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Completed

NCT Number: NCT01712217

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

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.

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Key information

Conditions

Non-small Cell Lung Cancer(NSCLC) Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Atlantic Clinical Cancer Research Unit, Halifax, Nova Scotia, Canada

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • Prior anti-cancer treatment with any HSP90 inhibitor
  • Have received chemotherapy, radiation therapy or other anticancer treatment other than crizotinib within 3 weeks prior to the first dose of study drug
  • 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
  • Abnormal heart function
  • Presence of a life-threatening illness, medical condition, organ system dysfunction, or other factors
  • Hypersensitivity of AT13387 or other components of the drug product
  • Treatment with an investigational drug within 3 weeks prior to the first dose of study drug
  • Severe systemic diseases or active uncontrolled infections
  • Known history of human immunodeficiency virus (HIV) or seropositive test for hepatitis C virus or hepatitis B virus

Treatment and study plan

AT13387

Drug

HSP90 inhibitor

Crizotinib

Drug

ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor

Other names: Xalkori

Primary outcomes

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

    Time frame: 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.

    Time frame: 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.

    Time frame: 18 months

    • Change in tumor measurements by RECIST 1.1 every 8 weeks

Secondary outcomes

  1. Part A: Pharmacokinetics of combination treatment with AT13387 and crizotinib

    Time frame: 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).

    Time frame: 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

    Time frame: 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

    Time frame: 18 months

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

Sponsors and collaborators

Lead sponsor

Astex Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Study of HSP90 Inhibitor AT13387 Alone and in Combination With Crizotinib in the Treatment of Non-small Cell Lung Cancer (NSCLC)

Important dates

Study start
2012
Primary completion
2016
Study completion
2017
First posted
Oct 23, 2012
Registry last updated
Aug 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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