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

Primary Purpose

Non-small Cell Lung Cancer

Status
Unknown status
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Gossypol
Placebo
Sponsored by
Third Military Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer focused on measuring NSCLC; Gossypol; APE1; Chemotherapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Daping Hospital, Third Military Medical UniversityRecruiting
  • Chongqing Zhongshan HospitalRecruiting
  • Fuling Central HospitalRecruiting
  • Jiangjin Central HospitalRecruiting
  • The Second Affiliated Hospital of Medical University Of ChongqingRecruiting
  • Three Gorges Central HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm A

Arm B

Arm 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.

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.

Outcomes

Primary Outcome Measures

Progression-free survival

Secondary Outcome Measures

Overall survival
Tumor response rate
The ratio between the number of responders and number of patients assessable for tumor response
Toxicity
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Quality of life

Full Information

First Posted
October 19, 2013
Last Updated
October 30, 2013
Sponsor
Third Military Medical University
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1. Study Identification

Unique Protocol Identification Number
NCT01977209
Brief Title
Gossypol Combined With Docetaxel and Cisplatin Scheme in Advanced Non Small-cell Lung Cancers With APE1 High Expression
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Unknown status
Study Start Date
September 2013 (undefined)
Primary Completion Date
February 2016 (Anticipated)
Study Completion Date
September 2016 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Third Military Medical University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Cancer
Keywords
NSCLC; Gossypol; APE1; Chemotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
204 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A
Arm Type
Experimental
Arm 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.
Arm Title
Arm B
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Gossypol
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Progression-free survival
Time Frame
the first day of treatment to the date that disease progression is reported; assesed up to 4 years
Secondary Outcome Measure Information:
Title
Overall survival
Time Frame
the first day of treatment to death or last survival confirm date; assesed up to 4 years
Title
Tumor response rate
Description
The ratio between the number of responders and number of patients assessable for tumor response
Time Frame
Up to 4 years
Title
Toxicity
Description
Toxicity as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame
the first date of treatment to 30 days after the last dose of study drug
Title
Quality of life
Time Frame
the day before every cycle of chemotherapy; 30 days after the last dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dong Wang, PH.D.
Phone
86-23-68757151
Email
dongwang64@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dong Wang, PH.D.
Organizational Affiliation
Cancer Center, Daping Hospital, Third Military Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Daping Hospital, Third Military Medical University
City
Chongqing
State/Province
Chongqing
ZIP/Postal Code
400042
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dong Wang, PH.D.
Phone
86-23-68757151
Email
dongwang64@hotmail.com
First Name & Middle Initial & Last Name & Degree
Dong Wang, PH.D.
Facility Name
Chongqing Zhongshan Hospital
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhixiang Yang, M.D.
Phone
13032372491
First Name & Middle Initial & Last Name & Degree
Zhixiang Yang
Facility Name
Fuling Central Hospital
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qi Zhou, M.D.
Phone
86-23-7222676
First Name & Middle Initial & Last Name & Degree
Qi Zhou, M.D.
Facility Name
Jiangjin Central Hospital
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Debing Xiang, M.D.
Phone
86-13320336639
First Name & Middle Initial & Last Name & Degree
Debing Xiang, M.D.
Facility Name
The Second Affiliated Hospital of Medical University Of Chongqing
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xianquan Zhang, M.D.
Phone
86-23-63693000
First Name & Middle Initial & Last Name & Degree
Xianquan Zhang, M.D.
Facility Name
Three Gorges Central Hospital
City
Chongqing
State/Province
Chongqing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Biyong Ren
Phone
13896327099
First Name & Middle Initial & Last Name & Degree
Biyong Ren, M.D.

12. IPD Sharing Statement

Citations:
PubMed Identifier
16957145
Citation
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Results Reference
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PubMed Identifier
22122463
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. doi: 10.2174/1874467211205010036.
Results Reference
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PubMed Identifier
19324449
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.
Results Reference
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PubMed Identifier
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Citation
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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.
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Citation
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.
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Gossypol Combined With Docetaxel and Cisplatin Scheme in Advanced Non Small-cell Lung Cancers With APE1 High Expression

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