CPI-613 and Docetaxel in Treating Patients With Stage IIIB or IV Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This phase I/II trial studies the side effects and best dose of 6,8-bis(benzylthio)octanoic acid (CPI-613) when given together with docetaxel and to see how well they work in treating patients with stage IIIB or IV non-small cell lung cancer. Drugs used in chemotherapy, such as CPI-613 and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the maximum tolerate dose (MTD) of CPI-613 when used in combination with docetaxel therapy in advanced stage non-small cell lung cancer (NSCLC). (Phase1) II. To evaluate the response rate in patients receiving CPI-613 in combination with docetaxel therapy. (Phase 2) SECONDARY OBJECTIVES: I. To determine the safety of CPI-613 addition to docetaxel therapy. II. To determine the progression-free survival with CPI-613 in combination with docetaxel therapy at 27 weeks. III. To determine the median progression-free survival with CPI-613 in combination with docetaxel therapy. OUTLINE: This is a phase I, dose-escalation study of CPI-613 followed by a phase II study. Patients receive CPI-613 intravenously (IV) over 2 hours on days 1 and 3, and docetaxel IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients that achieve stable disease after 6 courses then receive CPI-613 alone on days 1and 3. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for 30 days and then periodically for 2 years.

Official Title
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A Phase I/II Open-Label Dose Escalation Trial of CPI-613 in Combination With Docetaxel Chemotherapy as a Second-Line Treatment of Non-Small-Cell Lung Cancer

Conditions
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Stage IIIB Non-Small Cell Lung Cancer AJCC v7, Stage IV Non-Small Cell Lung Cancer AJCC v7

Intervention / Treatment
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* Drug: 6,8-Bis(benzylthio)octanoic Acid
* Drug: Docetaxel
* Other: Pharmacological Study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically or cytologically confirmed stage IIIB or IV NSCLC with radiographic proof of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 Life expectancy of >= 3 months Patients must have received previous systemic therapy to include: a regimen of chemotherapy, immunotherapy including anti-PDL or anti-PD-L1 therapies, combined chemotherapy and immunotherapy, provided treatment was discontinued >= 2 weeks prior to initiation of treatment on the present protocol Absolute neutrophil count >= 1,500/uL Platelets >= 100,000/uL Total bilirubin within normal institutional limits Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) within institutional upper limit of normal International normalized ratio (INR) =< 1.5 x upper limit of normal (ULN) Prothrombin time (PT) =< 1.5 x ULN Activated partial thromboplastin time (aPTT) =< 1.5 x ULN or within therapeutic range if receiving anticoagulant therapy OR Creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study through 30 days after the last dose of study medication; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document (either directly or via a legally authorized representative) Exclusion Criteria: Patients who have had immunotherapy or tyrosine kinase inhibitor (TKI) therapy within two weeks prior to entering the study Radiotherapy or prior systemic chemotherapy within 2 weeks Patients who have been treated with more than one chemotherapy regimen, immunotherapy regimen or chemotherapy/immunotherapy regimen for metastatic non-small cell lung cancer Adverse events resulting from previous therapies have not recovered to grade 1 or less Patients may not be receiving any other investigational agents Patients with untreated, symptomatic brain metastases should be excluded from this clinical trial (patients with asymptomatic brain metastases amenable to treatment with Gamma Knife radiosurgery [GKRS] are eligible and may receive GKRS while on protocol) Lactating females Patients with EGFR, ALK or ROS-1 mutations who are eligible for treatment with a TKI and who have not received such treatment History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPI-613 or docetaxel Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with CPI-613 Any condition that may, in the opinion of the investigator, compromise the safety of the patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (CPI-613, docetaxel)<br>Patients receive CPI-613 IV over 2 hours on days 1 and 3, and docetaxel IV on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients that achieve stable disease after 6 courses then receive CPI-613 alone on days 1and 3. Courses repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. | Drug: 6,8-Bis(benzylthio)octanoic Acid<br>* Given IV<br>* Other names: CPI-613;Drug: Docetaxel<br>* Given IV<br>* Other names: Taxotere Injection Concentrate;Other: Pharmacological Study<br>* Correlative studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase II dose of 6,8-bis(benzylthio)octanoic acid (CPI-613) when administered in combination with a standard dose of docetaxel (Phase 1) |  | Up to 18 weeks | 
| Response rate defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 2) | Will estimate the proportion of patients with a response (complete response + partial response) and calculate a 95% confidence interval for this measure. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median progression-free survival (PFS) | Will estimate the median PFS using standard survival methods (Kaplan Meier). | From the start of treatment to the time of progression or death, assessed up to 2 years | 
| Number and degree of adverse events under the experimental therapy regimens graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 | Will be estimated along with 95% confidence intervals for each adverse event. These estimates will be compared (not using specific statistical tests, but descriptively) to those reported in patients treated with docetaxel. | Up to 30 days after the last study drug is administered | 
| Overall survival (OS) |  | From the start of treatment to date of death, assessed up to 2 years | 
| Progression-free survival (PFS) |  | From the start of treatment to the time of progression or death, assessed at 27 weeks |