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CompletedNCT01141244Updated Apr 10, 2014

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

A Phase 1 interventional study of temsirolimus and temozolomide in Unspecified Childhood Solid Tumor, Protocol Specific, sponsored by National Cancer Institute (NCI). Completed at 25 sites in 2 countries. Open to participants aged 2 Years to 21 Years. Per ClinicalTrials.gov, last updated 2014-04-10.

Sponsored by National Cancer Institute (NCI) · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
72
Allocation
Not applicable
Ages
2 Years to 21 Years
Sex
All
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Study 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. 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:

I. 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:

I. 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.

02

Conditions studied

  • Unspecified Childhood Solid Tumor, Protocol Specific

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03

In context

Neoplasms

9,365 studies on the registry are indexed under Neoplasms; 2,489 are open to participants now.

This study's enrollment of 72 is above the median of 50 across 7,253 interventional studies indexed under Neoplasms.

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Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.

Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
2 Years to 21 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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)
    • 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

Exclusion criteria

Exclusion Criteria:

  • 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
  • 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
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
72 participants (actual)

Study arms

  • Experimental
    Treatment (temsirolimus, irinotecan, temozolomide)

    Patients 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.

    Drug: temsirolimus · Drug: temozolomide · Drug: irinotecan hydrochloride · Other: laboratory biomarker analysis

Interventions

  • Drugtemsirolimus

    Given IV

    Also known as: CCI-779, cell cycle inhibitor 779, Torisel

  • Drugtemozolomide

    Given orally

    Also known as: SCH 52365, Temodal, Temodar, TMZ

  • Drugirinotecan hydrochloride

    Given IV

    Also known as: Campto, Camptosar, CPT-11, irinotecan, U-101440E

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  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

    Time frame: 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.

    Time frame: Up to 30 days post-treatment

Secondary outcomes

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

    Time frame: Up to 30 days post-treatment

07

Study locations

25 sites
  • Children's Hospital of Alabama
    Birmingham, Alabama 35233, United States
  • University of Alabama at Birmingham
    Birmingham, Alabama 35294, United States
  • Childrens Hospital of Orange County
    Orange, California 92868-3874, United States
  • University of California San Francisco Medical Center-Parnassus
    San Francisco, California 94143, United States
  • Children's National Medical Center
    Washington, District of Columbia 20010, United States
  • Lurie Children's Hospital-Chicago
    Chicago, Illinois 60614, United States
  • Indiana University Medical Center
    Indianapolis, Indiana 46202, United States
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • Mark O Hatfield-Warren Grant Magnuson Clinical Center
    Bethesda, Maryland 20892, United States
  • Dana-Farber Cancer Institute
    Boston, Massachusetts 02115, United States
  • C S Mott Children's Hospital
    Ann Arbor, Michigan 48109, United States
  • University of Minnesota Medical Center-Fairview
    Minneapolis, Minnesota 55455, United States
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • Columbia University Medical Center
    New York, New York 10032, United States
  • Cincinnati Children's Hospital Medical Center
    Cincinnati, Ohio 45229, United States
  • Oregon Health and Science University
    Portland, Oregon 97239, United States
  • Children's Hospital of Philadelphia
    Philadelphia, Pennsylvania 19104, United States
  • Children's Hospital of Pittsburgh of UPMC
    Pittsburgh, Pennsylvania 15224, United States
  • St. Jude Children's Research Hospital
    Memphis, Tennessee 38105, United States
  • University of Texas Southwestern Medical Center
    Dallas, Texas 75390, United States
  • Baylor College of Medicine
    Houston, Texas 77030, United States
  • Seattle Children's Hospital
    Seattle, Washington 98105, United States
  • Midwest Children's Cancer Center
    Milwaukee, Wisconsin 53226, United States
  • Hospital for Sick Children
    Toronto, Ontario M5G 1X8, Canada
  • Centre Hospitalier Universitaire Sainte-Justine
    Montreal, Quebec H3T 1C5, Canada
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 10, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT01141244
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Jun 10, 2010
Start date
Jun 2010
Primary completion
Nov 2013
Last update
Apr 10, 2014

Study contacts

Rochelle Bagatell
principal investigator · COG Phase I Consortium
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Dec 2013. You cannot join it, but the record below documents what was studied.

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