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Brain and Central Nervous System TumorsPhase 1NCT01204450

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

A Phase 1 study testing Temsirolimus and Valproic Acid in people with Brain and Central Nervous System Tumors and Neuroblastoma, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 18 years
What is being tested?
Temsirolimus and Valproic Acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
2 sitesUnited States
Study dates
Nov 2009to Mar 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

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

    Chapel Hill, North Carolina, 27599-7295

  • Carolina Healthcare System

    Charlotte, North Carolina

Other trials in United States

About this study

Official title: A Multi-center Phase I Trial of Temsirolimus in Combination With Valproic Acid in Children and Adolescents With Multiply Relapsed Pediatric Solid Tumors

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.

Read the detailed description

OBJECTIVES:

Primary

  • To identify the maximum-tolerated dose of temsirolimus in combination with valproic acid in highly pretreated pediatric patients with refractory solid tumors.

Secondary

  • To estimate the objective response rate in patients treated with this regimen.
  • To estimate the progression-free survival of patients treated with this regimen.
  • To explore the association between tumor IGF-IR, mTOR expression, HDAC, autophagy biomarkers, and sera levels of temsirolimus, valproate, and VEGF-A with toxicity and disease response.
  • To evaluate the ability of selected member divisions of a newly developed North Carolina-based pediatric oncology consortium to cooperate in clinical trials.

OUTLINE: This a multicenter, dose-escalation study of temsirolimus.

Patients receive temsirolimus IV over 30-60 minutes on days 1, 8, 15, and 22 and oral valproic acid* 3 times daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Blood samples are collected at baseline and periodically during study for pharmacokinetic and VEGF-A studies. Tumor tissue samples from archived biopsy are also analyzed for IGF-IR, mTOR expression, HDAC, and autophagy biomarkers.

After completion of study therapy, patients are followed every 3 months for 1 year, every 4 months for 2 years, and then every 6 months for 2 years.

NOTE: * Doses of valproic acid are titrated beginning 3-7 days prior to starting temsirolimus to achieve plasma levels of 75-100 µg/mL.

Being tested
Temsirolimus, Valproic Acid
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
Medical subject headings
Central Nervous System Neoplasms, Neuroblastoma, Sarcoma, Neuroectodermal Tumors, Primitive, Peripheral, Osteosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TemsirolimusDrug

    Also called Torisel

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

  • Valproic AcidDrug

    Also called VPA

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

Study groups in NCT01204450
Study groupRoleWhat they receive
Single Arm Temsirolimus + Valproic AcidOtherDrug: 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
Receives: Drug: Temsirolimus; Drug: Valproic Acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 4 weeks

Secondary outcomes (3)

  1. Objective response rate

    Each patient will be classified according to their "best response". Best response is determined from the sequence of the objective statuses as described in RECIST 1.1

    Measured: every 12 weeks

  2. Progression-free survival

    If the patient's disease has not progressed at the time protocol-directed therapy is complete, any tumor assessments available during the follow-up period (up to 3 years) will be evaluated using RECSIT 1.1

    Measured: 3 years

  3. Temsirolimus pharmakokinetic parameters (Maximum plasma concentration)

    Blood will be drawn prior to, 30 minutes, 1hr, 2hr, 5hr, 24hr after completion of doses 1 and 5. Levels of Temsirolimus will be measured using validated liquid chromatography and tandem mass spectroscopic methods

    Measured: doses 1 and 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2010 (estimated)
  2. Study startNov 2009
  3. Primary completionNov 2012
  4. Study completionMar 2013

Why it stopped: Funding has become unavailable

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01204450
Sponsor's protocol ID
LCCC 0901
Other IDs
P30CA016086, CDR0000665319
Status last verified
Dec 2016
First submitted
16 Sep 2010
Last updated
23 Dec 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Temsirolimus and Valproic Acid in people with Brain and Central Nervous System Tumors and Neuroblastoma, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 23 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Funding has become unavailable). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of temsirolimus in combination with valproic acid (time frame: 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01204450.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2016.

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