Individualized Chemotherapy Based on BRCA1 and RRM1 mRNA for Advanced Non-small Cell Lung Cancer (NSCLC) (BRAVO)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Caicun Zhou, Tongji University
ClinicalTrials.gov Identifier:
NCT01424709
First received: May 9, 2011
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

Gemcitabine, docetaxel, CPT-11 and cisplatin are effective in 1st line treatment of advanced non-small cell lung cancer (NSCLC). Platinum-based doublets including gemcitabine, docetaxel or CPT-11 are standard 1st regimens. BRCA1 and RRM1 expression levels are reported to be associated with sensitivity of the tumor cells to cytotoxic agents. Some Phase II or III trials did prove feasibility of customized chemotherapy based upon expression levels of one or two biomarkers in the NSCLC patients. The investigators think customized chemotherapy may further improve efficacy of chemotherapy in advanced NSCLC. But there is no randomised trial to compare efficacy of standard chemotherapy with individualized chemotherapy in this setting. So, the investigators plan to initiate this phase II trial to compare efficacy between standard chemotherapy of gemcitabine/cisplatin versus customized chemotherapy in chemonaive NSCLC patients.


Condition Intervention Phase
Non-small Cell Lung Cancer
Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin
Drug: gemcitabine/cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Individualized 1st Line Chemotherapy Based on BRCA1 and RRM1 mRNA Expression Levels for Advanced Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Tongji University:

Primary Outcome Measures:
  • Overall response rate [ Time Frame: tumor assessment 6-8 weeks after the initiation of chemotherapy ] [ Designated as safety issue: No ]
    to evaluate ORR during 6-8 weeks after all cycles complete


Secondary Outcome Measures:
  • Progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    PFS is evaluated in the 24th month since the treatment began

  • duration of response [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    evaluated in the 24th month since the treatment began

  • overall survival [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    evaluated in the 24th month since the treatment began

  • safety [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    evaluated in the 24th month since the treatment began

  • Quality Of Life [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    evaluated in the 24th month since the treatment began


Estimated Enrollment: 120
Study Start Date: December 2010
Estimated Study Completion Date: December 2014
Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
Based on expression levels of RRM1 and BRCA1 mRNA,one of the four regimens will be given to each patient: Gemcitabine/cisplatin, Docetaxel/gemcitabine, CPT-11/Cisplatin, docetaxel monotherapy. The chemotherapy will be repeated every 3 week. Dose reduction or interruption for toxicity could take place at any time.
Drug: Gemcitabine, Docetaxel, CPT-11,Cisplatin
Based on expression levels of RRM1 and BRCA1 mRNA,one of the four regimens will be given to each patient: Gemcitabine/cisplatin, Docetaxel/gemcitabine, CPT-11/Cisplatin, docetaxel monotherapy. The chemotherapy will be repeated every 3 week. Dose reduction or interruption for toxicity could take place at any time.
Other Names:
  • gemcitabine:Gemzar
  • Docetaxel:Taxotere
  • CPT-11:Irinotecan
Active Comparator: Arm 2
gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.
Drug: gemcitabine/cisplatin
gemcitabine/cisplatin up to 6 cycles or disease progression or intolerable toxicity.
Other Name: gemcitabine:Gemzar

Detailed Description:

Primary end point:ORR Secondary end point:PFS,OS,safety,QOL,etc.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent,
  2. Histologically confirmed stage M1a or M1b NSCLC,
  3. Aged over 18 years old,
  4. Measurable disease,
  5. Life expectancy of at least 12 weeks,
  6. No prior chemotherapy or target therapy,
  7. No brain metastases or spinal cord compression,
  8. Less than 10% body weight loss,
  9. ECOG performance status 0-2,
  10. Adequate vital organ function (haematological, renal, hepatic, etc).
  11. Enough tissue for detection of BRCA1 and RRM1 expression.

Exclusion Criteria:

  1. Prior systemic cytotoxic chemotherapy or EGFR TKI therapy,
  2. Positive pregnancy test,
  3. Another active malignancy, other than superficial basal cell and squamous cell or carcinoma in situ of the cervix, within the last 5 years,
  4. Patients with brain metastases or spinal cord compression,
  5. Allergy to gemcitabine, cisplatin, docetaxel, CPT-11,
  6. Any unstable systemic disease including active infection,
  7. No enough tissue for detection of BRCA1 and RRM1
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01424709

Locations
China
Medical Department, Shanghai Pulmonary Hospital
Shanghai, China, 200433
Sponsors and Collaborators
Tongji University
Investigators
Principal Investigator: Caicun Zhou, Ph.D Tongji University Affiliated Shanghai Pulmonary Hospital
  More Information

No publications provided

Responsible Party: Caicun Zhou, Tonji University Affiliated Shanghai Pulmonary Hospital, Tongji University
ClinicalTrials.gov Identifier: NCT01424709     History of Changes
Other Study ID Numbers: BRAVO study
Study First Received: May 9, 2011
Last Updated: September 23, 2014
Health Authority: China: Food and Drug Administration

Keywords provided by Tongji University:
Chemotherapy
Individual therapy
RRM1
BRCA1

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Docetaxel
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators

ClinicalTrials.gov processed this record on October 01, 2014