Clinical trial NCT01966913: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Germ Cell Tumor
Keywords: Germ Cell Tumors
Bevacizumab
salvage therapy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2013-10-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Response
timeFrame: 3 months
measure: Toxicity
timeFrame: 6 months
Secondary outcomes:
measure: complete response rate
timeFrame: within 2 years of inclusion
measure: complete pathological response (pCR) or complete surgical response (sCR)
timeFrame: within 2 years after inclusion
measure: overall survival
timeFrame: within 2 years after inclusion
measure: response duration
timeFrame: within 2 years after inclusion
measure: progression-free survival
timeFrame: within 2 years after inclusion
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Tenon
Study officials:
References: