Safety Study of Docetaxel/Cisplatin Induction Therapy Followed by Concurrent Chemoradiotherapy or Concurrent Chemoradiotherapy Followed by Consolidation Docetaxel/Cisplatin in NSCLC Patients

A Two Arm Phase II Study Assessing Docetaxel/Cisplatin Induction Therapy Followed by Concurrent Chemoradiotherapy or Concurrent Chemoradiotherapy Followed by Consolidation Docetaxel/Cisplatin in Patients With Locally Advanced Unresectable NSCLC (Stage IIIA-multiple cN2 or IIIB)

• Primary : To determine the safety profile of each treatment group.
• Secondary : To determine efficacy in term of overall response, disease free survival and survival at 1 and 2 years.

Study Overview

• Status: Terminated
• Conditions: Non-Small-Cell Lung Carcinoma
• Intervention / Treatment: Drug: docetaxel and cisplatin; Radiation: radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Sanofi-Aventis

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:

1. Informed consent form obtained, signed and dated before specific protocol procedures.
2. Histologically or cytologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, large cell carcinoma or a combination of these)

3. Patients must have a loco regionally advanced unresectable NSCLC;

   • Stage IIIA with clinical multiple N2 nodes (preferably with histological or cytological confirmation).

     • Patients with peripheral tumours of the lower lobe with contralateral upper mediastinal nodes at station N2 are excluded·

   • Stage IIIB T4 or N3.

     • In the T4 category, patients with pleural or pericardial effusion and multiple nodules in the same lobe are excluded.
     • Patients with T4 disease secondary to extensive and massive involvement of the great vessels are excluded.Patients should be excluded when the expected risk of pulmonary toxicity is likely to be high, e.g. V20 in excess of 35%.
4. Males or females aged between 18 and 75 years.
5. Life expectancy of at least 12 weeks.
6. WHO performance status 0 or 1.
7. Weight loss <=10% within the last 3 months.

8. Laboratory requirements at entry (within 7 days before randomization):

   • Blood cell counts:

     • Absolute neutrophils >= 2.0 x 10^9/L
     • Platelets >= 100 x 10^9/L
     • Hemoglobin >= 10 g/dl

   • Renal function:

     • Serum creatinine <=1 x the upper limit of normal (UNL). In case of borderline value of serum creatinine, the 24h creatinine clearance should be >= 60 mL/min.

   • Hepatic function:

     • Serum bilirubin <= 1 x UNL
     • ASAT and ALAT <= 2.5 x UNL
     • Alkaline phosphatase <= 5 x UNL Patients with ASAT and/or ALAT > 1.5 x UNL associated with alkaline phosphatase> 2.5 x UNL are not eligible for the study.

9. Lung function tests at entry:

   • FEV1: >= 50 % x Normal value
   • DLCO: >= 50 % x Normal value
10. Adequate cardiac function.
11. Patient with either measurable and/or non-measurable lesion (according to RECIST criteria).

Exclusion Criteria:

1. Diagnosis of small cell lung cancer.
2. Pregnant or lactating women.
3. Patients (male or female) with reproductive potential not implementing adequate contraceptive measures.
4. Prior systemic chemotherapy, immunotherapy, or biological therapy including neoadjuvant or adjuvant treatment for NSCLC.
5. Prior surgery for NSCLC, if less than 5 years from study.
6. Prior radiotherapy for NSCLC.
7. History of prior malignancies, except for cured non-melanoma skin cancer, curatively treated in-situ carcinoma of the cervix or other cancer curatively treated and with no evidence of disease for at least five years.
8. Symptomatic peripheral neuropathy Grade >= 2 except if due to trauma.

9. Other serious concomitant illness or medical conditions:

   • Congestive heart failure or angina pectoris except if it is medically controlled. Previous history of myocardial infarction within 1 year from study entry, uncontrolled hypertension or arrhythmias.
   • History of significant neurological or psychiatric disorders including dementia or seizures.
   • Active infection requiring IV antibiotics.
   • Active ulcer, unstable diabetes mellitus or other contra-indication to corticosteroid therapy.
   • Superior vena cava syndrome contra-indicating hydration.
   • Preexisting pericardial effusion.
   • Preexisting symptomatic pleural effusion.
10. Significant gastrointestinal abnormalities, including requirement for intravenous nutrition, active peptic ulcer disease, prior surgical procedures affecting absorption.
11. Distant metastasis.
12. Concurrent treatment with any other experimental anti-cancer drugs.
13. Concomitant or within 4-week period administration of any other experimental drug under investigation.
14. Significant ophthalmologic abnormalities.
15. Moderate to severe dermatitis.
16. Hypersensitivity to docetaxel, cisplatin, or any of its excipients.
17. Concomitant use of phenytoin, carbamazepin, barbiturates, or rifampicin.
18. Mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.
19. Patient unlikely to comply with protocol, i.e., uncooperative attitude, inability to return for follow-up visits, and not likely to complete the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Induction chemotherapy followed by concurrent chemoradiotherapy	Drug: docetaxel and cisplatin; Docetaxel (75 mg/m2, IV, Day 1) and cisplatin (40 mg/m2, IV, Day 1, 2) every 3 weeks for 2 cycles, followed by concurrent chemo-radiotherapy with docetaxel (20 mg/m2, IV) and cisplatin (20 mg/m2) weekly for 6 weeks + radiotherapy 2 Gy/day, 5 days per week to a total dose of 66 Gy.
Active Comparator: 2; Concurrent chemo-radiotherapy followed by consolidation chemotherapy	Radiation: radiotherapy; Docetaxel (20 mg/m2, IV) and cisplatin (20 mg/m2) weekly for 6 weeks + radiotherapy 2 Gy/day, 5 days per week to a total dose of 66 Gy followed by docetaxel (75 mg/m2, IV, Day 1) and cisplatin (40 mg/m2, IV, Day 1, 2) every 3 weeks for 2 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
overall response rate	in population of patients eligible and evaluable for response
time to progression	from the date of start treatment until progression
duration of response	only on responders

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: M COUDERC, Dr, Sanofi

Study record dates

Study Major Dates

• Study Start: May 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: December 29, 2005
• First Submitted That Met QC Criteria: December 29, 2005
• First Posted (Estimate): December 30, 2005

Study Record Updates

• Last Update Posted (Estimate): December 23, 2009
• Last Update Submitted That Met QC Criteria: December 21, 2009
• Last Verified: December 1, 2009

More Information

Terms related to this study

• 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: XRP6976B_2507; EudraCT #: 2005-001276-12