Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors

Brief Title

Salvage Chemotherapy for Poor Prognosis Germ Cell Tumors

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

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.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional

Primary Outcome

Response

Secondary Outcome

 complete response rate

Condition

Germ Cell Tumor

Intervention

Bevacizumab

Study Arms / Comparison Groups

 bevacizumab

Description:  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:
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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

30

Start Date

April 2012

Completion Date

September 2020

Primary Completion Date

March 2019

Eligibility 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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 33 1 56 01 64 52, [email protected]

Location Countries

France

Location Countries

France

NCT ID

NCT01966913

Organization ID

P100135

Responsible Party

Sponsor

Study Sponsor

Assistance Publique - Hôpitaux de Paris

Study Sponsor

, , 

Verification Date

February 2019