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

This study is not yet open for participant recruitment.
Verified on September 2009 by National Institute of Cancerología

First Received on September 7, 2009.  
Last Updated on December 31, 2009  
History of Changes
This Clinical Trial Sponsored By: National Institute of Cancerología
Information provided by: National Institute of Cancerología
ClinicalTrials.gov Identifier: NCT01041833
 

Purpose for Clinical Trial

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. 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. Evaluate the benefit of RAR beta and RAR alfa expression as a response biomarker.

METHODS Three hundred and thirty patients with advanced NSCLC will be included to receive Paclitaxel 175 mg/m2 and Cisplatin 80 mg/m2 (PC) every 21 days for 6 cycles. Patients will be randomized to receive ATRA 45 mg2/day or placebo 1 week before treatment until completing six cycles. Imaging studies will be performed prior and after two cycles of CT to assess response. RAR beta and RAR alfa expression will be analyzed by immunohistochemistry in lung tumoral tissue and in the adjacent lung tissue.

Condition Study Intervention Clinical Trial Phase
Non Small Cell Lung Cancer Drug: atRA
Drug: Placebo
Phase III

Study Type: Study Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Study Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Randomized Phase III Trial: 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 Biomarkers

Resource links provided by NLM:

MedlinePlus related topics:
Cancer
Lung Cancer
Drug Information available for:
Cisplatin
Paclitaxel
Tretinoin

U.S. FDA Resources

Further study details as provided by National Institute of Cancerología:

Primary Outcome Measures For Clinical Trial:

  • 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. [ Time Frame: 2012 ] [ Designated as safety issue: No ]

Secondary Outcome Measures For Clinical Trial:

  • Demonstrate an acceptable toxicological profile of patients with advanced NSCLC who receive chemotherapy and a daily 45-mg/m2 dose of atRA. [ Time Frame: 2013 ] [ Designated as safety issue: No ]

Estimated Enrollment: 230
Study Start Date: January 2010
Estimated Study Completion Date: September 2013
Estimated Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)

Arms

Assigned Study Interventions

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
Study Intervention: Drug: atRA
Drug: atRA

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
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
Study Intervention: Drug: Placebo
Drug: Placebo

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

 
Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041833

Leave a Reply

You can use these HTML tags

<a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

  

  

  

16 − four =