Temsirolimus and Valproic Acid in Treating Young Patients With Relapsed Neuroblastoma, Bone Sarcoma, or Soft Tissue Sarcoma

NCT01204450 | Terminated Phase 1 DMC

• 3 other identifiers: LCCC 0901P30CA016086CDR0000665319
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

Brief Summary

RATIONALE: Drugs such as temsirolimus and valproic acid may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Valproic acid may also stop the growth of solid tumors by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and the best dose of temsirolimus when given together with valproic acid in treating young patients with relapsed neuroblastoma, bone sarcoma, or soft tissue sarcoma.

Conditions

Brain and Central Nervous System Tumors; Neuroblastoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

recurrent childhood brain tumor; recurrent childhood rhabdomyosarcoma; recurrent childhood soft tissue sarcoma; recurrent childhood supratentorial primitive neuroectodermal tumor; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent neuroblastoma; recurrent osteosarcoma; unspecified childhood solid tumor, protocol specific

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of temsirolimus in combination with valproic acid

  The planned starting dose of Temsirolimus is 60mg/M2. The traditional 3+3 design will be used, where the MTD is defined as the dose with the probability of a DLT of 0.20

  4 weeks

Secondary Outcomes (3)

• Objective response rate

  every 12 weeks

• Progression-free survival

  3 years

• Temsirolimus pharmakokinetic parameters (Maximum plasma concentration)

  doses 1 and 5

Study Arms (1)

Single Arm Temsirolimus + Valproic Acid

OTHER

Drug: temsirolimus 60-230mg/m2 weekly during each 28 day course, for up to 12 courses Drug: valproic acid (VPA) All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses

Drug: Temsirolimus; Drug: Valproic Acid

Interventions

Temsirolimus DRUG

60-230mg/m2 weekly during each 28 day course, for up to 12 courses

Also known as: Torisel

Single Arm Temsirolimus + Valproic Acid

Valproic Acid DRUG

All patients will be given oral VPA (5 mg/kg, 3 times a day for each 28 day course, up to 12 courses

Also known as: VPA

Single Arm Temsirolimus + Valproic Acid

Eligibility Criteria

• Age: 2 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

DISEASE CHARACTERISTICS: * Histologically confirmed malignant solid tumor at original diagnosis, including the following: * Neuroblastoma * Bone sarcomas (primary neuroectodermal tumors/ Ewing sarcoma (PNET/ES), osteosarcoma) * Soft tissue sarcomas (rhabdosarcoma and related tumors) * Histologically confirmed of relapsed disease is highly recommended but not mandatory * Measurable disease according to RECIST * Refractory or progressive disease after ≥ 1 and ≤ 4 prior chemotherapy regimens * Patients with neuroblastoma, PNET/ES, or rhabdosarcoma must have failed a cyclophosphamide/topotecan-containing regimen * Stem cell transplantation, including preparative regimen and post-transplant immunotherapy, is considered to be 1 regimen PATIENT CHARACTERISTICS: * Karnofsky performance status (PS) 50-100% (or Lansky PS 50-100%) * Life expectancy ≥ 8 weeks * ANC ≥ 750/mm\^3 * Platelet count ≥ 75,000/mm\^3 (transfusion independent) * Hemoglobin 8.0 g/dL (may receive RBC transfusions) * Patients with tumor metastatic to bone marrow are allowed to receive transfusions to maintain hemoglobin and platelet counts * Serum creatinine normal * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) OR direct bilirubin \< 1.0 mg/dL (if total bilirubin \> 2.0 mg/dL) * ALT \< 5 times ULN * Negative pregnancy test * Not pregnant or nursing * Fertile patients must use effective contraception * Families must be able to give consent in English or Spanish * No allergy to H1 antihistamines PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 2 weeks since prior chemotherapy, immunotherapy, or radiotherapy and recovered * No concurrent anticonvulsants, including valproic acid * No concurrent strong inducers or inhibitors of CYP3A4, including grapefruit juice

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Carolina Healthcare System

Charlotte, North Carolina, United States

Location

MeSH Terms

Conditions

Central Nervous System Neoplasms; Neuroblastoma; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Osteosarcoma

Interventions

temsirolimus; Valproic Acid

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue

Intervention Hierarchy (Ancestors)

Pentanoic Acids; Valerates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Julie Blatt, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2010
• First Posted: September 17, 2010
• Study Start: November 1, 2009
• Primary Completion: November 1, 2012
• Study Completion: March 1, 2013
• Last Updated: December 23, 2016

Record last verified: 2016-12

Locations

US (2)