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Unspecified Childhood Solid Tumor, Protocol SpecificPhase 1NCT01141244

Temsirolimus, Irinotecan Hydrochloride, and Temozolomide in Treating Younger Patients With Relapsed or Refractory Solid Tumors

A Phase 1 study testing temsirolimus, temozolomide and irinotecan hydrochloride in people with Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 25 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase I trial studies the side effects and the best dose of temsirolimus when given together with irinotecan hydrochloride and temozolomide in treating younger patients with recurrent or refractory solid tumors. Read more about this study

Who is it for?
Ages 2 to 21 years
What is being tested?
temsirolimus, temozolomide and irinotecan hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
25 sitesin 2 countries
Study dates
Jun 2010to Nov 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 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, patients with optic pathway gliomas, and patients with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein or beta-human chorionic gonadotropin (HCG)
  • Patients must have either measurable or evaluable disease
  • Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life
  • Karnofsky >= 50% for patients > 16 years of age and Lansky >= 50 for patients =< 16 years of age; Note: neurologic deficits in patients with central nervous system (CNS) tumors must have been relatively stable for a minimum of 1 week prior to study enrollment; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy;
  • Myelosuppressive chemotherapy: patients must not have received myelosuppressive therapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
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  • Hematopoietic growth factors: at least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • Biologic (anti-neoplastic agent): at least 7 days after the last of a biologic agent that is not a monoclonal antibody and enrollment on this study; for agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur; the duration of this interval must be discussed with the study chair
  • Immunotherapy: at least 6 weeks since the completion of any type of immunotherapy, e.g. tumor vaccines
  • Monoclonal antibodies: at least 3 half-lives must have elapsed after treatment with a monoclonal antibody and enrollment on this study
  • Radiation therapy (XRT): >= 2 weeks must have elapsed for local palliative XRT (small port) and enrollment on study; at least 24 weeks must have elapsed since radiation if prior total body irradiation (TBI), craniospinal XRT or if radiation to >= 50% radiation of pelvis has been administered; >= 6 weeks must have elapsed if the patient has received other substantial bone marrow (BM) radiation
  • Stem Cell Infusion without TBI: the patient must have no evidence of active graft versus (vs.) host disease, and >= 12 weeks must have elapsed since transplant or stem cell infusion and enrollment on this study
  • Prior treatment with irinotecan, temozolomide, or temsirolimus: patients previously treated with any of these drugs as single agents will be eligible for this study; patients previously treated with two of the three drugs (including irinotecan + temozolomide) will also be eligible, however patients previously treated with all three agents in combination will not be eligible
  • Peripheral absolute neutrophil count (ANC) >= 1,000/mm^3
  • Platelet count >= 100,000/mm^3 (transfusion independent defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min OR a serum creatinine based on age and/or gender as follows:
  • 0.6 mg/dL (1 to < 2 years of age)
  • 0.8 mg/dL (2 to < 6 years of age)
  • 1.0 mg/dL (6 to < 10 years of age)
  • 1.2 mg/dL (10 to < 13 years of age)
  • 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • 1.7 mg/dL (male) or 1.4 mg/dL (female) (>= 16 years of age)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 times upper limit of normal (ULN)
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 110 U/L; for the purpose of this study, the ULN for SGPT is 45 U/L
  • Serum albumin > 2 g/dL
  • Prothrombin time (PT) < 1.2 times ULN
  • Serum triglyceride level =< 300 mg/dL
  • Serum cholesterol =< 300 mg/dL
  • Random or fasting blood glucose within the upper normal limits for age; if the initial blood glucose is a random sample that is outside of the normal limits, then a follow-up fasting blood glucose can be obtained and must be within the upper normal limits for age
  • Normal pulmonary function tests, including diffusion capacity of carbon monoxide (DLCO), if there is clinical indication for determination (e.g., dyspnea at rest, known requirement for supplemental oxygen); for patients who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT required
  • Patients with seizure disorder may be enrolled if on non-enzyme inducing anticonvulsants and if seizures are well controlled
  • Nervous system disorders (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0 [v4]) resulting from prior therapy must be =< grade 2
  • All patients and/or their parents or legal guardians must sign a written informed consent; assent, when appropriate, will be obtained according to institutional guidelines

Who cannot join

  • Pregnant or breast-feeding women will not be entered on this study; pregnancy tests must be obtained in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
  • Patients receiving chronic systemic corticosteroids are not eligible; patients must have been off systemic corticosteroids for 7 days prior to enrollment
  • Patients who are currently receiving another investigational drug are not eligible
  • Patients who are currently receiving other anti-cancer agents are not eligible
  • Patients who are currently receiving enzyme inducing anticonvulsants are not eligible
  • Patients must not be receiving any of the following potent Cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. John's worth
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  • Patients who are currently receiving therapeutic anticoagulants (including aspirin, low molecular weight heparin, and others) are not eligible
  • Patients who are currently receiving angiotensin-converting enzyme (ACE) inhibitors are not eligible
  • Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial.
  • Patients who have an uncontrolled infection are not eligible
  • Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible
  • Patients with history of allergic reactions attributed to compounds of similar composition to irinotecan hydrochloride, temozolomide, or temsirolimus are not eligible
  • Patients must not have had major surgery for 6 weeks prior to enrollment on study; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery and the like) will be eligible

Trial locations and contacts

25 sites in 2 countries.

25 sites in 2 countries

United States23 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mark O Hatfield-Warren Grant Magnuson Clinical Center

    Bethesda, Maryland, 20892

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60614

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University Medical Center

    Indianapolis, Indiana, 46202

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Midwest Children's Cancer Center

    Milwaukee, Wisconsin, 53226

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • Columbia University Medical Center

    New York, New York, 10032

  • Childrens Hospital of Orange County

    Orange, California, 92868-3874

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of California San Francisco Medical Center-Parnassus

    San Francisco, California, 94143

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Canada2 sites

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

Other trials in Canada

About this study

Official title: A Phase 1 Study of Temsirolimus in Combination With Irinotecan and Temozolomide in Children, Adolescents, and Young Adults With Relapsed or Refractory Solid Tumors

This phase I trial studies the side effects and the best dose of temsirolimus when given together with irinotecan hydrochloride and temozolomide in treating younger patients with recurrent or refractory solid tumors. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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 or by stopping them from dividing. Giving temsirolimus with combination chemotherapy may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) or recommended Phase 2 dose and schedule of temsirolimus administered in combination with irinotecan (irinotecan hydrochloride) and temozolomide every three weeks to children with recurrent or refractory solid tumors.

II. To define and describe the toxicities of the combination of temsirolimus, irinotecan and temozolomide administered on this schedule.

SECONDARY OBJECTIVES:

  1. To preliminarily define the antitumor activity of the combination of temsirolimus, irinotecan, and temozolomide within the confines of a Phase 1 study.

II. To collect preliminary data regarding the biologic effects of temsirolimus on proteins involved in signaling pathways of interest in pediatric solid tumors.

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

Patients receive temsirolimus intravenously (IV) over 30 minutes on days 1 and 8 or on days 1, 8, and 15 and temozolomide orally (PO) and irinotecan hydrochloride PO on days 1-5. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up for 30 days.

Being tested
temsirolimus, temozolomide, irinotecan hydrochloride, laboratory biomarker analysis

What participants receive

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

  • temsirolimusDrug

    Also called CCI-779, cell cycle inhibitor 779, Torisel

    Given IV

  • temozolomideDrug

    Also called SCH 52365, Temodal, Temodar, TMZ

    Given orally

  • irinotecan hydrochlorideDrug

    Also called Campto, Camptosar, CPT-11, irinotecan

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01141244
Study groupRoleWhat they receive
Treatment (temsirolimus, irinotecan, temozolomide)ExperimentalPatients receive temsirolimus IV over 30 minutes on days 1 and 8 or on days 1, 8, and 15 and temozolomide PO and irinotecan hydrochloride PO on days 1-5. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Receives: Drug: temsirolimus; Drug: temozolomide; Drug: irinotecan hydrochloride; Other: laboratory biomarker analysis

What is being measured

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

  1. MTD of temsirolimus defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) as graded by the National Cancer Institute (NCI) CTCAE version 4.0

    Measured: Up to 21 days

  2. Incidence of adverse events as graded by NCI CTCAE version 4.0

    A descriptive summary of all toxicities will be reported.

    Measured: Up to 30 days post-treatment

Secondary outcomes (1)

  1. Disease response (complete or partial response, stable disease, or progressive disease) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST)

    Measured: Up to 30 days post-treatment

Timeline

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

  1. First posted10 Jun 2010 (estimated)
  2. Study startJun 2010
  3. Primary completionNov 2013

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
72 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01141244
Sponsor's protocol ID
NCI-2011-02044
Other IDs
NCI-2011-02044, COG-ADVL0918, CDR0000674293, ADVL0918, ADVL0918, U01CA097452
Status last verified
Dec 2013
First submitted
9 Jun 2010
Last updated
10 Apr 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing temsirolimus, temozolomide and irinotecan hydrochloride in people with Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 25 sites in 2 countries.

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

Who may be eligible to take part?

The sponsor lists 33 inclusion and 13 exclusion criteria. 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: finished, as of the sponsor's last update on 10 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Canada. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

MTD of temsirolimus defined as the maximum dose at which fewer than one-third of patients experience dose-limiting toxicity (DLT) as graded by the National Cancer Institute (NCI) CTCAE version 4.0 (time frame: Up to 21 days). The study lists 2 primary outcomes in all. 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 NCT01141244.

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 10 Apr 2014; AzTrials last refreshed its copy on 8 Nov 2026.

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