Non-small Cell Lung Cancer(NSCLC)
Conditions
Keywords
Non-small cell lung cancer
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.
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.
Interventions
DRUGAT13387
HSP90 inhibitor
DRUGCrizotinib
ALK (anaplastic lymphoma kinase) and ROS1 (c-ros oncogene1, receptor tyrosine kinase) inhibitor
Sponsors
Astex Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: The incidence of dose limiting toxicities when AT13387 is administered in combination with crizotinib. | 12 months | \- 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. | 18 months | \- 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. | 18 months | \- Change in tumor measurements by RECIST 1.1 every 8 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Canada, France, South Korea, Spain, United States
Outcome results
None listed