Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma

NCT ID: NCT00617656

Last Updated: 2024-01-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 382 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2015-04-30

Brief Summary

Primary objective:

· Progression free survival.

Secondary objectives:

• Assess Overall survival of both treatment groups.
• Assess Tumor response rate using RECIST criteria
• Assess Toxicity profile of patients enrolled in the study.
• Exploratory evaluation of potential genetic markers of response or resistance to chemotherapy.

Detailed Description

Study population:

Patients with advanced non-small-cell lung cancer who have not received treatment for the disease at this stage and who have a good performance status (ECOG 0-1) and measurable disease (at least one target lesion according to RECIST criteria).

Duration of treatment:

Six chemotherapy cycles will be given. The duration of every cycle will be 21 days. If the treatment is beneficial, it may be prolonged to a total of 8 cycles at the discretion of the investigator.

Calendar and planned finalization date:

The approximate duration of the study is 3 years of recruitment followed by 1 year of follow-up.

Conditions

Non Small Cell Lung Cancer; BRCA1 Mutation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A: Control

Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6

Group Type: ACTIVE_COMPARATOR

Cisplatin, Docetaxel

Intervention Type: DRUG

Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6

B1: Experimental group B1

Low RAP expression and any levels of BRCA1 expression: Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6

Group Type: EXPERIMENTAL

Gemcitabine, Cisplatin

Intervention Type: DRUG

Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6

B2: Experimental group B2

Intermediate or high RAP expression and low or intermediate BRCA1 expression: Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6

Group Type: EXPERIMENTAL

Docetaxel, Cisplatin

Intervention Type: DRUG

Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6

B3: Experimental group B3

Intermediate or high RAP expression and high BRCA1 expression: Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6

Interventions

Cisplatin, Docetaxel

Docetaxel 75 mg/m2 and cisplatin 75 mg/m2, both on day 1, every 21 days. Total number of cycles: 6

Intervention Type: DRUG

Gemcitabine, Cisplatin

Gemcitabine 1250 mg/m2, days 1 and 8, and Cisplatin 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6

Intervention Type: DRUG

Docetaxel, Cisplatin

Docetaxel 75 mg/m2 and Cisplatin 75 mg/m2, both administered on day 1, every 21 days. Total number of cycles: 6

Intervention Type: DRUG

Docetaxel

Docetaxel 75 mg/m2, day 1. 21-day cycles. Total number of cycles: 6

Intervention Type: DRUG

Other Intervention Names

Platinol; Taxotere; Gemzar; Platinol; Taxotere; Platinol; Taxotere

Eligibility Criteria

Inclusion Criteria

1. Patients age 18 years or more.

2. Histologically confirmed diagnosis of non-small-cell lung carcinoma.

3. Only patients with advanced disease defined as stage IV or IIIB with or without pleural effusion will be included. In the event of IIIB disease without pleural effusion those patients, who for some reason (respiratory disease, large radiation volume...) may not be candidates to have chemotherapy and radiotherapy treatment and may only be treated with chemotherapy, will be considered.

4. Tumor specimen available (according to the criterion of the specimen-processing laboratory) for the analysis of RAP80 and BRCA1 expression in mRNA.

5. A measurable lesion, as defined by RECIST criteria.

6. Karnofsky score 80% or more (ECOG < 2).

7. No previous treatment with chemotherapy or other agents for disseminated disease. Chemotherapy is allowed if the patient's initial diagnosis is limited disease and the patient has received adjuvant or neoadjuvant treatment, as long as a minimum of 6 months has passed since the end of the adjuvant and/or neo-adjuvant chemotherapy.

8. Patients with cerebral disease may be included without any time limitations after holocranial irradiation or complementary antiedema treatment, as long as there is correct control of the clinical symptoms arising from the brain disease or is symptomatic.

9. Patients with the following hematologic values:

ANC ≥ 1.5 x 109/L Hb ≥ 10 g/dl Platelets ≥ 100 x 109/L

10. Patients with the following biochemical values:

Bilirubin ≤ 1.5 mg/dL AST and ALT < 1.5 upper limit of normality Creatinine clearance ≥ 60 ml/min.

11. Patients of childbearing age of either sex must use effective contraceptive methods (barrier methods or other birth control methods) before entering the study and while participating in the study.

12. Patients should sign an informed consent form before inclusion in the study that specifies that the clinical trial treatment entails consent for the analysis of biological specimens of tumor and blood.

13. Patients must be available for clinical follow-up.

Exclusion Criteria

1. Previous chemotherapy treatment, except the supposition reflected in inclusion criterion 7.

2. Patients diagnosed of another neoplasm, with the exception of cervical carcinoma in situ, treated squamous cell carcinomas or superficial bladder tumors (Ta and TIS), or other malignant tumors that have received curative treatment within the last 5 years before inclusion in the study.

3. Patients with serious active bacterial or fungal infective processes from a clinical vantage point (= grade 2 of NCI-CTC, Version 3).

4. Patients who have received an investigational medicinal product in the 21 days before inclusion in the study.

5. Patients with HIV infection, HCV infection, coronary artery disease or uncontrolled arrhythmia, uncontrolled cerebrovascular disease, or other clinical conditions that, in the judgment of the investigator, contraindicate the patient's participation in the study.

6. Patients who are pregnant or breastfeeding. Women of childbearing age must have a negative pregnancy test performed within 7 days before the onset of treatment.

7. Substance abuse and clinical, psychological or social conditions that can undermine the validity of the informed consent or protocol compliance.

8. Patients who present any contraindication or suspected allergy to the products under investigation in the study

9. Impossibility to comply with chemotherapy treatment due to cultural or geographic circumstances.

10. Significant weight loss (= 10% of body weight) in the 6 weeks before inclusion in the study.

11. Any condition that is unstable or could endanger the patient's safety and/or the patient's compliance with the study.

12. Contraindication for steroid use.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Spanish Lung Cancer Group

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Rafel Rossell, MD

Role: PRINCIPAL_INVESTIGATOR

Principal Investigator of Fundación Grupo Español de Cáncer de Pulmón

Locations

H. Virgen de los Lirios

Alcoy, Alicante, Spain

H. Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital D'Althaia

Manresa, Barcelona, Spain

Hospital de Mataró

Mataró, Barcelona, Spain

Hospital de Cruces

Barakaldo, Bizkaia, Spain

Hospital Reina Sofía

Córdoba, Córdoba, Spain

F.H.Alcorcón

Alcorcón, Madrid, Spain

H. Severo Ochoa

Leganés, Madrid, Spain

Clinica Quiron

Pozuelo de Alarcón, Madrid, Spain

Hospital Universitario Quirón Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital de Basurto

Bilbao, Vizcaya, Spain

Hospital Ernest Lluch

Calatayud, Zaragoza, Spain

H. Juan Canalejo

A Coruña, , Spain

H. Santiago de Compostela

A Coruña, , Spain

H. Gral. Alicante

Alicante, , Spain

H. Torrecárdenas

Almería, , Spain

Hospital Torrecárdenas

Almería, , Spain

H. Clinic i Provincial

Barcelona, , Spain

H. Universitario Quirón Dexeus

Barcelona, , Spain

Hospital de La Santa Creu I Sant Pau

Barcelona, , Spain

H. Duran i Reynals-ICO

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital General Yagüe

Burgos, , Spain

H. Provincial de Castellón

Castelló, , Spain

Hospital Universitari de Girona Dr. Josep Trueta

Girona, , Spain

Hospital Virgen de las Nieves

Granada, , Spain

Hospital Ciudad de Jaén

Jaén, , Spain

H. de la Princesa

Madrid, , Spain

H.U. Puerta de Hierro

Madrid, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Gregorio Marañon

Madrid, , Spain

Hospital Carlos Haya

Málaga, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Hospital Morales Messeguer

Murcia, , Spain

Hospital Son Dureta/ Ses Espases

Palma de Mallorca, , Spain

H. Son Llátzer

Palma de Mallorca, , Spain

Hospital nuestra señora de Valme

Seville, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

H. Gen. Univ. Valencia

Valencia, , Spain

Hospital Arnau de Vilanova

Valencia, , Spain

H. General de Vic

Vic, , Spain

Hospital Clínico Lozano Blesa

Zaragoza, , Spain

H. Clínico Lozano Blesa

Zaragoza, , Spain

Countries

Spain

References

Karachaliou N, Bracht JWP, Fernandez Bruno M, Drozdowskyj A, Gimenez Capitan A, Moran T, Carcereny E, Cobo M, Domine M, Chaib I, Ramirez JL, Camps C, Provencio M, Vergnenegre A, Lopez-Vivanco G, Majem M, Massuti B, Rosell R. Association of PALB2 Messenger RNA Expression with Platinum-Docetaxel Efficacy in Advanced Non-Small Cell Lung Cancer. J Thorac Oncol. 2019 Feb;14(2):304-310. doi: 10.1016/j.jtho.2018.10.168. Epub 2018 Nov 22.

Reference Type: DERIVED

PMID: 30472259 (View on PubMed)

Moran T, Wei J, Cobo M, Qian X, Domine M, Zou Z, Bover I, Wang L, Provencio M, Yu L, Chaib I, You C, Massuti B, Song Y, Vergnenegre A, Lu H, Lopez-Vivanco G, Hu W, Robinet G, Yan J, Insa A, Xu X, Majem M, Chen X, de Las Penas R, Karachaliou N, Sala MA, Wu Q, Isla D, Zhou Y, Baize N, Zhang F, Garde J, Germonpre P, Rauh S, ALHusaini H, Sanchez-Ronco M, Drozdowskyj A, Sanchez JJ, Camps C, Liu B, Rosell R; Spanish Lung Cancer Group, the French Lung Cancer Group and the Comprehensive Cancer Centre of Drum Tower Hospital in Nanjing; Colinet B, De Greve J, Germonpre P, Chen H, Chen X, Du J, Gao Y, Hu J, Hu W, Kong W, Li L, Li R, Li X, Liu B, Liu J, Lu H, Qian X, Ren W, Song Y, Wang L, Wei J, Wen L, Wu Q, Xiao X, Xu X, Yan J, Yang J, Yang M, Yang Y, Yin J, You C, Yu L, Yue X, Zhang F, Zhang J, Zhou Y, Zhu L, Zou Z, Baize N, Bombaron P, Chouaid C, Dansin E, Fournel P, Fraboulet G, Gervais R, Hominal S, Kahlout S, Lecaer H, Lena H, LeTreut J, Locher C, Molinier O, Monnet I, Oliviero G, Robinet G, Schoot R, Thomas P, Vergnenegre A, Berchem G, Rauh S, Al Husaini H, Aparisi F, Arriola E, Ballesteros I, Barneto I, Bernabe R, Blasco A, Bosch-Barrera J, Bover I, Calvo de Juan V, Camps C, Carcereny E, Catot S, Cobo M, De Las Penas R, Domine M, Felip E, Garcia-Campelo MR, Garcia-Giron C, Garcia-Gomez R, Garcia-Sevila R, Garde J, Gasco A, Gil J, Gonzalez-Larriba JL, Hernando-Polo S, Jantus E, Insa A, Isla D, Jimenez B, Lianes P, Lopez-Lopez R, Lopez-Martin A, Lopez-Vivanco G, Macias JA, Majem M, Marti-Ciriquian JL, Massuti B, Montoyo R, Morales-Espinosa D, Moran T, Moreno MA, Pallares C, Parera M, Perez-Carrion R, Porta R, Provencio M, Reguart N, Rosell R, Rosillo F, Sala MA, Sanchez JM, Sullivan I, Terrasa J, Trigo JM, Valdivia J, Vinolas N, Viteri S, Botia-Castillo M, Mate JL, Perez-Cano M, Ramirez JL, Sanchez-Rodriguez B, Taron M, Tierno-Garcia M, Mijangos E, Ocana J, Pereira E, Shao J, Sun X, O'Brate R. Two biomarker-directed randomized trials in European and Chinese patients with nonsmall-cell lung cancer: the BRCA1-RAP80 Expression Customization (BREC) studies. Ann Oncol. 2014 Nov;25(11):2147-2155. doi: 10.1093/annonc/mdu389. Epub 2014 Aug 27.

Reference Type: DERIVED

PMID: 25164908 (View on PubMed)

Related Links

http://www.gecp.org/

Web page of the sponsor where users can find more information about Fundación GECP studies

Other Identifiers

2007-004278-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GECP-BREC

Identifier Type: -

Identifier Source: org_study_id