A Phase II Study of Doxorubicin, Cyclophosphamide and Vindesine With Valproic Acid in Patients With Refractory or Relapsing Small Cell Lung Cancer After Platinum Derivatives and Etoposide

Study Overview
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Brief Summary
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The primary aim of this study is to determine if the addition of valproic acid to a combination of adriamycin, cyclophosphamide and vindesine could increase progression-free survival in patients relapsing after first-line chemotherapy including platinum derivatives, cisplatin or carboplatin, and etoposide.

Official Title
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A Phase II Study of Doxorubicin, Cyclophosphamide and Vindesine With Valproic Acid in Patients With Refractory or Relapsing Small Cell Lung Cancer After Platinum Derivatives and Etoposide

Conditions
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Small Cell Lung Carcinoma

Intervention / Treatment
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* Drug: Adriamycin, cyclophosphamide, vindesine, valproic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological diagnosis of small-cell lung cancer (SCLC) SCLC refractory to prior chemotherapy regimen including platinum derivatives (cisplatin or carboplatin) and etoposide, either primary refractory (immediate progression or recurrence less than 3 months after the end of previous chemotherapy) or secondary refractory (sensitive patients to platinum plus etoposide in first-line, progressing or recurring less than 3 months after reintroduction of the same chemotherapy). At least one evaluable or measurable lesion Availability for participating in the detailed follow-up of the protocol Signed informed consent. Exclusion Criteria: Patient who were previously treated with anthracyclin or vinca-alcaloid derivatives or cyclophosphamide Performance status < 60 on the Karnofsky scale A history of prior malignant tumour, except non-melanoma skin cancer or in situ carcinoma of the cervix or of the bladder or cured malignant tumour (more than 5-year disease free interval) A history of prior HIV infection Polynuclear cells < 2,000/mm³ Platelet cells < 100,000/mm³ Abnormal coagulation tests (aPTT, PTT, prothrombin time) and/or decreased fibrinogen Serum bilirubin >1.5 mg/100 ml Transaminases more than twice the normal range Serum creatinine > 1.5 mg/100 ml Recent myocardial infarction (less than 3 months prior to date of diagnosis) Congestive cardiac failure (ejection fraction of the left ventricle < 50%) or uncontrolled cardiac arrhythmia Uncontrolled infectious disease Active epilepsy needing a specific treatment Concomitant treatment with IMAO, carbamazepine, mefloquine, phenobarbital, primidone, phenytoïn, lamotrigine, zidovudine Pregnancy or refusal to use active contraception A known allergy to valproic acid and/or doxorubicin, cyclophosphamide, vindesine Serious medical or psychological factors which may prevent adherence to the treatment schedule.

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Chemotherapy regimen (adriamycin, cyclophosphamide, vindesine) plus valproic acid | Drug: Adriamycin, cyclophosphamide, vindesine, valproic acid<br>* Adriamycin 45 mg/m² day 1 IV Cyclophosphamide 1 g/m² day 1 IV Vindesine 3 mg/m² day 1 IV Valproic acid 20-30 mg/kg/day from day -7 until the end of treatment, orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six-months progression-free survival |  | The period between the day of registration and the date of first progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Survival will be dated from the date of registration | 
| Response rate |  | Every three cycles of chemotherapy | 
| Toxicity |  | After each course of chemotherapy and at the end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small cell lung carcinoma, Valproic acid, Adriamycin, Cyclophosphamide, Vindesine, Second-line chemotherapy