Gossypol Combined With Docetaxel and Cisplatin Scheme in Advanced Non Small-cell Lung Cancers With APE1 High Expression

Study Overview
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Brief Summary
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The investigators' experimental study found that gossypol was the natural inhibitor of apyrimidinic endonuclease 1 (APE1) and clinical study observed that high expression of APE1 was relative to the platinum-resistance in non-small cell lung cancer. Thus the purpose of this study is to find out whether gossypol can improve the sensitivity of cisplatin-based chemotherapy in the non-small cell lung cancer with apurinic apyrimidinic endonuclease 1 (APE1) high expression

Official Title
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A Randomized, Double Blind, Placebo-controlled Multiple-center Phase III Trial of Gossypol Combined With Docetaxel and Cisplatin Scheme in Advanced Non Small-cell Lung Cancers With APE1 High Expression

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: Gossypol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic diagnosis of NSCLC, Stage IIIB/IV. Males or females between 18 Years to 75 Years. No prior cisplatin-based chemotherapy, if the surgery or radiotherapy has been administered, the interval is at least above four weeks. The interval for targeted therapy such as EGFR TKI is above 2 weeks. Performance status of 0, 1 on the ECOG criteria. Expected survival is above three months. At least one unidimensional measurable lesion meeting Response Evaluation Criteria in Solid Tumors (RECIST. 2000). Patients can have the brain / meningeal metastasis history, but the metastasis must be treated by operation or radiotherapy), and clinically stable for at least 2 months. Adequate hematologic (neutrophil count >= 1,500/uL, platelets >= 100,000/uL), hepatic (transaminase =< upper normal limit(UNL)x2.5, bilirubin level =< UNLx1.5), and renal (creatinine =< UNL) function. Patient compliance that allow adequate follow-up. Informed consent from patient or patient's relative. APE1 IHC (++ or +++). If female: childbearing potential either terminated by surgery, radiation, or menopause, or attenuated by use of an approved contraceptive method (intrauterine device [IUD], birth control pills, or barrier device) during and for 2 months after trial. If male, use of an approved contraceptive method during the study and 2 months afterwards. Females with childbearing potential must have a urine negative HCG test within 7 days prior to the study enrollment. No concomitant prescriptions including cyclosporin A, valproic acid, phenobarbital, phenytoin, ketoconazole. Exclusion Criteria: Inability to comply with protocol or study procedures. Medically uncontrolled serious heart, lung, neurological, psychological, metabolic disease. Second primary malignancy that is clinically detectable at the time of consideration for study enrollment. Pregnant or breast-feeding. Enrollment in other study within 30 days. Brain metastasis with symptoms. Hypokalemic periodic paralysis history.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Docetaxel 75mg/m2/iv over 90min and cisplatin 75mg/m2/iv over 90min on day 1. Gossypol 20mg from day 1 to day 14. repeat Q 3weeks. Four cycles. | Drug: Gossypol<br> <br> |
| Placebo Comparator: Arm B<br>Docetaxel 75mg/m2/iv over 90min and cisplatin 75mg/m2/iv over 90min on day 1. Placebo from day 1 to day 14. repeat Q 3weeks. Four cycles. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | the first day of treatment to the date that disease progression is reported; assesed up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | the first day of treatment to death or last survival confirm date; assesed up to 4 years | 
| Tumor response rate | The ratio between the number of responders and number of patients assessable for tumor response | Up to 4 years | 
| Toxicity | Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. | the first date of treatment to 30 days after the last dose of study drug | 
| Quality of life |  | the day before every cycle of chemotherapy; 30 days after the last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC; Gossypol; APE1; Chemotherapy