NSCLC Relapse Therapy After Surgery and Peri-operative Chemotherapy

Study Overview
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Brief Summary
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Relapses after perioperative chemotherapy and surgery

Detailed Description
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As chemotherapy gains wider acceptance for the treatment of earlier stages of NSCLC, particularly in the adjuvant and neoadjuvant setting, physicians face a growing population of high performance status patients who have relapsed after their first-line chemotherapy. The type of second-line chemotherapy after initial adjuvant or neoadjuvant treatment with a platinum-based regimen remains largely undefined. Some might consider rechallenging patients with a platinum based doublet whereas others might treat these patients with a monochemotherapy (pemetrexed or docetaxel). Most relapses occurring after perioperative chemotherapy and surgery are non surgical locally advanced relapses or metastatic diseases. Some differences exist between these post surgical relapses and the progressions occurring after the first line non surgical treatment of a stage III/IV. Patients are most often in a good condition (performance status 0-1). Progression is often asymptomatic and diagnosed in the post surgical follow up. The dose of chemotherapy previously administered is lower than that administered in first line of a stage III/IV. The time between the first line of treatment and the treatment of the relapse is longer. These differences might be associated with a more chemosensitive disease and thus might be the rationale of using a platinum containing doublet instead of the classical mono chemotherapy docetaxel or pemetrexed. Thus, the current study has been designed to answer these questions.

Official Title
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Comparison of 2 Chemotherapy Regimens in Non-small-cell Lung Cancer (NSCLC) Patients Relapsing After Surgery and Peri-operative Chemotherapy. A Randomized Phase III Study.

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Chemotherapy with platine
* Drug: Chemotherapy without Cisplatine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with histologically or cytologically confirmed inoperable non-small cell-lung cancer not eligible for curative radio-therapy (local or metastatic relapse). Previous history of adjuvant or neoadjuvant chemotherapy (at least 2 full cycles of a platinum containing regimen) Initial stage pT1N0 to pT3N2 (TNM classification 1999), complete resection. T4 tumours (several nodules in the same lobe) and M1 tumours (several nodules in the same lung) N0-2 completely resected are allowed to inclusion. Histological complete response tumours (pT0N0) after neoadjuvant chemotherapy are allowed to inclusion. At least one unidimensionally measurable disease (RECIST criteria) (lesions must have clearly defined margins on X-ray, CT-scan, MRI or ultra-sound (US) examination and should measure at least 1 cm if assessed by CT, MRI or US and at least 2 cm if assessed by X-ray, target lesions should be selected outside a previously irradiated field ). PET scans and ultra sonography are not allowed ECOG Performance status 0 to 1). Patients with adequate biological functions: Written informed consent from patient. The effects of docetaxel, cisplatin and carboplatin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because docetaxel, cisplatin and carboplatin as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Life expectancy > 12 weeks Patient compliance and geographic proximity that allow adequate follow-up. Patient affiliated to a social insurance program Exclusion Criteria: Previous treatment with docetaxel. Hypersensitivity to docetaxel, cisplatin, carboplatin or polysorbate 80 (excipient). Previous history of cancer other than Non small cell lung cancer, in situ carcinoma of the uterine cervix and basal cell carcinoma of the skin. Patients previously treated by an investigational agent in the last 30 days. Patient treated with preoperative platin based chemotherapy, achieving a progression of disease after treatment evaluation. Patients non responders to preoperative chemotherapy and whose tumor specimen did not disclose any necrosis nor tumoral modification thus confirming the lack of chemosensitivity to platin based chemotherapy Patient treated with platin based adjuvant chemotherapy, relapsing within the first 6 months after surgery. Patients with a peripheral neuropathy grade CTC >= 2 Patients unable to fulfill protocol requirements Serious concomitant morbidity incompatible with the study (at the discretion of the investigator). Relapse within the month following lung cancer resection or adjuvant chemotherapy Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Significant loss of weight (> 10 %) in the 6 weeks preceding patient selection. Concomitant administration of another anti cancer treatment Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued. Patient under legal protection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: Chemotherapy with platine<br>* Docetaxel 75 mg/m² D1 + Cisplatine 75 mg/m² or Carboplatin AUC5 D1 (D1=D22, 4 cycles) Docetaxel 75 mg/m² D1 (D1=D22, 2 cycles if disease control)<br>|
| Active Comparator: B<br>Docetaxel monotherapy | Drug: Chemotherapy without Cisplatine<br>* Docetaxel 75 mg/m² D1 (D1=D22, 4 cycles) Docetaxel 75 mg/m² D1 (D1=D22, 2 cycles if disease control)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression-free survival (PFS) |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC relapse after adjuvant chemotherapy