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

Non-small Cell Lung Cancer Clinical Trial

— GTCA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01977209
• Other study ID #: GTCA
• Status: Recruiting
• Phase: Phase 3
• First received: October 19, 2013
• Last updated: October 30, 2013
• Start date: September 2013
• Est. completion date: September 2016

Study information

• Verified date: October 2013
• Source: Third Military Medical University
• Contact: Dong Wang, PH.D.
• Phone: 86-23-68757151
• Email: dongwang64[@]hotmail.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 204
• Est. completion date: September 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• Gossypol

• Placebo

Locations

Country	Name	City	State
China	Chongqing Zhongshan Hospital	Chongqing	Chongqing
China	Daping Hospital, Third Military Medical University	Chongqing	Chongqing
China	Fuling Central Hospital	Chongqing	Chongqing
China	Jiangjin Central Hospital	Chongqing	Chongqing
China	The Second Affiliated Hospital of Medical University Of Chongqing	Chongqing	Chongqing
China	Three Gorges Central Hospital	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Third Military Medical University

Country where clinical trial is conducted

China, 

References & Publications (6)

Bepler G, Williams C, Schell MJ, Chen W, Zheng Z, Simon G, Gadgeel S, Zhao X, Schreiber F, Brahmer J, Chiappori A, Tanvetyanon T, Pinder-Schenck M, Gray J, Haura E, Antonia S, Fischer JR. Randomized international phase III trial of ERCC1 and RRM1 expression-based chemotherapy versus gemcitabine/carboplatin in advanced non-small-cell lung cancer. J Clin Oncol. 2013 Jul 1;31(19):2404-12. doi: 10.1200/JCO.2012.46.9783. Epub 2013 May 20. — View Citation

Kelley MR, Georgiadis MM, Fishel ML. APE1/Ref-1 role in redox signaling: translational applications of targeting the redox function of the DNA repair/redox protein APE1/Ref-1. Curr Mol Pharmacol. 2012 Jan;5(1):36-53. Review. — View Citation

Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC; IALT Bio Investigators. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006 Sep 7;355(10):983-91. — View Citation

Ready N, Karaseva NA, Orlov SV, Luft AV, Popovych O, Holmlund JT, Wood BA, Leopold L. Double-blind, placebo-controlled, randomized phase 2 study of the proapoptotic agent AT-101 plus docetaxel, in second-line non-small cell lung cancer. J Thorac Oncol. 2011 Apr;6(4):781-5. doi: 10.1097/JTO.0b013e31820a0ea6. — View Citation

Sonpavde G, Matveev V, Burke JM, Caton JR, Fleming MT, Hutson TE, Galsky MD, Berry WR, Karlov P, Holmlund JT, Wood BA, Brookes M, Leopold L. Randomized phase II trial of docetaxel plus prednisone in combination with placebo or AT-101, an oral small molecule Bcl-2 family antagonist, as first-line therapy for metastatic castration-resistant prostate cancer. Ann Oncol. 2012 Jul;23(7):1803-8. doi: 10.1093/annonc/mdr555. Epub 2011 Nov 23. — View Citation

Wang D, Xiang DB, Yang XQ, Chen LS, Li MX, Zhong ZY, Zhang YS. APE1 overexpression is associated with cisplatin resistance in non-small cell lung cancer and targeted inhibition of APE1 enhances the activity of cisplatin in A549 cells. Lung Cancer. 2009 Dec;66(3):298-304. doi: 10.1016/j.lungcan.2009.02.019. Epub 2009 Mar 25. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival		the first day of treatment to the date that disease progression is reported; assesed up to 4 years	No
Secondary	Overall survival		the first day of treatment to death or last survival confirm date; assesed up to 4 years	No
Secondary	Tumor response rate	The ratio between the number of responders and number of patients assessable for tumor response	Up to 4 years	No
Secondary	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	Yes
Secondary	Quality of life		the day before every cycle of chemotherapy; 30 days after the last dose of study drug	No