A Phase 2 Single-Arm Study of Gemcitabine in Combination with Oxaliplatin in Pediatric Patients with Relapsed or Refractory Neuroblastoma or Miscellaneous Solid Non-CNS Tumors

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2005-005219-36-DE
• Date of registration: 28/12/2005
• Prospective Registration: Yes
• Primary sponsor: Eli Lilly and Company Limited
• Public title: A Phase 2 Single-Arm Study of Gemcitabine in Combination with Oxaliplatin in Pediatric Patients with Relapsed or Refractory Neuroblastoma or Miscellaneous Solid Non-CNS Tumors
• Scientific title: A Phase 2 Single-Arm Study of Gemcitabine in Combination with Oxaliplatin in Pediatric Patients with Relapsed or Refractory Neuroblastoma or Miscellaneous Solid Non-CNS Tumors
• Date of first enrolment: 06/03/2006
• Target sample size: 70
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-005219-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Germany, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are eligible to be included in the study only if they meet all of the following criteria:
[1] Histologically proven malignancy (at diagnosis): either neuroblastoma or other non-CNS solid tumors (excluding osteosarcoma).
[2] Measurable primary and/or metastatic disease:
For neuroblastoma measurable disease will be defined by the modified International Neuroblastoma Staging System and International Neuroblastoma Response Criteria (Brodeur et al. 1993).
For miscellaneous solid non-CNS tumors measurable disease will be defined by RECIST (Therasse et al. 2000).
[3] Relapsed or refractory tumors in which standard approaches to treatment have failed.
[4] No more than one salvage therapy for relapsed or refractory disease.
[5] 6 months to <18 years of age.
[6] Lansky play score ?70%, or Eastern Cooperative Oncology Group (ECOG) performance status ?1 (where more appropriate).
[7] Life expectancy ?3 months.
[8] Adequate organ function including the following:

Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ?1.0 ? 109/L, platelets ?100 ? 109/L (in case of bone marrow disease: ?75 ? 109/L), and hemoglobin ?8.0g/dL.

Hepatic: bilirubin ?1.5 times the upper limit of normal (? ULN), aspartate transaminase (AST) and alanine transaminase (ALT) ?2.5 ? ULN (AST, and ALT ?5 ? ULN is acceptable if liver has tumor involvement).

Renal: serum creatinine ?1.5 ? ULN for age, according to local lab value. If serum creatinine >1.5 ? ULN for age, then creatinine clearance (or radioisotope GFR) must be >70 ml/min/1.73 m2.
[9] Must have had their last dose of chemotherapy at least 3 weeks prior to study enrollment (first dose of study treatment); 2 weeks if the prior chemotherapy was single-agent vincristine; 6 weeks if the prior chemotherapy contained nitrosoureas.

Must have had their last dose of radiotherapy at least 4 weeks prior to study enrollment (first dose of study treatment);

Patients must have recovered from the acute toxic effects of all prior therapy before enrollment into the study.

[10] Able to comply with scheduled follow up and with management of toxicity.
[11] All patients with reproductive potential must practice an effective method of birth control while on study. Female patients with childbearing potential must have a negative pregnancy test within 7 days before study treatment.
[12] Written informed consent from patients or from parents or legal guardians for minor patients, according to local law and regulations.

Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients will be excluded from the study if they meet any of the following criteria:
[13] Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
[14] Concurrent administration of any other antitumor therapy.
[15] Have previously completed or withdrawn from this study or any other study investigating gemcitabine or oxaliplatin.
[16] Have a serious concomitant systemic disorder (for example, active infection including HIV, or cardiac disease) that, in the opinion of the investigator, would compromise the patient’s ability to complete the study.
[17] Have symptomatic brain metastases.
[18] re-existing sensory or motor neuropathy >Grade 2 (excluding neuropathy due to disease).
[19] History of allergic reaction to platinum compounds.
[20] Are pregnant or breastfeeding.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Relapsed or Refractory Neuroblastoma or Miscellaneous Solid Non-CNS Tumors

Intervention(s)

Trade Name: Gemzar 200 mg
Product Name: gemcitabine
Product Code: LY188011
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: gemcitabine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Eloxatin 5 mg/ml
Product Name: oxaliplatin
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: oxaliplatin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Trade Name: Gemzar 1g
Product Name: gemcitabine
Product Code: LY188011
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: gemcitabine
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Primary end point(s): objective response rate of the gemcitabine plus oxaliplatin combination in pediatric patients with relapsed or refractory neuroblastoma AND
descriptive analysis of responses in the miscellaneous solid non-CNS cohort

Secondary Objective: The secondary objectives of the study are as follows:
• to characterize the safety and adverse event profile of the combination (including evaluating adverse events by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], Version 3)
• to assess the following time-to-event endpoints:
o duration of response
o time to treatment failure
o time to progressive disease
o overall survival.

Main Objective: The primary objective is to assess the antitumor activity, as measured by objective response rate, of the gemcitabine plus oxaliplatin combination in pediatric patients with neuroblastoma. The antitumor activity of the miscellaneous solid non-CNS tumor cohort will be assessed by describing the responses seen in each tumor type.

Secondary ID(s)

B9E-MC-S378