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

This study has been terminated.
(choice of the principal investigator)
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01177501
First received: August 6, 2010
Last updated: November 16, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Relapses
Drug: Topotecan
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Identification of the maximum tolerated dose (MTD) of topotecan at 6 weeks [ Time Frame: at 6 weeks after the first administration of topotecan ] [ Designated as safety issue: Yes ]
    Evaluation of limiting toxicities (toxic death, grade IV non-hematopoietic or haematopoietic toxicity)of topotecan


Secondary Outcome Measures:
  • Pharmacokinetic of topotecan [ Time Frame: At 1 and 5 days after the first administration of topotecan ] [ Designated as safety issue: No ]
  • Pharmacokinetic of carboplatin [ Time Frame: At 1 and 5 days after the first administration of topotecan ] [ Designated as safety issue: No ]
  • The response to therapy [ Time Frame: From the first day of the administration of topotecan to 2 years ] [ Designated as safety issue: No ]
  • The duration of response and the overall survival [ Time Frame: From the first day of the administration of topotecan to 2 years ] [ Designated as safety issue: No ]

Enrollment: 3
Study Start Date: April 2009
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: Topotecan

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
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01177501

Locations
France
Frédéric Selle
Paris, France, 75020
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Frédéric Selle, MD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01177501     History of Changes
Other Study ID Numbers: P 050603
Study First Received: August 6, 2010
Last Updated: November 16, 2012
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Ovarian cancer
Topotecan
Carboplatine
Higt dose chemotherapy

Additional relevant MeSH terms:
Carcinoma
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carboplatin
Topotecan
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 19, 2014