Clinical Trial: Irinotecan Hydrochloride and Temozolomide With Temsirolimus or Dinutuximab in Treating Younger Patients With Refractory or Relapsed Neuroblastoma
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Phase II Randomized Trial of Irinotecan/Temozolomide With Temsirolimus (NSC# 683864) or Chimeric 14.18 Antibody (ch14.18) (NSC# 764038) in Children With Refractory, Relapsed or Progressive Neuroblas
Brief Summary: This randomized phase II trial studies how well irinotecan hydrochloride and temozolomide with temsirolimus or dinutuximab work in treating younger patients with neuroblastoma that has returned or does not respond to treatment. Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving irinotecan hydrochloride and temozolomide together with temsirolimus or dinutuximab is more effective in treating neuroblastoma.
Detailed Summary:
PRIMARY OBJECTIVES:
I. To identify whether temsirolimus or ch14.18 (dinutuximab) is the optimal therapeutic agent to consider for further testing in a future Phase III randomized trial for treatment of newly diagnosed high-risk neuroblastoma.
II. To determine the response rate of patients with relapsed, refractory or progressive neuroblastoma following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab) and to compare this with the known response rate of patients treated with irinotecan and temozolomide alone.
SECONDARY OBJECTIVES:
I. To compare the response rates (RR) for patients receiving temsirolimus or ch14.18 (dinutuximab) in combination with irinotecan (irinotecan hydrochloride) and temozolomide.
II. To compare the progression free survival (PFS) and overall survival (OS) rates for patients receiving temsirolimus or ch14.18 (dinutuximab) in combination with irinotecan and temozolomide.
III. To compare the toxicities associated with temsirolimus or ch14.18 (dinutuximab) when combined with irinotecan and temozolomide in patients with refractory, relapsed or progressive neuroblastoma.
IV. To compare the ability to maintain intended dose intensity of all agents when temsirolimus or ch14.18 (dinutuximab) is combined with irinotecan and temozolomide in patients with refractory, relapsed or progressive neuroblastoma.
V. To determine the concordance between tumor responses as defined by standard International Neuroblastoma Response Criteria (INRC) versus response per the revised INRC.
Compared between treatment arms using a Fisher's exact test.
Original Primary Outcome: Proportion of Patients who are Responders [ Time Frame: Four months ]
Current Secondary Outcome:
- Ability to maintain intended treatment with all agents (irinotecan hydrochloride, temozolomide and the experimental agent) without a dose reduction or going off protocol therapy for toxicity [ Time Frame: Up to 3 years ]
- Occurrence of unacceptable toxicities, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 3 years ]
- Overall response rate (complete response, PR, stable disease, progressive disease) according to the INRC [ Time Frame: Up to 3 years ]Compared between treatment arms using a Fisher's exact test.
- Overall survival [ Time Frame: Time of enrollment on the study until the occurrence of the first event or until the time of last contact if no event has occurred, assessed up to 3 years ]Kaplan-Meier curves will be generated, and curves will be compared using a log-rank test.
- Progression-free survival, defined as a relapse, progressive disease, or death attributable to tumor or treatment [ Time Frame: Time of enrollment on the study until the occurrence of the first event or until the time of last contact if no event has occurred, assessed up to 3 years ]Kaplan-Meier curves will be generated, and curves will be compared using a log-rank test.
Original Secondary Outcome:
- Response Rate [ Time Frame: Four months ]Responders are defined patients who achieve better than a Partial Response. Patients with Progressive Disease prior to attaining better than a Partial Response will be considered failures for the analysis of response, and go off protocol therapy. In addition, patients who meet off protocol therapy criteria due to toxicity prior to attaining better than Partial Response will also be considered treatment failures. For a given patient, this primary endpoint is binary (responder, non-responder). Patient's response is to be assessed for determination of the best overall response is after the completion of the first 6 cycles.
- Progression-free survival [ Time Frame: 1 year ]An event is defined as a relapse, progressive disease, or death attributable to tumor or treatment. Time to event for Progression free survival will be calculated from the time of enrollment on the study until the occurrence of the first event or until the time of last contact if no event has occurred. Analysis of overall survival (event = death) will also be performed. Patient's response is to be assessed for determination of the best overall response is after the completion of the first 6 cycles.
- Toxicity [ Time Frame: Four months ]The toxicity endpoint will be defined as the occurrence of unacceptable toxicity per the CTCAE v4.0 toxicity grading scale. Patient's response is to be assessed for determination of the best overall response is after the completion of the first 6 cycles.
- Feasibility [ Time Frame: Four months ]Feasibility will be defined as the ability to maintain intended treatment with all agents (irinotecan, temozolomide and the experimental agent) without a dose reduction or going off protocol therapy for toxicity. Patient's response is to be assessed for determination of the best overall response is after the completion of the first 6 cycles.
Information By: National Cancer Institute (NCI)
Dates:
Date Received: January 9, 2013
Date Started: February 2013
Date Completion:
Last Updated: May 18, 2017
Last Verified: May 2017
