012
June 2015   (final data collection date for primary outcome measure)
  • 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
  • Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. [ Time Frame: 15 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 + AT133187. [ Time Frame: 7 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: 8 months ] [ Designated as safety issue: No ]
    - Change in tumor measurements by RECIST 1.1 every 8 weeks
Complete list of historical versions of study NCT01712217 on ClinicalTrials.gov Archive Site
  • 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
  • Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib [ Time Frame: 15 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: 15 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: 7 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: 8 months ] [ Designated as safety issue: Yes ]
    • Number of patients with adverse events
    • PFS and OS as measured in weeks
Not Provided
Not Provided
 
A Study of AT13387 in Patients With Non-Small Cell Lung Cancer (NSCLC) Alone and in Combination With Crizotinib
A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Non-small Cell Lung Cancer(NSCLC)
  • Drug: AT13387
    HSP90 inhibitor
  • Drug: Crizotinib
    ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
    Other Name: Xalkori
  • 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.
    Interventions:
    • Drug: AT13387
    • Drug: Crizotinib
  • 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.
    Interventions:
    • Drug: AT13387
    • Drug: Crizotinib
  • 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.
    Interventions:
    • Drug: AT13387
    • Drug: Crizotinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
228
February 2016
June 2015   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Medpace Recruitment, Center 1-866-872-2349 recruitment@medpace.com
Korea, Republic of,   Canada,   United States,   France,   Spain
 
NCT01712217
AT13387-05, 2012-001575-37
No
Astex Pharmaceuticals
Astex Pharmaceuticals
Not Provided
Principal Investigator: Jean-Charles Soria, MD Gustave Roussy, Cancer Campus, Grand Paris
Astex Pharmaceuticals
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP