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Trial record 2 of 57 for:    "Germ Cells Tumors" | "Carboplatin"

Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors (TAXIFIII)

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ClinicalTrials.gov Identifier: NCT01966913
Recruitment Status : Recruiting
First Posted : October 22, 2013
Last Update Posted : February 19, 2019
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Brief Summary:

High-dose chemotherapy with autologous hematopoietic stem-cell transplantation is a standard salvage treatment used in adults with germ cell tumors (Einhorn et al, J Clin Oncol 2007).

Disease prognosis following 1 to 2 intensified combinations of etoposide - carboplatin +/- ifosfamide depends on the patient's performance status (PS) at inclusion and the prior sensitivity of the disease to cisplatin. A poor PS and/or being refractory to cisplatin suggest a higher toxicity and a bad prognosis.

However, predictive factors of response to high-dose chemotherapy do not include a chemo-sensitivity phase with a semi-intensive chemotherapy excluding a platinum compound (epirubicin - paclitaxel), which still allows stem-cell harvest. The use of this chemotherapy combination induced a response in more than one third of the patients treated during disease progression in the TAXIF I study. The same strategy was tested in the TAXIF II study, which completed the inclusion of 45 patients and was closed in May 2008. Results of the TAXIF II study, are currently being analyzed; they support the hypothesis to prioritarily treat patients with a sensitive relapsed disease at the time of the high-dose administration.

A combination of a semi-intensive sequential ICE type chemotherapy plus bevacizumab was used on a highly refractory patient. A 5 months nearly complete response was achieved. Indeed, the overexpression of VEGF (Vascular Endothelial Growth Factor) has been identified as an independent risk factor in patients with germ cell tumor. Therefore, a treatment strategy using an inductive chemotherapy followed, in case of response, by a double intensification therapy in combination with a VEGF treatment, could be an interesting approach in patients with poor prognosis germ cell tumors.

The aim of this phase I/II trial is to assess the feasibility of a Bevacizumab - ICE (Ifosfamide-Carboplatin-Etoposide) high dose combination with the support of autologous hematopoietic stem cell for two intensive consecutive cycles ("tandem" intensification) in patients with a poor prognosis germ cell tumor non refractory to a front-line mobilization chemotherapy using two half intensified consecutive combinations of Epirubicin-Paclitaxel.


Condition or disease Intervention/treatment Phase
Germ Cell Tumor Drug: Bevacizumab Drug: ICE chemotherapy regimen Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors - A Phase I-II Sequential Chemotherapy Protocol of Bevacizumab (Avastin) Plus High-dose ICE (Ifosfamide - Carboplatin - Etoposide) Intensification
Study Start Date : April 2012
Estimated Primary Completion Date : March 2019
Estimated Study Completion Date : September 2020

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Arm Intervention/treatment
Experimental: bevacizumab

Two intensified treatments at 6-week intervals will start on D69 (max D76) and D111 (max J118) respectively, combining:

  • A bevacizumab treatment: 7.5 mg/kg every 3 weeks from D1 to the first intensified treatment for a total of 4 injections.
  • The ICE chemotherapy regimen:

    1. Etoposide, 300 mg/m²/d in two daily injections at 12-h intervals,
    2. Carboplatin, AUC 4/d by injections adjusted daily to the creatinine clearance,
    3. Ifosfamide, 2400 mg/m²/d,
    4. For 5 consecutive days followed by HSC reinjection and G-CSF (filgrastim- Neupogen) on D11 of each intensive cycle
Drug: Bevacizumab
Drug: ICE chemotherapy regimen
Etoposide, 300 mg/m²/d in two daily injections at 12-h intervals, Carboplatin, AUC 4/d by injections adjusted daily to the creatinine clearance, Ifosfamide, 2400 mg/m²/d, For 5 consecutive days followed by HSC reinjection and G-CSF (filgrastim- Neupogen) on D11 of each intensive cycle




Primary Outcome Measures :
  1. Response [ Time Frame: 3 months ]
    Partial response or complete response evaluated by scanography and assay for tumor marker(s) a month after the end of the 2 cycles

  2. Toxicity [ Time Frame: 6 months ]
    Safety recorded according to CTCAE-v4 criteria


Secondary Outcome Measures :
  1. complete response rate [ Time Frame: within 2 years of inclusion ]
  2. complete pathological response (pCR) or complete surgical response (sCR) [ Time Frame: within 2 years after inclusion ]
  3. overall survival [ Time Frame: within 2 years after inclusion ]
  4. response duration [ Time Frame: within 2 years after inclusion ]
  5. progression-free survival [ Time Frame: within 2 years after inclusion ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient aged 18 years or older having signed an informed consent form.
  • Germ cell tumor of gonadal origin, extra-gonadal, retro-peritoneal or primary mediastinal, excluding CNS tumors.
  • Relapsed, refractory or completely refractory disease. The patients must have received:

    • For relapsed patients, two lines of a standard chemotherapy (BEP or EP in first-line treatment, VeIP or VIP in second-line treatment)
    • For refractory or completely refractory patients, one line of a standard chemotherapy (BEP or EP)
  • First extra-gonadal tumor relapse
  • Normal laboratory tests levels usually required for intensive treatments
  • Performance status < 2.
  • Life expectancy ≥ 3 months.

Exclusion Criteria:

  • Brain metastases
  • Lesions of growing teratoma
  • Cardiovascular disease, uncontrolled hypertension
  • History of transient ischemic attacks
  • All other contraindications to bevacizumab treatment
  • Non-healing wound, active peptic ulcer or bone fracture
  • known allergy to bevacizumab or any of its excipients
  • known allergy to chemotherapy including Cremophor

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01966913


Contacts
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Contact: Frédéric SELLE, MD 33 1 56 01 64 52 frederic.selle@tnn.aphp.fr

Locations
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France
Hopital Tenon Recruiting
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris

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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01966913     History of Changes
Other Study ID Numbers: P100135
First Posted: October 22, 2013    Key Record Dates
Last Update Posted: February 19, 2019
Last Verified: February 2019
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Germ Cell Tumors
Bevacizumab
salvage therapy
Additional relevant MeSH terms:
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Carboplatin
Neoplasms, Germ Cell and Embryonal
Neoplasms
Neoplasms by Histologic Type
Bevacizumab
Etoposide
Ifosfamide
Isophosphamide mustard
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents