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

NCT01141244 | Completed Phase 1

• 5 other identifiers: NCI-2011-02044COG-ADVL0918CDR0000674293ADVL0918U01CA097452
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 25

Brief 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.

Conditions

Unspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

• 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

  Up to 21 days

• Incidence of adverse events as graded by NCI CTCAE version 4.0

  A descriptive summary of all toxicities will be reported.

  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)

  Up to 30 days post-treatment

Study Arms (1)

Treatment (temsirolimus, irinotecan, temozolomide)

EXPERIMENTAL

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

temsirolimus DRUG

Given IV

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

Treatment (temsirolimus, irinotecan, temozolomide)

temozolomide DRUG

Given orally

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

Treatment (temsirolimus, irinotecan, temozolomide)

irinotecan hydrochloride DRUG

Given IV

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

Treatment (temsirolimus, irinotecan, temozolomide)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (temsirolimus, irinotecan, temozolomide)

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (25)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868-3874, United States

Location

University of California San Francisco Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60614, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Mark O Hatfield-Warren Grant Magnuson Clinical Center

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Midwest Children's Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

MeSH Terms

Interventions

temsirolimus; Sirolimus; Temozolomide; Irinotecan

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Dacarbazine; Triazenes; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids

Study Officials

• Rochelle Bagatell

  COG Phase I Consortium

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 9, 2010
• First Posted: June 10, 2010
• Study Start: June 1, 2010
• Primary Completion: November 1, 2013
• Last Updated: April 10, 2014

Record last verified: 2013-12

Locations

US (23); CA (2)