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

Third Military Medical University

Status and phase: Unknown; Phase 3

Conditions: Non-small Cell Lung Cancer

Treatments: Drug: Placebo; Drug: Gossypol

Study type: Interventional

Funder types: Other

Identifiers

NCT01977209

GTCA

Details and patient eligibility

About

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

Enrollment: 204 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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204 participants in 2 patient groups, including a placebo group

Arm A

Experimental group

Description:

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.

Treatment:

Drug: Gossypol

Arm B

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo