Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Cisplatin

Tubulin Modulators

Antimitotic Agents

Preoperative docetaxel-cisplatin combination chemotherapy

Preoperative docetaxel monotherapy

Harubumi Kato, MD, PhD

The purpose of this study is to evaluate the safety and efficacy of the preoperative docetaxel and docetaxel-cisplatin combination in c-stage IB/II NSCLC, and select the optimal preoperative therapy for phase III trials.

Preoperative chemotherapy has substantial theoretical advantage. Several controlled trials are under way in early stage (clinical stage IB-II) nonsmall cell lung cancer (NSCLC). In each trial, platinum-based doublet chemotherapy is employed. Although platinum-based doublet is the treatment of choice for advanced NSCLC, risk/benefit balance might well be different in earlier stages. There have been no prospective randomized trials to choose an optimal preoperative chemotherapy in early stage NSCLC.

Comparison: Preoperative cisplatin-docetaxel combination versus docetaxel monotherapy in clinical stage IB/II NSCLC.

Study of Preoperative Docetaxel or Cisplatin (CDDP) + Docetaxel for C-stage IB-II Non-Small Cell Lung Cancer (NSCLC)

Randomized Phase II Study of the Induction Chemotherapy With Docetaxel Alone vs CDDP + Docetaxel for C-stage IB-II Non-Small Cell Lung Cancer (JCOG 0204-MF)

Ministry of Health, Labour and Welfare, Japan

Haruhiko Fukuda

JCOG Data Center

Carcinoma

Carcinoma, Bronchogenic

Bronchial Neoplasms

Gemcitabine

Antimetabolites

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

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

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

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

Cisplatin, Docetaxel

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

Gemcitabine, Cisplatin

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

Docetaxel, Cisplatin

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

Rafel Rossell, MD

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.

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.

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

Multicenter Phase III, Randomized Study to Evaluate Treatment Customized According to RAP80 and BRCA1 Assessment in Patients With Advanced Non-small-cell Lung Cancer

Defined as the length of time from the start of treatment to the date of the first documented progression of disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

Defined as the length of time from the start of the treatment that patients diagnosed with the disease are still alive.

Spanish Lung Cancer Group

The drugs used in this trial have been on the market for several years and the profile of safety is known. No unusual AEs has occurred in this trial.

Since the objective of the interim analysis for which the trial was closed was not the analysis of AEs, these have not been analyzed for this trial.

During the study were reported 68 cases of SAEs related to medication and 106 cases of SAEs not related to medication.

The only SUSAR was: Severe afebrile neutropenia and renal failure.

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

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

Control Group

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

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

B1: Experimental Group 1

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

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

B2 Experimental Group 2

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

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

B3 Experimental Group 3

A Control Group

Include experimental groups Arm B1+ Arm B2+ Arm B3

Experimental Group

Total

Age, Continuous

Sex: Female, Male

Spain

Region of Enrollment

Smoker

Non-smoker

No data

Smoking status

ECOG 0

ECOG 1-2

ECOG Performance Status Scale: It describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability

GRADES:

ECOG 0: Fully active. ECOG 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature ECOG 2: Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours ECOG 3: Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours ECOG 4: Completely disabled ECOG 5: Dead

ECOG

Thoracic

Extra-thoracic

Stage IV disease extension at study entrance

Squamous

NonSquamous

Histology

Median number of cycles

Low BRCA mRNA level

Intermediate BRCA mRNA level

Hight BRCA mRNA level

The expression of BRCA1 mRNA will be determined by RT- PCR in paraffin-embedded tumor samples

BRCA1 mRNA level

Low RAP80 mRNA level

Intermediate RAP80 mRNA level

Hight RAP80 mRNA level

Undetermined level RAP80 mRNA

The expression of RAP80 mRNA will be determined by RT-PCR in paraffin-embedded tumor samples

RAP 80 mRNA level

mRNA expression by a real-time PCR in paraffin-embedded tumor samples

mRNA RAP80 expression values

mRNA BRCA1 expression values

The were a early closure of the study and it was notified to comply with the regulations for early termination of the studies. clinical trials (futility analysis).

Eva Pereira

This is a futility analysis. The initial hypothesis of the clinical trial was that the experimental group as a whole was superior to the control group.

Progression Free Survival

Overall Survival

Patients with low expression of RAP 80, and with any level of BRCA1 expression:

gemcitabine 1250 mg/m2, days 1 and 8, and cisplatin 75 mg/m2, day 1. Cycles every 21 days.

Experimental Group Arm B1

Patients with intermediate or high expression of RAP 80, and with low or intermediate expression of BRCA1: docetaxel 75 mg/m2, and cisplatin 75 mg/m2, both administered on day 1, every 21 days

Experimental Group Arm B2

Patients with intermediate or high expression of RAP 80, and with high expression of BRCA1: docetaxel 75 mg/m2, day 1. Cycles every 21 days.

Experimental Group Arm B3

Overall Study

Ifosfamide

Isophosphamide mustard

Mesna

Mechlorethamine

Antineoplastic Agents, Alkylating

Alkylating Agents

Cisplatin 50 mg/m² day 1 Ifosfamide 3g/m² day 1 (+ uromitexan rescue) Gemcitabine 1 g/m² days 1 and 8 Cycles every 3 weeks

Cisplatin, Ifosfamide, Gemcitabine

Ifosfamide 3g/m² day 1 (+ uromitexan rescue) Gemcitabine 1 g/m² days 1 and 8 Cycles every 3 weeks

Ifosfamide, Gemcitabine

Cisplatin 50 mg/m² day 1 Docetaxel 75 mg/m² day 1 Cycles every 3 weeks

Cisplatin, docetaxel

Jean-Paul Sculier, MD, PhD

The purpose of this study is to determine if cisplatin-based chemotherapy, cisplatin-gemcitabine-ifosfamide or cisplatin-docetaxel, will improve survival in comparison to the combination gemcitabine-ifosfamide in patients with advanced NSCLC

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Preoperative Docetaxel or Cisplatin (CDDP) + Docetaxel for C-stage IB-II Non-Small Cell Lung Cancer (NSCLC)	NCT00132639	Pulmonary Neopl...	Preoperative do... Preoperative do...	20 Years - 74 Years	Japan Clinical Oncology Group
Study of Preoperative Docetaxel or Cisplatin (CDDP) + Docetaxel for C-stage IB-II Non-Small Cell Lung Cancer (NSCLC)	NCT00132639	Pulmonary Neopl...	Preoperative do... Preoperative do...	20 Years - 74 Years	Japan Clinical Oncology Group
Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma	NCT00617656	Non Small Cell ... BRCA1 Mutation	Cisplatin, Doce... Gemcitabine, Ci... Docetaxel, Cisp... Docetaxel	18 Years -	Spanish Lung Cancer Group
Randomised Study Comparing Three Chemotherapy Regimens in Non-small Cell Lung Cancer	NCT00622349	Carcinoma, Non-...	Cisplatin, Ifos... Ifosfamide, Gem... Cisplatin, doce...	18 Years -	European Lung Cancer Working Party
Study of Preoperative Docetaxel or Cisplatin (CDDP) + Docetaxel for C-stage IB-II Non-Small Cell Lung Cancer (NSCLC)	NCT00132639	Pulmonary Neopl...	Preoperative do... Preoperative do...	20 Years - 74 Years	Japan Clinical Oncology Group
Randomised Study Comparing Three Chemotherapy Regimens in Non-small Cell Lung Cancer	NCT00622349	Carcinoma, Non-...	Cisplatin, Ifos... Ifosfamide, Gem... Cisplatin, doce...	18 Years -	European Lung Cancer Working Party
Study to Evaluate Treatment Customized According to RAP80 and BRCA1 in Patients With Advanced Lung Carcinoma	NCT00617656	Non Small Cell ... BRCA1 Mutation	Cisplatin, Doce... Gemcitabine, Ci... Docetaxel, Cisp... Docetaxel	18 Years -	Spanish Lung Cancer Group

Spots Global Cancer Trial Database for cisplatin, docetaxel