Trial of High Dose Topotecan With Carboplatin in Patients With Relapsed Ovarian Carcinoma (ITOV04)

November 16, 2012 updated by: Assistance Publique - Hôpitaux de Paris

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 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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Actual)

3

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75020
        • Frédéric Selle

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Topotecan
Drug: Topotecan
Six sequential doses established in the absence of limiting toxicity, as follows : 7.5 - 8.0 - 8.5 - 9.0 - 10.0 mg/m²

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Identification of the maximum tolerated dose (MTD) of topotecan at 6 weeks
Time Frame: at 6 weeks after the first administration of topotecan
Evaluation of limiting toxicities (toxic death, grade IV non-hematopoietic or haematopoietic toxicity)of topotecan
at 6 weeks after the first administration of topotecan

Secondary Outcome Measures

Outcome Measure
Time Frame
Pharmacokinetic of topotecan
Time Frame: At 1 and 5 days after the first administration of topotecan
At 1 and 5 days after the first administration of topotecan
Pharmacokinetic of carboplatin
Time Frame: At 1 and 5 days after the first administration of topotecan
At 1 and 5 days after the first administration of topotecan
The response to therapy
Time Frame: From the first day of the administration of topotecan to 2 years
From the first day of the administration of topotecan to 2 years
The duration of response and the overall survival
Time Frame: From the first day of the administration of topotecan to 2 years
From the first day of the administration of topotecan to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Frédéric Selle, MD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

August 6, 2010

First Submitted That Met QC Criteria

August 6, 2010

First Posted (Estimate)

August 9, 2010

Study Record Updates

Last Update Posted (Estimate)

November 19, 2012

Last Update Submitted That Met QC Criteria

November 16, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P 050603

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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