Clinical trial NCT00617656: Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma
Official title: Multicenter Phase III, Randomized Study to Evaluate Treatment Customized According to RAP80 and BRCA1 Assessment in Patients With Advanced Non-small-cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
BRCA1 Mutation
Keywords: Lung Cancer
Chemotherapy
Personalized medicine
Lead sponsor: Spanish Lung Cancer Group
Sponsor class: OTHER
First posted: 2008-02-18
Enrollment: 382
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival
timeFrame: From the day of start of treatment until first documented progression or death due to any cause,up to 18 months.
Secondary outcomes:
measure: Overall Survival
timeFrame: From the date of start of the treatment until death or end of follow up, up to 18 months.
Other outcomes:
Locations:
city: Alcoi
country: Spain
facility: H. Virgen de los Lirios
state: Alicante
city: Badalona
country: Spain
facility: H. Germans Trias i Pujol
state: Barcelona
city: Manresa
country: Spain
facility: Hospital D'Althaia
state: Barcelona
city: Mataró
country: Spain
facility: Hospital de Mataró
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Bizkaia
city: Cordoba
country: Spain
facility: Hospital Reina Sofía
state: Córdoba
city: Alcorcon
country: Spain
facility: F.H.Alcorcón
state: Madrid
city: Leganés
country: Spain
facility: H. Severo Ochoa
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Clinica Quiron
state: Madrid
city: Pozuelo De Alarcón
country: Spain
facility: Hospital Universitario Quirón Madrid
state: Madrid
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Calatayud
country: Spain
facility: Hospital Ernest Lluch
state: Zaragoza
city: A Coruña
country: Spain
facility: H. Juan Canalejo
city: A Coruña
country: Spain
facility: H. Santiago de Compostela
city: Alicante
country: Spain
facility: H. Gral. Alicante
city: Almería
country: Spain
facility: H. Torrecárdenas
city: Almería
country: Spain
facility: Hospital Torrecárdenas
city: Barcelona
country: Spain
facility: H. Clinic i Provincial
city: Barcelona
country: Spain
facility: H. Universitario Quirón Dexeus
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu I Sant Pau
city: Barcelona
country: Spain
facility: H. Duran i Reynals-ICO
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Burgos
country: Spain
facility: Hospital General Yagüe
city: Castelló
country: Spain
facility: H. Provincial de Castellón
city: Girona
country: Spain
facility: Hospital Universitari de Girona Dr. Josep Trueta
city: Granada
country: Spain
facility: Hospital Virgen de las Nieves
city: Jaén
country: Spain
facility: Hospital Ciudad de Jaén
city: Madrid
country: Spain
facility: H. de la Princesa
city: Madrid
country: Spain
facility: H.U. Puerta de Hierro
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Murcia
country: Spain
facility: Hospital Morales Messeguer
city: Málaga
country: Spain
facility: Hospital Carlos Haya
city: Málaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Palma De Mallorca
country: Spain
facility: Hospital Son Dureta/ Ses Espases
city: Palma De Mallorca
country: Spain
facility: H. Son Llátzer
city: Sevilla
country: Spain
facility: Hospital nuestra señora de Valme
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: H. Gen. Univ. Valencia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Vic
country: Spain
facility: H. General de Vic
city: Zaragoza
country: Spain
facility: Hospital Clínico Lozano Blesa
city: Zaragoza
country: Spain
facility: H. Clínico Lozano Blesa
Study officials:
affiliation: Principal Investigator of Fundación Grupo Español de Cáncer de Pulmón
name: Rafel Rossell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.