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Phase I Trial of High-dose Topotecan in Association With Carboplatin, With Peripheral Blood Stem Cell Support in Patients With First Relapsed Ovarian Carcinoma Without Platinum-treatment Since 6-12 Months

Phase 1
18 Years
65 Years
Not Enrolling
Ovarian Cancer, Relapses

Thank you

Trial Information

Phase I Trial of High-dose Topotecan in Association With Carboplatin, With Peripheral Blood Stem Cell Support in Patients With First Relapsed Ovarian Carcinoma Without Platinum-treatment Since 6-12 Months

The combination Topotecan plus carboplatin at high doses has been published by Miles Prince
et al in 2001. In a triple combination, the authors were able to define the Maximum
Tolerated Dose (MTD) of 3.5 mg / m² / day x 5 days for topotecan, 250 mg / m² for paclitaxel
and AUC at 12 for carboplatin (46). The MTD of topotecan combined with carboplatin (AUC 16)
and VP 16 could not be determined by Carroll et al (47). However, in the study ITOV01bis
(ASCO abstract 2007 No. 1661), the MTD of topotecan was determined in combination with
cyclophosphamide at 120 mg / kg and was fixed at 9 mg/m2/jx 5 days, the same as the DMT used
in monotherapy ITOV 01).

Studies related above, the combination of high dose of topotecan and carboplatin seems
possible with a limited dose of carboplatin at AUC 20, an allocation of 5 days for both
drugs [with a fixed daily AUC 4 for carboplatin , same as the program TAXIF I in germ cell
tumors, published by our team (Annual Oncology 2004) as well as TAXIF II developed by
Tenon's hospital] with an administration time of 30 minutes daily for topotecan and 2 hours
for carboplatin.

these data justify the pattern of our study:

- established treatment of 5 consecutive days provides the best therapeutic index,

- infusion of 30 minutes, seems to give less non-haematological toxicity compare to
continuous infusion, which prevailed in the trial ITOV 01,

- Rescue by blood stem cells (collected by chemotherapy mobilization-type high-dose
cyclophosphamide followed by hematopoietic growth factors (G-CSF, Filgrastim)
reinjection is scheduled to H96 after the treatment end ,

- six sequential doses established in the absence of limiting toxicity, as follows: 7.5 -
8.0 - 8.5 - 9.0 - 9.5 - 10.0 mg/m2. Steps 9.5 mg / m² and 10 mg / m will be discussed
after approval by an independent committee in charge of the studyContinuation of
Topotecan at conventional dose can be done thanks to clinical data based on efficacy
and tolerance

Inclusion Criteria:

- Primary ovarian or tubal adenocarcinoma, or peritoneal carcinoma histologically

- 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

- 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

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Identification of the maximum tolerated dose (MTD) of topotecan at 6 weeks

Outcome Description:

Evaluation of limiting toxicities (toxic death, grade IV non-hematopoietic or haematopoietic toxicity)of topotecan

Outcome Time Frame:

at 6 weeks after the first administration of topotecan

Safety Issue:


Principal Investigator

Frédéric Selle, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Assistance Publique - Hôpitaux de Paris


France: Ministry of Health

Study ID:

P 050603



Start Date:

April 2009

Completion Date:

March 2012

Related Keywords:

  • Ovarian Cancer
  • Relapses
  • Ovarian cancer
  • Topotecan
  • Carboplatine
  • Higt dose chemotherapy
  • Carcinoma
  • Ovarian Neoplasms