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Unspecified Childhood Solid Tumor, Protocol SpecificPhase 1NCT00880282

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

A Phase 1 study testing cixutumumab, temsirolimus and pharmacological study in people with Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 23 sites in 2 countries.

Completed

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

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
cixutumumab, temsirolimus and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
23 sitesin 2 countries
Study dates
Apr 2009to Oct 2012
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 1 year 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, 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)
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  • 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:
  • 0.6 mg/dL (for patients 1 year of age)
  • 0.8 mg/dL (for patients 2 to 5 years of age)
  • 1 mg/dL (for patients 6 to 9 years of age)
  • 1.2 mg/dL (for patients 10 to 12 years of age)
  • 1.5 mg/dL (males) or 1.4 mg/dL (females) (for patients 13 to 15 years of age)
  • 1.7 mg/dL (males) or 1.4 mg/dL (females) (for patients >= 16 years of age)
  • Bilirubin (sum of conjugated + unconjugated) =< 1.5 x upper limit of normal (ULN) for age
  • Serum albumin >= 2 g/dL
  • Patients with seizure disorder may be enrolled if receiving non-enzyme inducing anticonvulsants and well controlled
  • Prothrombin time (PT) and international normalized ratio (INR) < 1.2 x ULN
  • 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
  • Serum cholesterol and serum triglyceride levels 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

  • 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
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  • 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
  • Patients must not have had major surgery for 6 weeks prior to enrollment on the study; patients with history of recent minor surgical procedures (vascular catheter placement, bone marrow evaluation, laparoscopic surgery) will be eligible

Trial locations and contacts

23 sites in 2 countries.

23 sites in 2 countries

United States21 sites

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Mark O Hatfield-Warren Grant Magnuson Clinical Center

    Bethesda, Maryland, 20892

  • 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

  • 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 I Study of IMC-A12 (Anti-Insulin-Like Growth Factor-I Receptor Monoclonal Antibody) in Combination With CCI-779 (Temsirolimus) in Pediatric Patients With Recurrent or Refractory Solid Tumors

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of IMC-A12 (anti-insulin growth factor-1 receptor monoclonal antibody) (cixutumumab) administered as an intravenous infusion once weekly in combination with CCI-779 (temsirolimus) administered intravenously once weekly to children with refractory solid tumors.

II. To define and describe the toxicities of IMC-A12 in combination with temsirolimus administered on this schedule.

III. To characterize the pharmacokinetics of IMC-A12 in combination with temsirolimus in children with refractory cancer.

SECONDARY OBJECTIVES:

  1. To preliminarily define the antitumor activity of the combination of IMC-A12 and temsirolimus within the confines of a Phase I study.

II. To assess the biologic activity of IMC-A12 by assessing: changes in insulin-like growth factor receptor (IGFR) expression and phosphorylation and insulin-receptor expression and phosphorylation in peripheral blood mononuclear cells (PBMNC).

III. To assess the biological activity of temsirolimus by measuring levels of phosphorylated (phosphor)-ribosomal protein S6 kinase, 70kDa, polypeptide 1 (S6K1), phosphor-protein kinase B (AKT), phosphor-eukaryotic translation initiation factor 4 gamma, 1 (eIF4G) in PBMNC.

IV. To assess the incidence of IGFR expression as well as mechanistic target of rapamycin (mTOR) pathway activation in recurrent or refractory solid tumors of childhood.

OUTLINE:

Patients receive cixutumumab intravenously (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.

After completion of study therapy, patients are followed up periodically.

Being tested
cixutumumab, temsirolimus, pharmacological study, laboratory biomarker analysis

What participants receive

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

  • cixutumumabBiological

    Also called anti-IGF-1R recombinant monoclonal antibody IMC-A12, IMC-A12

    Given IV

  • temsirolimusDrug

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

    Given IV

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00880282
Study groupRoleWhat they receive
Treatment (cixutumumab, temsirolimus)ExperimentalPatients 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.
Receives: Biological: cixutumumab; Drug: temsirolimus; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

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

  1. 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

    Measured: 28 days

  2. Toxicities as assessed by the NCI CTCAE version 4.0

    Measured: Up to 30 days after the last dose of treatment

  3. 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).

    Measured: 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)

  4. 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).

    Measured: 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)

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

    Reported descriptively.

    Measured: Up to 4 years

  2. Change IGFR and insulin receptor expression

    Summary statistics and descriptive plots will be generated for IGFR expression. The changes will be assessed using paired t-test or Wilcoxon matched pairs signed rank sum test when appropriate.

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

  3. Change in levels of S6K1, AKT, eIF4G, and associated phosphoproteins

    Summary statistics and descriptive plots will be generated. The changes will be assessed using paired t-test or Wilcoxon matched pairs signed rank sum test when appropriate.

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

  4. Incidence of IGFR expression as well as mTOR pathway activation

    Measured: At baseline

Timeline

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

  1. First posted13 Apr 2009 (estimated)
  2. Study startApr 2009
  3. Primary completionOct 2012

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
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00880282
Sponsor's protocol ID
NCI-2011-01910
Other IDs
NCI-2011-01910, COG-ADVL0813, CDR0000639150, ADVL0813, ADVL0813, U01CA097452
Status last verified
Apr 2013
First submitted
10 Apr 2009
Last updated
29 Apr 2014
Results posted
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing cixutumumab, temsirolimus and pharmacological study in people with Unspecified Childhood Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 23 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 27 inclusion and 16 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 29 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 23 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?

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 (time frame: 28 days). The study lists 4 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 NCT00880282.

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 29 Apr 2014.

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