Effect of All-trans Retinoic Acid With Chemotherapy Based on Paclitaxel and Cisplatin As First-line Treatment of Patients With Advanced Non-small Cell Lung Cancer and Expression of RAR-alfa and RAR-beta as Response Biomarker

NCT01041833 | Unknown Phase 3 DMC

• 1 other identifier: CA/141/CB/563/09
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

BACKGROUND Platinum-based chemotherapy (CT) is the standard treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, the survival and response rate (RR) to CT is poor. There is great interest in new treatment strategies. One of this new strategies include the use of retinoids such as atRA. The synergistic effect of cytotoxic agents with retinoids has been demonstrated in lung cancer. At the INCan, our work group carried out a phase II study trial that included 107 patients with advanced NSCLC. They were randomized to receive atRA (20-mg/m2) or placebo combined with 80 mg/m2 of cisplatin and 175 mg/m2 of paclitaxel. The results showed a significant increase in the RR of the atRA group, reaching 55.8% ( 95% CI; 46.6-64.9%) compared with 25.4% (95% CI, 21.3-29.5%; p = 0.001) in patients who received placebo. Median Progression-free survival (PFS) in the atRA group was 8.9 months, while for those of placebo, PFS was 6.0 months (p = 0.008). There were no significant differences in the grade 3-4 side effects between groups, except for hypertriglycemia, which presented with greater frequency in the atRA group (p = 0.05). Immunohistochemical stains determine the RAR B2 expression in 6 of 60 tumor samples analyzed; however, all samples expressed RAR B2 in adjacent normal tissue. HYPOTHESIS Patients with NSCLC who receive the scheme combined with first-line CT plus 45 mg/m2 of atRA will have a greater PFS and RR to CT with an acceptable toxicological profile. OBJECTIVES

1. 1.Obtain a greater RR to CT and PFS in patients with advanced NSCLC who receive cisplatin- and paclitaxel-based CT combined with a 45-mg/m2 daily dose of atRA with an acceptable toxicological profile .
2. 2.Evaluate the benefit of RAR beta and RAR alfa expression as a response biomarker.

Conditions

Non Small Cell Lung Cancer

Keywords

All-trans retinoic acid; non-small cell lung cancer; retinoic acid receptor beta

Outcome Measures

Primary Outcomes (1)

• Obtain a greater response rate to chemotherapy, and an increase in PFS and the GS of patients with advanced-stage NSCLC who receive cisplatin- and paclitaxel-based chemotherapy and a 45-mg/m2 daily dose of atRA.

  2012

Secondary Outcomes (1)

• Demonstrate an acceptable toxicological profile of patients with advanced NSCLC who receive chemotherapy and a daily 45-mg/m2 dose of atRA.

  2013

Study Arms (2)

atRA group

EXPERIMENTAL

atRA group will receive six cycles of 80 mg/m2 of cisplatin and 175 mg/m2 of paclitaxel plus atRA 45 m2/day before one week before treatment and during all the treatment

Drug: atRA

Placebo Group

PLACEBO COMPARATOR

Placebo group will receive six cycles of 80 mg/m2 of cisplatin and 175 mg/m2 of paclitaxel plus placebo before one week before treatment and during all the treatment

Drug: Placebo

Interventions

atRA DRUG

atRA group will receive six cycles of 80 mg/m2 of cisplatin and 175 mg/m2 of paclitaxel plus atRA 45 m2/day before one week before treatment and during all the treatment

atRA group

Placebo DRUG

Placebo group will receive six cycles of 80 mg/m2 of cisplatin and 175 mg/m2 of paclitaxel plus placebo before one week before treatment and during all the treatment

Placebo Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced NSCLC (stages III B or IV according to the Tumor node metastasis \[TNM\] classification) who receive paclitaxel 175 mg/m2- and cisplatin-based palliative therapy every 3 weeks during 4 cycles,
• General status with a Karnofsky score of ≥70%,
• Eastern Cooperative Oncology Group (ECOG) ≤ 2,
• Hepatic and hematic cytology tests within normal ranges,
• Creatinine purification \> 75 ml per min,
• Those who accepted to participate in the study, and who signed the letter of informed consent.

You may not qualify if:

• Patients with comorbidity with another type of cancer who refuse to enter the protocol,
• Patients who require reduction of the chemotherapy dose due to alterations in their laboratory examinations,
• Patients with a poor general health state
• Absence of histological diagnosis, and
• Previous treatment with chemotherapy.

Sponsors & Collaborators

• National Institute of Cancerología: lead

Study Sites (1)

Department of Medical Oncology, Instituto Nacional de Cancerología

México, State of Mexico, 14080, Mexico

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Oscar Arrieta, M.D.

CONTACT

(+52) (55) 5628-0400; ogar@servidor.unam.mx

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER GOV

Study Record Dates

• First Submitted: September 7, 2009
• First Posted: January 1, 2010
• Study Start: January 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2013
• Last Updated: January 1, 2010

Record last verified: 2009-09

Locations

ME (1)