Cixutumumab and Temsirolimus in Treating Younger Patients With Solid Tumors That Have Recurred or Not Responded to Treatment

NCT00880282 | Completed Phase 1

• 5 other identifiers: NCI-2011-01910COG-ADVL0813CDR0000639150ADVL0813U01CA097452
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 23

Brief Summary

This phase I trial is studying the side effects and best dose of cixutumumab when given together with temsirolimus in treating younger patients with solid tumors that have recurred or not responded to treatment. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Unspecified Childhood Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (4)

• Maximum-tolerated dose and recommended phase II dose based on the incidence of dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

  28 days

• Toxicities as assessed by the NCI CTCAE version 4.0

  Up to 30 days after the last dose of treatment

• Pharmacokinetics (PK) of cixutumumab

  The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  At end of infusion, at 1, 3, 6, and 24 hours, days 1, 4, 8, 15, 22, and 28 (of course 1), and days 15 and 28 (of course 2)

• Pharmacokinetics of temsirolimus

  The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

  At end of infusion, at 15 and 30 minutes, at 1, 3, 6, and 24 hours, days 1, 4, 7, and 28 (of course 1), and days 15 and 28 (course 2)

Secondary Outcomes (4)

• Disease response according to Response Evaluation Criteria in Solid Tumors (RECIST)

  Up to 4 years

• Change IGFR and insulin receptor expression

  From baseline to up to 28 days (of course 1)

• Change in levels of S6K1, AKT, eIF4G, and associated phosphoproteins

  From baseline to up to 28 days (of course 1)

• Incidence of IGFR expression as well as mTOR pathway activation

  At baseline

Study Arms (1)

Treatment (cixutumumab, temsirolimus)

EXPERIMENTAL

Patients receive cixutumumab IV over 60 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 25 courses in the absence of disease progression or unacceptable toxicity.

Biological: cixutumumab; Drug: temsirolimus; Other: pharmacological study; Other: laboratory biomarker analysis

Interventions

cixutumumab BIOLOGICAL

Given IV

Also known as: anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A12

Treatment (cixutumumab, temsirolimus)

temsirolimus DRUG

Given IV

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

Treatment (cixutumumab, temsirolimus)

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (cixutumumab, temsirolimus)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (cixutumumab, temsirolimus)

Eligibility Criteria

• Age: 1 Year - 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, optic pathway gliomas, or patients with pineal tumors and elevations of serum or cerebrospinal fluid (CSF) alpha-fetoprotein or beta-human chorionic gonadotropin (HCG); slides or tissue blocks from either initial diagnosis or relapse must be available for central review
• 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 clinically 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 chemotherapy, immunotherapy, or radiotherapy prior to entering this study
• Myelosuppressive chemotherapy: must not have received within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)
• Hematopoietic growth factors: at least 7 days since the completion of therapy with a growth factor that supports platelet or white cell number or function
• Biologic (anti-neoplastic agent): at least 7 days since the completion of therapy with a biologic agent; at least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody; 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
• Radiation therapy (XRT): \>= 2 wks for local palliative XRT (small port); \>= 3 months must have elapsed if prior total-body irradiation (TBI), craniospinal XRT or if \>= 50% radiation of pelvis; \>= 6 wks must have elapsed if other substantial bone marrow (BM) radiation
• Stem cell transplant or rescue: no evidence of active graft vs. host disease and \>= 2 months must have elapsed since transplant
• Peripheral absolute neutrophil count (ANC) \>= 1000/mm\^3
• Platelet count \>= 100,000/mm\^3 (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
• Hemoglobin \>= 8.0 g/dL (may receive red blood cell \[RBC\] transfusions)
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 OR a serum creatinine based on age/gender as follows:
• mg/dL (for patients 1 year of age)

You may not qualify if:

• 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
• 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 for the duration of the study and for 3 months after the last dose of IMC-A12.
• Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the 7 days prior to enrollment are not eligible
• Patients who are currently receiving another investigational drug are not eligible
• Patients who are currently receiving other anticancer agents are not eligible
• Patients receiving insulin or growth hormone therapy are not eligible
• Patients must not be receiving enzyme-inducing anticonvulsants
• 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 wort
• Patients receiving warfarin for the purpose of systemic anticoagulation are not eligible; use of low-dose warfarin for maintaining patency of central venous catheters is allowed
• Patients who have an uncontrolled infection are not eligible
• Patients with known type I or type II diabetes mellitus are not eligible
• Patients with known bone marrow involvement 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 who have received prior monoclonal antibody therapy targeting IGF-1R or temsirolimus are not eligible
• Patients with history of allergic reactions attributed to compounds of similar chemical; or biologic composition to IMC-A12 or temsirolimus are not eligible

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (23)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Childrens Hospital of Orange County

Orange, California, 92868-3874, 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

cixutumumab; temsirolimus; Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Maryam Fouladi

  Children's Oncology Group

  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: April 10, 2009
• First Posted: April 13, 2009
• Study Start: April 1, 2009
• Primary Completion: October 1, 2012
• Last Updated: April 29, 2014

Record last verified: 2013-04

Locations

US (21); CA (2)