Therapy Optimization Trial for the Treatment of Relapsed or Refractory Brain Tumors in Children (HIT-REZ-2005)

University Hospital Bonn (UKB)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Recurrent Brain Tumors; Supratentorial PNETs; Medulloblastomas; Ependymomas

Treatments: Drug: etoposide; Drug: temozolomide, thiotepa; Drug: trofosfamide, etoposide; Drug: thiotepa, carboplatin, etoposide; Drug: temozolomide; Drug: intraventricular etoposide; Procedure: autologous stem cell transplantation; Drug: carboplatin

Study type: Interventional

Funder types: Other

Identifiers

NCT00749723

DKS 2006.01, 2008.17, 2012.03 (Other Grant/Funding Number)

EUDRACT 2005-002618-40

EC-105/05 (Other Identifier)

BfArM-4030755 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to improve overall survival while maintaining a good quality of life in pediatric patients with refractory or recurrent brain tumors (medulloblastomas, supratentorial PNETs, ependymomas WHO grade II and III). Response to different chemotherapy options (intravenous versus oral chemotherapy, intraventricular chemotherapy) as part of a multimodal therapy will be assessed. Progression-free, overall survival and toxicity will be evaluated additionally.

Full description

Parts of the study:

P-HIT-REZ-2005: a trial for the treatment of relapsed PNETs (medulloblastomas,supratentorial PNETs)

E-HIT-REZ-2005: a trial for the treatment of relapsed ependymomas (Phase II-Study with temozolomide)

Phase II-Study: intraventricular therapy with etoposide in neoplastic meningitis in relapsed PNETs and ependymomas with subarachnoid tumor manifestation (window study)

Enrollment: 174 patients

Sex: All

Ages: 3 months to 30 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Disease Characteristics

• Histologically confirmed Medulloblastoma, cerebral PNET or Ependymoma
• Refractory or relapsed disease
• Measurable disease by MRI or detection of tumor cells in cerebrospinal fluid Patients characteristics
• Performance status ECOG ≥ 3 or Karnofsky Status ≥ 40%
• Life expectancy ≥ 8 weeks

Hematological:

• Absolute leukocyte count ≥ 2.0 x 10^9 /l
• Hemoglobin ≥ 10g/dl
• Platelet count ≥ 70 x 10^9/l

Renal:

• Creatinine no greater than 1.5 times UNL
• No overt renal disease

Hepatic:

• Bilirubin less than 2.5 times UNL
• AST and ALT less than 5 times UNL
• No overt hepatic disease

Pulmonary:

• No overt pulmonary disease

Cardiovascular:

• No overt cardiovascular disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled infection Prior concurrent therapy
• More than 2 weeks since prior systemic chemotherapy
• More than 4 weeks since prior radiotherapy
• No other concurrent anticancer or experimental drugs Examinations required
• Examination of lumbar CSF
• Cranial and spinal MRI within 14 days prior to start of treatment

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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174 participants in 4 patient groups

1: P-HIT-REZ 2005

Experimental group

Description:

intravenous chemotherapy with carboplatin/etoposide,followed by * high dose chemotherapy with thiotepa, carboplatin, etoposide and autologous stem cell transplantation if patient have achieved a complete remission or * maintenance therapy with oral trofosfamide, etoposide

Treatment:

Drug: carboplatin

Procedure: autologous stem cell transplantation

Drug: trofosfamide, etoposide

Drug: thiotepa, carboplatin, etoposide

Drug: intraventricular etoposide

Drug: etoposide

2: P-HIT-REZ 2005

Experimental group

Description:

oral chemotherapy with temozolomide, followed by * high dose chemotherapy with temozolomide, thiotepa and autologous stem cell transplantation if patient have achieved a complete remission * maintenance therapy with oral temozolomide or in case of progression with oral trofosfamide, etoposide

Treatment:

Procedure: autologous stem cell transplantation

Drug: temozolomide

Drug: intraventricular etoposide

Drug: temozolomide, thiotepa

3: E-HIT-REZ 2005

Experimental group

Description:

Phase II: oral chemotherapy with temozolomide after progression oral trofosfamide, etoposide

Treatment:

Drug: temozolomide

Drug: trofosfamide, etoposide

Drug: intraventricular etoposide

Intraventricular Etoposide

Experimental group

Description:

Phase II, intraventricular chemotherapy with etoposide

Treatment:

Drug: intraventricular etoposide