Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors (TAXIFIII)

February 18, 2019 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2
  • 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, 75012
        • Recruiting
        • Hopital Tenon

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
3 months
Toxicity
Time Frame: 6 months
Safety recorded according to CTCAE-v4 criteria
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
complete response rate
Time Frame: within 2 years of inclusion
within 2 years of inclusion
complete pathological response (pCR) or complete surgical response (sCR)
Time Frame: within 2 years after inclusion
within 2 years after inclusion
overall survival
Time Frame: within 2 years after inclusion
within 2 years after inclusion
response duration
Time Frame: within 2 years after inclusion
within 2 years after inclusion
progression-free survival
Time Frame: within 2 years after inclusion
within 2 years after inclusion

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

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, 2012

Primary Completion (Anticipated)

March 1, 2019

Study Completion (Anticipated)

September 1, 2020

Study Registration Dates

First Submitted

October 11, 2013

First Submitted That Met QC Criteria

October 17, 2013

First Posted (Estimate)

October 22, 2013

Study Record Updates

Last Update Posted (Actual)

February 19, 2019

Last Update Submitted That Met QC Criteria

February 18, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P100135

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.

Clinical Trials on Germ Cell Tumor

Clinical Trials on Bevacizumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Indonesia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe