Clinical trial NCT00808899
Conditions: Neuroblastoma
Keywords: Neuroblastoma
Sponsor: St. Jude Children's Research Hospital
Start date: 2008-12-01; Completion date: 2009-07-01
Enrollment: 4 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A Phase II study of temsirolimus in combination with standard chemotherapy (irinotecan; cyclophosphamide, doxorubicin and etoposide (CAE); cisplatin and etoposide (HiPE) and topotecan (TPT) followed by and additional six courses of induction chemotherapy and then intensification with autologous hematopoietic stem cell transplantation. The first five courses of induction chemotherapy will also evaluate the feasibility of combining weekly temsirolimus with these standard chemotherapy combinations. This will be followed by 16 months of oral maintenance therapy with eight months of 13-cis-retinoic acid and then eight months of oral topotecan.

Detailed description:
All children will receive fixed doses of intravenous temsirolimus (50 mg/m2 weekly 6 times ) concomitantly with two courses of fixed dosages of irinotecan (20 mg/m2 intravenously daily 5 times ,2 days off, repeated daily 5 times .If these initial dosages are not tolerable then subsequent patients will be given a reduced dosage of temsirolimus (25 mg/m2 weekly 6 times) with 20 mg/m2 of irinotecan.If this dosage combination is not tolerable, the irinotecan dosage will be decreased to 15 mg/m2 .If this dosage combination is not tolerable then further enrollment to the initial six week treatment will be terminated.The second course of irinotecan will begin on day 22 and response will be determined after six weeks (two courses). Resection of primary tumor will be attempted after this initial therapy, whenever possible.

Following initial treatment children will undergo alternating courses of induction chemotherapy with cyclophosphamide, doxorubicin, etoposide, topotecan, and cisplatin (Block 2). The first cohort of 17 patients will receive Block 2 with temsirolimus (50mg/m2) for all three courses, weekly 2 times. If this is not tolerated subsequent patients will receive Block 2 chemotherapy with reduced dosages of temsirolimus (25mg/m2).

Arms: arm 1: Fixed doses of IV temsirolimus concomitantly with two courses of fixed dosages of irinotecan, 2 days off, repeated daily 5 times.If initial dosages are not tolerable, subsequent patients will be given a reduced dosage of temsirolimus with irinotecan.If this dosage combination is not tolerable,irinotecan dosage will be decreased.If this dosage combination is not tolerable.Further enrollment to initial six week treatment will be terminated.Second course of irinotecan will begin on day 22, response will be determined after six weeks. Resection of primary tumor will be attempted after initial therapy.Following initial treatment children will undergo alternating courses of induction chemotherapy with cyclophosphamide,doxorubicin,etoposide,topotecan, and cisplatin.First cohort of 17 patients will receive Block 2 with temsirolimus for all three courses, weekly 2 times.If this is not tolerated subsequent patients will receive Block 2 chemotherapy with reduced dosages of temsirolimus.
Interventions: intervention 1: Temsirolimus intervention 2: Irinotecan intervention 3: Surgical Resection of Primary Tumor intervention 4: Cyclophosphamide intervention 5: Doxorubicin intervention 6: Etoposide intervention 7: Cisplatin intervention 8: Topotecan intervention 9: PBSC intervention 10: Radiation Therapy intervention 11: 13-cis-retinoic acid
Intervention descriptions: intervention 1: Temsirolimus intervention 2: Irinotecan intervention 3: Surgical Resection of Primary Tumor intervention 4: Cyclophosphamide intervention 5: Doxorubicin intervention 6: Etoposide intervention 7: Cisplatin intervention 8: Topotecan intervention 9: Peripheral Blood Stem Cell Harvest intervention 10: Radiation Therapy intervention 11: 13-cis-retinoic acid

Protocol documents: