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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01041833
Recruitment Status : Unknown
Verified September 2009 by National Institute of Cancerología.
Recruitment status was:  Not yet recruiting
First Posted : January 1, 2010
Last Update Posted : January 1, 2010
Sponsor:
Information provided by:

Study Description
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. 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 or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Drug: atRA Drug: Placebo Phase 3

  Show Detailed Description

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, 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
Study Start Date : January 2010
Estimated Primary Completion Date : September 2011
Estimated Study Completion Date : September 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: atRA group
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
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 Comparator: Placebo Group
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
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


Outcome Measures

Primary Outcome Measures :
  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. [ Time Frame: 2012 ]

Secondary Outcome Measures :
  1. 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 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01041833


Contacts
Contact: Oscar Arrieta, M.D. (+52) (55) 5628-0400 ext 832 ogar@servidor.unam.mx

Locations
Mexico
Department of Medical Oncology, Instituto Nacional de Cancerología Not yet recruiting
Mexico, Mexico, 14080
Contact: Oscar Arrieta, M.D.    (+52) (55) 5628-0400 ext 832    ogar@servidor.unam.mx   
Contact: Oscar Arrieta    (+52) (55) 5628-0400 ext 832    ogar@servidor.unam.mx   
Sponsors and Collaborators
National Institute of Cancerología
More Information

Responsible Party: Oscar Arrieta, M.D., Department of Medical Oncology, Instituto Nacional de Cancerología
ClinicalTrials.gov Identifier: NCT01041833     History of Changes
Other Study ID Numbers: CA/141/CB/563/09
First Posted: January 1, 2010    Key Record Dates
Last Update Posted: January 1, 2010
Last Verified: September 2009

Keywords provided by National Institute of Cancerología:
All-trans retinoic acid
non-small cell lung cancer
retinoic acid receptor beta

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
Paclitaxel
Albumin-Bound Paclitaxel
Cisplatin
Tretinoin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Keratolytic Agents
Dermatologic Agents