Non-small-cell Lung Cancer
Conditions
Keywords
SCAT, BRCA1, BRCA1 mRNA Levels, ADJUVANT, LUNG, GECP-SCAT
Brief summary
Randomized Study of Customized Adjuvant Chemotherapy based on BRCA1 mRNA Levels in Completely Resected stages II-IIIA Non-Small-Cell Lung Cancer Patients.
Detailed description
Randomized, phase III, predictive pharmacogenomic, open, prospective, international, multicenter study in patients with non-small-cell lung carcinoma (NSCLC) after complete resection and with N1 or N2 involvement
Interventions
DRUGDocetaxel/Cisplatin control
Docetaxel 75 mg/m2 and cisplatin 75 mg/m2 day 1, 4 cycles
DRUGDocetaxel
Docetaxel 75 mg/m2 day 1, 4 cycles
Gemcitabine 1250 mg/m2, day 1 and 8 and cisplatin 75 mg/m2 day 1, 4 cycles
Docetaxel 75 mg/m2 and cisplatin 75 mg/m2 day 1, 4 cycles
Sponsors
Spanish Lung Cancer Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histological confirmation of non-small-cell lung carcinoma. * Complete surgical resection of the disease. * Tumoral tissue available for molecular analysis. * N1 (stage II) or N2 (stage IIIA) lymph node involvement in the study of the operative piece. * Men or women age 18 years or older. * Patients with a performance status of 2 or less according to the ECOG classification. * Patients with the following laboratory results: ANC \< 1500/L, Hb \< 10 g/dL, platelets \<100,000/L, bilirubin \< 1.0 mg/dL, AST and ALT \< 1.5 upper limit of normality, creatinine clearance \< 60 mL/min. * Complete recovery from surgery within 6 weeks. * Patients who have given written informed consent before initiating any specific study screening procedure.
Exclusion criteria
* Patients who have received previously chemotherapy or radiotherapy for the study disease. * Impossibility of complying with chemotherapy treatment due to cultural or geographic circumstances. * Patients with active infection, heart disease, or any other serious disease, in the judgment of the investigator. * Women who are pregnant or in the period of lactation. * Patients with a previous diagnosis of malignant disease in the last five years except for carcinoma in situ of the uterine cervix or skin cancer other than melanoma. * Patients under treatment with investigational agents.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Estimated Overall Survival | 5 years | To assess and compare the overall survival estimated at 5 years of both treatment groups (Control arm vs Experimental arm). Overall survival:The proportion of participants in treatment group who are still alive for a certain period of time after inclusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival | 5 years | To assess the disease-free survival of both treatment groups. Disease-free survival: will be calculated from the date of surgery until there is some clinical evidence of disease progression or the date of death due to the disease. |
Countries
Spain
Participant flow
Recruitment details
The recruitment was 500 patients (intention to treat patient) in 47 centers between June 2007 and May 2013.
Pre-assignment details
Screening details: Experimental arm: according to the BRAC1 levels of the tumor tissue, receive different combination of treatment.
Participants by arm
| Arm | Count |
|---|---|
| Control Arm Docetaxel/Cisplatin: Docetaxel 75 mg/m2, and cisplatin 75 mg/m2, both on day 1, every 21 days. Total cycles: 4. | 101 |
| Experimental Arm Experimental group, according to the BRAC1 levels of the tumor tissue, one of the following treatments will be assigned:
* Low expression of BRCA1 gemcitabine 1250 mg / m2, days 1 and 8, and cisplatin 75 mg / m2, day 1. Cycles every 21 days. Total cycles: 4
* Intermediate expression levels of BRCA1 docetaxel 75 mg / m2, and cisplatin 75 mg / m2, both administered on day 1, every 21 days. Total cycles: 4.
* High expression levels of BRCA1 docetaxel 75 mg / m2, day 1. Cycles every 21 days. Total cycles: 4. | 355 |
| Total | 456 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inclusion Error | 1 | 7 |
| Overall Study | Not receive study treatment | 6 | 30 |
Baseline characteristics
| Characteristic | Experimental Arm | Total | Control Arm |
|---|---|---|---|
| Age, Continuous | 61 years | 62 years | 63 years |
| Histology Adenocarcinomas | 175 participants | 222 participants | 47 participants |
| Histology Other | 25 participants | 33 participants | 8 participants |
| Histology Squamous | 155 participants | 201 participants | 46 participants |
| Region of Enrollment Spain | 355 participants | 456 participants | 101 participants |
| Sex: Female, Male Female | 74 Participants | 96 Participants | 22 Participants |
| Sex: Female, Male Male | 281 Participants | 360 Participants | 79 Participants |
| Smoking habit Former smoker | 221 participants | 283 participants | 62 participants |
| Smoking habit Never smoker | 32 participants | 43 participants | 11 participants |
| Smoking habit Smoker | 102 participants | 130 participants | 28 participants |
| Stage IIA | 38 participants | 52 participants | 14 participants |
| Stage IIB | 142 participants | 179 participants | 37 participants |
| Stage IIIA | 175 participants | 225 participants | 50 participants |
| Staging N N1 | 215 participants | 277 participants | 62 participants |
| Staging N N2 | 140 participants | 179 participants | 39 participants |
| Staging T T1 | 68 participants | 90 participants | 22 participants |
| Staging T T2 | 230 participants | 294 participants | 64 participants |
| Staging T T3 | 57 participants | 72 participants | 15 participants |
| Treatment according to BRCA1 level Control: Docetaxel and Cisplatin | 0 participants | 101 participants | 101 participants |
| Treatment according to BRCA1 level Experimental BRCA1 High: Docetaxel | 101 participants | 101 participants | 0 participants |
| Treatment according to BRCA1 level Experimental: BRCA1 Low: Gemcitabine / Cisplatin | 155 participants | 155 participants | 0 participants |
| Treatment according to BRCA1 level Experimental BRCA1 medium: Docetaxel / Cisplatin | 99 participants | 99 participants | 0 participants |
| Treatment compliance Completed | 307 participants | 391 participants | 84 participants |
| Treatment compliance Not completed | 48 participants | 65 participants | 17 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 108 | 8 / 392 |
| other Total, other adverse events | 105 / 108 | 384 / 392 |
| serious Total, serious adverse events | 36 / 108 | 66 / 392 |
Outcome results
Primary
Estimated Overall Survival
To assess and compare the overall survival estimated at 5 years of both treatment groups (Control arm vs Experimental arm). Overall survival:The proportion of participants in treatment group who are still alive for a certain period of time after inclusion.
Time frame: 5 years
Population: Only those patients validated by protocol. Patients not valid by protocol will be all those who, having given their informed consent do not receive the study treatment because of any reason and/or those patients who after treatment with chemotherapy do not have a minimum of six months of follow-up.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Arm | Estimated Overall Survival | Control arm vs Experimental arm | 0.54 proportion of participants |
| Control Arm | Estimated Overall Survival | Control arm vs Gemcitabine /Cisplatin Experimental arm | 0.54 proportion of participants |
| Control Arm | Estimated Overall Survival | Control arm vs Docetaxel /Cisplatin Experimental arm | 0.54 proportion of participants |
| Control Arm | Estimated Overall Survival | Control arm vs Docetaxel Experimental Arm | 0.54 proportion of participants |
| Experimental Arm | Estimated Overall Survival | Control arm vs Docetaxel Experimental Arm | 0.60 proportion of participants |
| Experimental Arm | Estimated Overall Survival | Control arm vs Experimental arm | 0.56 proportion of participants |
| Experimental Arm | Estimated Overall Survival | Control arm vs Docetaxel /Cisplatin Experimental arm | 0.53 proportion of participants |
| Experimental Arm | Estimated Overall Survival | Control arm vs Gemcitabine /Cisplatin Experimental arm | 0.56 proportion of participants |
Comparison: Based on the relevant clinical evidence of the prognostic and predictive value of BRCA1, proposes the present study with which it is intended to demonstrate that adjuvant chemotherapy Individualized based on BRCA1 expression (Experimental arm), it is more effective than chemotherapy without individualize based (Control arm) in patients with completely resected stage II-IIIA NSCLC.p-value: 0.7395% CI: [0.689, 1.298]Log Rank
Secondary
Disease Free Survival
To assess the disease-free survival of both treatment groups. Disease-free survival: will be calculated from the date of surgery until there is some clinical evidence of disease progression or the date of death due to the disease.
Time frame: 5 years
Population: Participants are analyzed by protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Arm | Disease Free Survival | 38.7 Month |
| Experimental Arm | Disease Free Survival | 32.7 Month |
Comparison: Control Arm v Experimental Armp-value: 0.75395% CI: [63.5, 95.1]Log Rank
Comparison: Control Arm v Experimental Armp-value: 0.02595% CI: [28, 38.7]Log Rank