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Ovarian CancerPhase 1ITOV04NCT01177501

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

A Phase 1 study testing Topotecan in people with Ovarian Cancer and Relapses, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 65 years, women only
Conditions the study is for
Ovarian Cancer, Relapses
What is being tested?
Topotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteFrance
Study dates
Apr 2009to Mar 2012
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Frédéric Selle

    Paris, 75020

Other trials in France

About this study

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

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.

Read the 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
Being tested
Topotecan
Keywords
Ovarian cancer, Topotecan, Carboplatine, Higt dose chemotherapy
Medical subject headings
Ovarian Neoplasms, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TopotecanDrug

    Six sequential doses established in the absence of limiting toxicity, as follows : 7.5 - 8.0 - 8.5 - 9.0 - 10.0 mg/m²

Study groups in NCT01177501
Study groupRoleWhat they receive
TopotecanExperimentalNot described
Receives: Drug: Topotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: at 6 weeks after the first administration of topotecan

Secondary outcomes (4)

  1. Pharmacokinetic of topotecan

    Measured: At 1 and 5 days after the first administration of topotecan

  2. Pharmacokinetic of carboplatin

    Measured: At 1 and 5 days after the first administration of topotecan

  3. The response to therapy

    Measured: From the first day of the administration of topotecan to 2 years

  4. The duration of response and the overall survival

    Measured: From the first day of the administration of topotecan to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Aug 2010 (estimated)
  2. Study startApr 2009
  3. Primary completionMar 2012
  4. Study completionMar 2012

Why it stopped: choice of the principal investigator

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01177501
Sponsor's protocol ID
P 050603
Acronym
ITOV04
Status last verified
Nov 2012
First submitted
6 Aug 2010
Last updated
19 Nov 2012
Results posted
No
Data monitoring committee
Yes

Publications

  • McGuire WP, Hoskins WJ, Brady MF, Kucera PR, Partridge EE, Look KY, Clarke-Pearson DL, Davidson M. Cyclophosphamide and cisplatin versus paclitaxel and cisplatin: a phase III randomized trial in patients with suboptimal stage III/IV ovarian cancer (from the Gynecologic Oncology Group). Semin Oncol. 1996 Oct;23(5 Suppl 12):40-7.

    PubMed 8941409

  • Trimble EL, Adams JD, Vena D, Hawkins MJ, Friedman MA, Fisherman JS, Christian MC, Canetta R, Onetto N, Hayn R, et al. Paclitaxel for platinum-refractory ovarian cancer: results from the first 1,000 patients registered to National Cancer Institute Treatment Referral Center 9103. J Clin Oncol. 1993 Dec;11(12):2405-10. doi: 10.1200/JCO.1993.11.12.2405.

    PubMed 7902426

  • Lotz JP, Bouleuc C, Andre T, Touboul E, Macovei C, Hannoun L, Lefranc JP, Houry S, Uzan S, Izrael V. Tandem high-dose chemotherapy with ifosfamide, carboplatin, and teniposide with autologous bone marrow transplantation for the treatment of poor prognosis common epithelial ovarian carcinoma. Cancer. 1996 Jun 15;77(12):2550-9. doi: 10.1002/(SICI)1097-0142(19960615)77:123.0.CO;2-R.

    PubMed 8640705

  • Mulder PO, Willemse PH, Aalders JG, de Vries EG, Sleijfer DT, Sibinga CT, Mulder NH. High-dose chemotherapy with autologous bone marrow transplantation in patients with refractory ovarian cancer. Eur J Cancer Clin Oncol. 1989 Apr;25(4):645-9. doi: 10.1016/0277-5379(89)90199-5.

    PubMed 2653845

  • Dauplat J, Legros M, Condat P, Ferriere JP, Ben Ahmed S, Plagne R. High-dose melphalan and autologous bone marrow support for treatment of ovarian carcinoma with positive second-look operation. Gynecol Oncol. 1989 Sep;34(3):294-8. doi: 10.1016/0090-8258(89)90161-3.

    PubMed 2670694

  • Viens P, Maraninchi D, Legros M, Oberling F, Philip T, Herve P, Plagne R, Dufour P, Bergerat JP, Guastalla JP, et al. High dose melphalan and autologous marrow rescue in advanced epithelial ovarian carcinomas: a retrospective analysis of 35 patients treated in France. Bone Marrow Transplant. 1990 Apr;5(4):227-33.

    PubMed 2337735

  • Shpall EJ, Clarke-Pearson D, Soper JT, Berchuck A, Jones RB, Bast RC Jr, Ross M, Lidor Y, Vanacek K, Tyler T, et al. High-dose alkylating agent chemotherapy with autologous bone marrow support in patients with stage III/IV epithelial ovarian cancer. Gynecol Oncol. 1990 Sep;38(3):386-91. doi: 10.1016/0090-8258(90)90079-z. No abstract available.

    PubMed 2121627

  • Broun ER, Belinson JL, Berek JS, McIntosh D, Hurd D, Ball H, Williams S. Salvage therapy for recurrent and refractory ovarian cancer with high-dose chemotherapy and autologous bone marrow support: a Gynecologic Oncology Group pilot study. Gynecol Oncol. 1994 Aug;54(2):142-6. doi: 10.1006/gyno.1994.1183.

    PubMed 8063237

  • Murakami M, Shinozuka T, Kuroshima Y, Tokuda Y, Tajima T. High-dose chemotherapy with autologous bone marrow transplantation for the treatment of malignant ovarian tumors. Semin Oncol. 1994 Feb;21(1 Suppl 1):29-32. No abstract available.

    PubMed 8153654

  • Stiff PJ, McKenzie RS, Alberts DS, Sosman JA, Dolan JR, Rad N, McCloskey T. Phase I clinical and pharmacokinetic study of high-dose mitoxantrone combined with carboplatin, cyclophosphamide, and autologous bone marrow rescue: high response rate for refractory ovarian carcinoma. J Clin Oncol. 1994 Jan;12(1):176-83. doi: 10.1200/JCO.1994.12.1.176.

    PubMed 8270975

  • Legros M, Dauplat J, Fleury J, Cure H, Suzanne F, Chassagne J, Bay JO, Sol C, Canis M, Condat P, Choufi B, Tavernier F, Glenat C, Chollet P, Plagne R. High-dose chemotherapy with hematopoietic rescue in patients with stage III to IV ovarian cancer: long-term results. J Clin Oncol. 1997 Apr;15(4):1302-8. doi: 10.1200/JCO.1997.15.4.1302.

    PubMed 9193321

  • Stiff PJ, Bayer R, Kerger C, Potkul RK, Malhotra D, Peace DJ, Smith D, Fisher SG. High-dose chemotherapy with autologous transplantation for persistent/relapsed ovarian cancer: a multivariate analysis of survival for 100 consecutively treated patients. J Clin Oncol. 1997 Apr;15(4):1309-17. doi: 10.1200/JCO.1997.15.4.1309.

    PubMed 9193322

  • Ledermann JA, Herd R, Maraninchi D, Viens P, Buclon M, Philip T, Cure H, Lotz JP, Chauvin F, Ferrante P, Rosti G. High-dose chemotherapy for ovarian carcinoma: long-term results from the Solid Tumour Registry of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol. 2001 May;12(5):693-9. doi: 10.1023/a:1011136807190.

    PubMed 11432630

  • Rowinsky EK, Grochow LB, Hendricks CB, Ettinger DS, Forastiere AA, Hurowitz LA, McGuire WP, Sartorius SE, Lubejko BG, Kaufmann SH, et al. Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. J Clin Oncol. 1992 Apr;10(4):647-56. doi: 10.1200/JCO.1992.10.4.647.

    PubMed 1312588

  • Rivory LP, Robert J. [Pharmacology of camptothecin and its derivatives]. Bull Cancer. 1995 Apr;82(4):265-85. French.

    PubMed 10846537

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Topotecan in people with Ovarian Cancer and Relapses, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: choice of the principal investigator). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Identification of the maximum tolerated dose (MTD) of topotecan at 6 weeks (time frame: at 6 weeks after the first administration of topotecan). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01177501, which also lists 36 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2012.

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