Trial of High Dose Topotecan With Carboplatin in Patients With Relapsed Ovarian Carcinoma

The early relapse of ovarian cancer occurring within 6 months of chemotherapy including platinum regimen are called relapses 'platinum resistant' consecutively patients die quickly of their disease. For relapses occurring between 6 and 12 months, no recommendation occur and few studies are conducted. Therefore it seems interesting to develop a research on intensive chemotherapy using a combination of carboplatin (a drug widely used in most ovarian cancer) with Topotecan , use in a high dose protocol. Topotecan has demonstrated its efficacy in relapse ovarian cancer and its possible use in high doses, a recent study (ITOV01) have demonstrated the feasibility of dose escalation of topotecan monotherapy (MTD set at 9 mg / m² / dx 5 days). This project is a feasibility research of the combination of topotecan and carboplatin in a high dose escalation protocol for early ovarian cancer relapse occurring 6 to 12 months after conventional chemotherapy-based platinum salts.

Sex

Female

Minimum age

18 Years

Maximum age

65 Years

Inclusion Criteria:

* Primary ovarian or tubal adenocarcinoma, or peritoneal carcinoma histologically proved
* Age between 18 and 65
* ECOG criteria £ 2
* Patients with first relapsed ovarian carcinoma without platinum-treatment since 6-12 months and after first-line therapy with platinum salt and taxanes together or successively
* Negative viral serology (HbS, HbC and HIV)
* Informed consent
* Patients with social security

Exclusion Criteria:

* Refractory (relapse \< 6 months) or sensitive (relapse \> 12 months) relapsed ovarian carcinoma
* Life expectancy \< 3 months
* Previous treatment with pelvic radiography
* Previous treatment with Topotecan or other topoisomer I inhibitor
* Non resolutive intestinal obstruction under symptomatic treatment
* Creatinine \> or equal at 1.25N and/or creatinine clearance \< or equal at 60 ml/mn
* Bilirubin \> 1.25N ; transaminase and alkaline phosphatase \> 2N (3N if hepatic metastases were present)
* Abnormal heart (ultrasound only) (FR \< 30%; FEVG \< 50%)
* White blood cells \< or equal at 4.0 x 109/L, Neutrophils \< or equal at 1.5 x 109/L, platelets \< or equal at 100 x 109/L
* Neuropathy: grade \> or equal at 2
* Epilepsy
* Symptomatic cerebral metastases
* Serious psychiatric pathology
* Uncontrolled serious infection
* Patient that already received peripheral blood stem cell support
* Haematopoeitic growth factors allergy
* More than one line chemotherapy
* Impossibility to use an central veinous access
* Hypersensibility to carboplatin or other platinum containing products
* Participation to an other clinical trial
* Absence of effective contraception

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