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

NCT ID: NCT01141244

Last Updated: 2014-04-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-06-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

temsirolimus

Intervention Type DRUG

Given IV

temozolomide

Intervention Type DRUG

Given orally

irinotecan hydrochloride

Intervention Type DRUG

Given IV

laboratory biomarker analysis

Intervention Type OTHER

Correlative studies

Interventions

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temsirolimus

Given IV

Intervention Type DRUG

temozolomide

Given orally

Intervention Type DRUG

irinotecan hydrochloride

Given IV

Intervention Type DRUG

laboratory biomarker analysis

Correlative studies

Intervention Type OTHER

Other Intervention Names

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CCI-779 cell cycle inhibitor 779 Torisel SCH 52365 Temodal Temodar TMZ Campto Camptosar CPT-11 irinotecan U-101440E

Eligibility Criteria

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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

* 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
Minimum Eligible Age

2 Years

Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rochelle Bagatell

Role: PRINCIPAL_INVESTIGATOR

COG Phase I Consortium

Locations

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Children's Hospital of Alabama

Birmingham, Alabama, United States

Site Status

University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

Childrens Hospital of Orange County

Orange, California, United States

Site Status

University of California San Francisco Medical Center-Parnassus

San Francisco, California, United States

Site Status

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

Riley Hospital for Children

Indianapolis, Indiana, United States

Site Status

Mark O Hatfield-Warren Grant Magnuson Clinical Center

Bethesda, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status

Oregon Health and Science University

Portland, Oregon, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Seattle Children's Hospital

Seattle, Washington, United States

Site Status

Midwest Children's Cancer Center

Milwaukee, Wisconsin, United States

Site Status

Hospital for Sick Children

Toronto, Ontario, Canada

Site Status

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

Other Identifiers

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NCI-2011-02044

Identifier Type: REGISTRY

Identifier Source: secondary_id

COG-ADVL0918

Identifier Type: -

Identifier Source: secondary_id

CDR0000674293

Identifier Type: -

Identifier Source: secondary_id

ADVL0918

Identifier Type: OTHER

Identifier Source: secondary_id

ADVL0918

Identifier Type: OTHER

Identifier Source: secondary_id

U01CA097452

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-02044

Identifier Type: -

Identifier Source: org_study_id

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