Effect of All-trans Retinoic Acid With Chemotherapy Based in Paclitaxel and Cisplatin as First Line Treatment of Patients With Advanced Non-small Cell Lung Cancer

Condition(s) targeted: Non-Small-Cell Lung Carcinoma

Intervention: ATRA (Drug); PLACEBO (Other)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Cancerología

Official(s) and/or principal investigator(s):
Oscar Arrieta, M.D., Principal Investigator, Affiliation: National Institute of Cancerología

Purpose: This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel plus All-trans retinoic acid (ATRA) increases Response rate (RR) and Progression-free survival (PFS) in patients with advanced Non-small cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of Retinoic acid receptor beta 2 (RAR-beta2) as a response biomarker. Patients and Methods: Patients with stage IIIB and IV NSCLC were included to receive Paclitaxel and Cisplatin (PC). Patients were randomized to receive ATRA 20 mg/m2/day (RA/PC) or placebo (P/PC) 1 week prior to treatment until completing two cycles. RAR-beta2 expression was analyzed by Immunohistochemistry (IHC) and RT-PCR in tumor and adjacent lung tissue.

Official title: Randomized Phase II Trial: Effect of All-trans Retinoic Acid With Chemotherapy Based in Paclitaxel and Cisplatin as First Line Treatment of Patients With Advanced Non-small Cell Lung Cancer

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

Primary outcome: The primary end-point was Response rate (RR) and Progression-free survival (PFS), as well as identifying whether expression of RAR-beta2 is a response biomarker.

Secondary outcome: Evaluate the efficiency and safety of low doses of ATRA in patients with advanced NSCLC who receive first-line CT.

Detailed description: Purpose: This randomized phase II trial evaluated whether the combination of cisplatin and paclitaxel plus All-trans retinoic acid (ATRA) increases Response rate (RR) and Progression-free survival (PFS) in patients with advanced Non-small cell lung cancer (NSCLC) with an acceptable toxicity profile and its association with the expression of Retinoic acid receptor beta 2 (RAR-beta2 ) as a response biomarker. Patients and Methods: Patients with stage IIIB and IV NSCLC were included to receive Paclitaxel and Cisplatin (PC). Patients were randomized to receive ATRA 20 mg/m2/day (RA/PC) or placebo (P/PC) 1 week prior to treatment until completing two cycles. RAR-beta2 expression was analyzed by Immunohistochemistry (IHC) and RT-PCR in tumor and adjacent lung tissue.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Stage III B and IV NSCLC

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- No prior cytotoxic chemotherapy for NSCLC

- Age ≥18 years, adequate laboratory measurements

- Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)

- Life expectancy of >12 weeks.

Exclusion Criteria:

- Patients who had received prior chemotherapy

- Patients with other comorbid conditions

National Institute of Cancerología, Mexico City 14080, Mexico

Starting date: September 2007
Last updated: January 12, 2010