A Phase II Trial of Cisplatin-Docetaxel Induction Plus Concurrent 3-D Conformal Radiotherapy and Weekly Chemotherapy (TAXCIS)

Cisplatin-Docetaxel Induction Plus Concurrent 3-D Conformal Radiotherapy and Weekly Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients: A Phase II Trial

Concurrent chemoradiotherapy (CHRT) is the standard of care for unresectable locally advanced stage III non-small cell lung cancer. However, the optimal combination remains unclear. The aim of this study is to evaluate the efficacy of 2 induction chemotherapy cycles (days 1 and 22) with docetaxel 75 mg/m2 and cisplatin 75 mg/m2 followed by concurrent chemotherapy (weekly docetaxel-cisplatin, 20 mg/m2) and 3-D conformal radiotherapy for 6 weeks (66 Gy/5 fractions per week/2 Gy per fraction). ). The primary endpoint is the response rate. Secondary objectives are toxicity, time to progression, and overall survival.

Study Overview

• Status: Completed
• Conditions: Locally Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Radiation: concomitant radiotherapy; Drug: Cisplatin

Detailed Description

Lung cancer is the most common malignancy among men in most countries and constitutes the leading cause of cancer death worldwide. Non-small cell histology represents roughly 80% of lung cancer cases comprising one third of patients with stage III, locally-advanced disease at diagnosis. Some stage IIIA cancers are considered resectable but many stage IIIA (with bulky N2) and stage IIIB (T4 any N M0, any T N3M0) cancers are considered unsuitable for surgery. However, some authors have shown that surgery after chemoradiotherapy (CHRT) is beneficial for at least progression-free survival (PFS). Since the 90s, CHRT has become the cornerstone of inoperable locally advanced non-small cell lung cancer (NSCLC). A meta-analysis of 52 randomized studies showed a survival improvement of 3% at 2 years and 2% at 5 years for patients treated with CHRT versus radiotherapy alone [6]. Concomitant chemoradiation was demonstrated to be better than sequential administration in terms of overall survival (OS) in 3 out of 4 randomized studies with esophagitis as the dose-limiting toxicity. Nevertheless, the median survival was around 16 months and improvement is needed. To better control micrometastatic disease and reduce distant relapses, one possibility is to increase radiosensitization with higher doses of chemotherapy.The aim of this phase II study is to evaluate the anti-tumoral activity of a weekly docetaxel-cisplatin combination administered concurrently with radiotherapy after 2 induction cycles with the same drugs.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• histologically or cytologically confirmed NSCLC,
• stage IIIB (excluding malignant pleural or pericardial effusions, tumoral volume exceeding one radiation field,
• N3 supraclavicular, and contralateral hilar nodal involvement) or inoperable stage IIIA defined by the new International Staging System [21],
• 18 ≤ age ≤ 75 years,
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2,
• weight loss <10%,
• at least one measurable lesion according to RECIST 1.0 criteria,
• adequate hematopoietic function (absolute neutrophil count ≥2 × 109/l, platelets ≥100 × 109/l, and hemoglobin level ≥10g/dl), adequate hepatic function [total serum bilirubin less than or equal to the institutional upper limit of normal (ULN), aspartate aminotransferase ≤1.5× ULN, and alkaline phosphatase ≤5× ULN], and adequate renal function (serum creatinine ≤1.5× ULN).

Exclusion Criteria:

• patients previously treated with radiotherapy or chemotherapy for NSCLC,
• previous cancer except basocellular carcinoma and in situ carcinoma of the cervix curatively treated and other cancers curatively treated for at least 5 years,
• peripheral neuropathy NCI-CTC grade ≥2,
• noncontroled severe disease,
• pregnant or breast-feeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Radiochemotherapy; Induction chemotherapy with docetaxel and cisplatine and concomitant radiotherapy	Drug: Docetaxel; Induction chemotherapy; Radiation: concomitant radiotherapy; Pulmonary and mediastinal radiotherapy; Drug: Cisplatin; Induction chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the antitumor activity of Docetaxel - Cisplatin and concomitant thoracic radiotherapy after Docetaxel - Cisplatin induction chemotherapy in patients with locally advanced non-operable NSCLC by tumor response rate	Tumor Response rate between 6 and 8 weeks according to RECIST 1.0 criteria after the end of radiotherapy (except in the case of early progression) that patients: having received at least 4 weekly injections of Docetaxel and Cisplatin,; who have received the full radiotherapy treatment (except in case of cessation for toxicity, in which case the patients will be evaluable).	up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival and at 12 months	To evaluate the overall survival at 12 months between the first day of treatment to the death	up to 3 years
Response delay	Complete response delay evaluated between the day of the complete response to the progression and partial response between the first day of the treatment and the progression	up to 3 years
Progression Free Survival	To evaluate Progression free survival according to RECIST criteria	up to 3 years
Tolerance profile of the association in terms of immediate and delayed toxicity	To evaluate early and late toxicity according to the NCI-CTC	up to 3 years
Quality of Life evaluation (EORTC QLQ-C30 and QLQ-LC13)	To evaluate the quality of life at inclusion, at the end oh chemotherapy, 2 months after the radiotherapy and every 3 months until end of study	up to 3 years

Collaborators and Investigators

• Sponsor: Centre Antoine Lacassagne

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2004
• Primary Completion (Actual): October 31, 2010
• Study Completion (Actual): October 31, 2011

Study Registration Dates

• First Submitted: November 30, 2017
• First Submitted That Met QC Criteria: December 12, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 12, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Concurrent 3-D chemoradiotherapy,Docetaxel,Cisplatin,Chemotherapy ·
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Cisplatin
• Other Study ID Numbers: 2004/07

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No