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Childhood Alveolar Soft Part SarcomaPhase 2NCT01614795

Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma

A Phase 2 study testing Cixutumumab, Laboratory Biomarker Analysis and Temsirolimus in people with Childhood Alveolar Soft Part Sarcoma and Childhood Angiosarcoma, run by National Cancer Institute (NCI) at 76 sites in 2 countries.

Completed

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

Official record
Search all trials

Trial summary

This phase II trial studies how well cixutumumab and temsirolimus work in treating patients with recurrent or refractory sarcoma. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Read more about this study

Who is it for?
Ages 1 year to 30 years
What is being tested?
Cixutumumab, Laboratory Biomarker Analysis and Temsirolimus
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
76 sitesin 2 countries
Study dates
18 Jun 2012to 1 Apr 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients with any of the following tumors who have experienced relapse following front-line therapy, or who are refractory to front-line therapy, are eligible:
  • Osteosarcoma
  • Ewing sarcoma/peripheral primitive neuroectodermal tumor (PNET)
  • Rhabdomyosarcoma
  • Non-rhabdomyosarcoma soft tissue sarcoma
  • Patients must have had histologic verification of malignancy at original diagnosis or relapse
Show all 67Show fewer
  • All patients are required to submit archival tumor samples for immunohistochemical analysis (either paraffin-embedded tumor blocks or unstained slides)
  • Tissue samples collected at original diagnosis or at relapse or at any subsequent resections or biopsies should be available and ready for shipment to the Biopathology Center (BPC) at time of study enrollment; the samples are required even if tissue samples have previously been sent to the BPC for other purposes or studies; blocks or slides should be shipped to the BPC within 7 days of study enrollment
  • Patients must have radiographically measurable disease
  • Measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)
  • The following do not qualify as measurable disease:
  • Malignant fluid collections (e.g., ascites, pleural effusions)
  • Bone marrow infiltration
  • Lesions only detected by nuclear medicine studies (e.g., bone, gallium, or positron emission tomography [PET] scans)
  • Elevated tumor markers in plasma or cerebrospinal fluid(CSF)
  • Previously radiated lesions that have not demonstrated clear progression post radiation
  • Leptomeningeal lesions that do not meet the measurements noted above
  • 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
  • Patients with known central nervous system metastases are excluded unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months
  • Patients must have a Lansky or Karnofsky performance status score of ? 50%, corresponding to Eastern Cooperative Oncology Group (ECOG) categories 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients ? 16 years of age
  • 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
  • For patients with solid tumors without bone marrow involvement:
  • Peripheral absolute neutrophil count (ANC) ? 1,000/?L
  • Platelet count ? 100,000/?L (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)
  • For patients with solid tumors and known bone marrow metastatic disease:
  • ANC ? 750/?L
  • Platelet count ? 50,000/?L (may receive platelet transfusions)
  • Hemoglobin ? 8.0 g/dL (may receive RBC transfusions)
  • For patients with known bone marrow metastatic disease, transfusions are permitted to meet both platelet and hemoglobin criteria; patients must not be known to be refractory to red blood cell or platelet transfusions
  • Creatinine clearance or radioisotope GFR ? 70 mL/min OR a serum creatinine based on age/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 (males) or 1.4 mg/dL (females) (13 to < 16 years of age)
  • 1.7 mg/dL (males) or 1.4 mg/dL (females) ( ? 16 years of age)
  • Total bilirubin ? 1.5 times upper limit of normal (ULN)
  • Serum glutamic pyruvate transaminase(SGPT) (alanine aminotransaminase [ALT]) ? 2.5 times ULN (for the purpose of this study, the ULN for SGPT is 45 U/L)
  • Serum albumin ? 2 g/dL
  • Patients with seizure disorder may be enrolled if receiving non-enzyme-inducing anticonvulsants and well controlled
  • Patients with known type I or type II diabetes mellitus are not eligible
  • Serum glucose values must be within the normal limits for age; if the initial blood glucose is a random sample that is outside normal limits, then a follow-up fasting blood glucose should be obtained and must be within the normal limits for age
  • Serum cholesterol levels must be < grade 2 (< 300 mg/dL), and serum triglyceride levels must be < grade 2 (< 2.5 times ULN)
  • Patients who are pregnant or breast-feeding are not eligible for this study
  • Negative 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 cixutumumab
  • 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
  • See Disease Characteristics
  • There is no limit to the number of prior treatment regimens; however, patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study enrollment
  • Patients must not have received myelosuppressive chemotherapy within 3 weeks of enrollment (6 weeks if prior nitrosourea)
  • At least 7 days must have elapsed since the completion of therapy with a growth factor; at least 14 days must have elapsed after receiving pegfilgrastim
  • At least 7 days must have elapsed since the completion of therapy with a biologic agent; for agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur
  • At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody
  • ? 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); 3 months must have elapsed if 50% radiation of pelvis; 6 weeks must have elapsed if therapeutic doses of metaiodobenzylguanidine(MIBG) or other substantial bone marrow irradiation was given
  • No evidence of active graft-vs-host disease and 2 months must have elapsed since stem cell transplant or rescue
  • Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment (14 days if Neulasta?)
  • 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 anti-cancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy, are not eligible
  • Patients receiving insulin or growth hormone therapy are not eligible
  • Patients who are receiving enzyme-inducing anticonvulsants are not eligible
  • Use of warfarin is not allowed while on study; patients already on warfarin should use alternative anticoagulants while on this study; warfarin must not have been administered within 7 days of starting protocol therapy
  • Patients who have received prior therapy targeting IGF-1R with either monoclonal antibodies or small molecule tyrosine kinase inhibitors are NOT eligible
  • Prior treatment with mTOR inhibitors (e.g., rapamycin, temsirolimus, everolimus, deforolimus) is NOT allowed
  • Patients who have had major surgery within 3 weeks prior to enrollment are not eligible; procedures such as placement of a central vascular catheter or limited tumor biopsy are not considered major surgery

Who cannot join

None listed.

Trial locations and contacts

76 sites in 2 countries.

76 sites in 2 countries

United States74 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87102

  • Children's Healthcare of Atlanta - Egleston

    Atlanta, Georgia, 30322

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Novant Health Presbyterian Medical Center

    Charlotte, North Carolina, 28204

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Palmetto Health Richland

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

    Denver, Colorado, 80218

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Lee Memorial Health System

    Fort Myers, Florida, 33901

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • Saint Vincent Hospital and Health Care Center

    Indianapolis, Indiana, 46260

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic-Jacksonville

    Jacksonville, Florida, 32207

  • The Childrens Mercy Hospital

    Kansas City, Missouri, 64108

  • East Tennessee Childrens Hospital

    Knoxville, Tennessee, 37916

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • University of Arkansas for Medical Sciences

    Little Rock, Arkansas, 72205

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Miller Children's and Women's Hospital Long Beach

    Long Beach, California, 90806

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • Morristown Medical Center

    Morristown, New Jersey, 07960

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520

  • Ochsner Medical Center Jefferson

    New Orleans, Louisiana, 70121

  • Columbia University/Herbert Irving Cancer Center

    New York, New York, 10032

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Children's Hospital and Research Center at Oakland

    Oakland, California, 94609-1809

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • Children's Hospital of Orange County

    Orange, California, 92868

  • Florida Hospital Orlando

    Orlando, Florida, 32803

  • Nemours Children's Clinic - Orlando

    Orlando, Florida, 32806

  • Lucile Packard Children's Hospital Stanford University

    Palo Alto, California, 94304

  • Nemours Children's Clinic - Pensacola

    Pensacola, Florida, 32504

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Virginia Commonwealth University/Massey Cancer Center

    Richmond, Virginia, 23298

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • Memorial University Medical Center

    Savannah, Georgia, 31404

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Providence Sacred Heart Medical Center and Children's Hospital

    Spokane, Washington, 99204

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Johns Hopkins All Children's Hospital

    St. Petersburg, Florida, 33701

  • Stony Brook University Medical Center

    Stony Brook, New York, 11794

  • Overlook Hospital

    Summit, New Jersey, 07902

  • Mary Bridge Children's Hospital and Health Center

    Tacoma, Washington, 98405

  • Scott and White Memorial Hospital

    Temple, Texas, 76508

  • Mercy Children's Hospital

    Toledo, Ohio, 43608

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada2 sites

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Centre Hospitalier Universitaire de Quebec

    Québec, G1V 4G2

Other trials in Canada

About this study

Official title: A Phase II Study of Cixutumumab (IMC-A12) in Combination With Temsirolimus in Pediatric Patients With Recurrent or Refractory Solid Tumors

This phase II trial studies how well cixutumumab and temsirolimus work in treating patients with recurrent or refractory sarcoma. 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. Giving cixutumumab and temsirolimus together may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the objective response rate to the combination of cixutumumab and temsirolimus in patients with relapsed or refractory osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma.

II. To further describe the toxicities (including dose-limiting toxicities) of cixutumumab and temsirolimus administered on this schedule.

SECONDARY OBJECTIVES:

  1. To assess the progression-free survival for patients treated in each disease stratum with this drug combination.

II. To assess the incidence of insulin-like growth factor 1 receptor (IGF-1R), insulin receptor, ERK, RON, and mammalian target of rapamycin (mTOR) pathway activation in archival tumor material, and correlate with response.

III. To evaluate minimal residual disease and IGF-1R tumor cell expression in the blood and bone marrow of Ewing sarcoma patients using flow cytometry.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (osteosarcoma vs Ewing sarcoma/PNET vs rhabdomyosarcoma vs non-rhabdomyosarcoma soft tissue sarcoma).

Patients receive cixutumumab IV over 1 hour 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.

Archived tumor tissue samples from most recent biopsy are collected and analyzed for IGF-1R, insulin receptor, AKT, ERK, mTOR, and S6 kinase pathway activation by immunohistochemistry (IHC) and banked for future correlative studies. Blood and bone marrow samples, from patients with Ewing sarcoma, may be collected at baseline and periodically during treatment for minimal residual disease analysis by flow cytometry.

After completion of study treatment, patients are followed up periodically for 5 years.

Being tested
Cixutumumab, Laboratory Biomarker Analysis, Temsirolimus
Medical subject headings
Hemangiosarcoma, Sarcoma, Fibrosarcoma, Liposarcoma, Neuroectodermal Tumors, Primitive, Peripheral, Osteosarcoma, Rhabdomyosarcoma

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

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • TemsirolimusDrug

    Also called CCI-779, CCI-779 Rapamycin Analog, Cell Cycle Inhibitor 779, Rapamycin Analog

    Given IV

Study groups in NCT01614795
Study groupRoleWhat they receive
Treatment (cixutumumab, temsirolimus)ExperimentalPatients receive cixutumumab IV over 1 hour 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; Other: Laboratory Biomarker Analysis; Drug: Temsirolimus

What is being measured

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

  1. Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST).

    Per Response evaluation criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. Overall Response (OR)= CR+PR. The combination of sufficient activity is considered if the true response rate is 35% or greater.

    Measured: 6 cycles (168 days)

  2. Number of Cycles of Toxicity

    The number of patients-cycles where CTC Version 4 grade 3 or higher increased Alanine aminotransferase was observed

    Measured: Duration of protocol therapy - Up to 25 cycles (700 days)

Secondary outcomes (3)

  1. Progression-free Interval

    Percentage Probability of remaining progression-free 5 years after enrollment estimated by the method of Kaplan and Meier

    Measured: 10 months after enrollment

  2. Expression Levels of IGF-1R, Insulin Receptor, ERK, RON, and mTOR

    Number of patients expressing insulin-like growth factor 1 receptor (IGF-1R), insulin receptor, ERK, RON, and mammalian target of rapamycin (mTOR) at levels 0, 1+, 2+, 3+ by immunohistochemistry.

    Measured: Baseline

  3. Number of Patients With Detectable Bone Marrow Micrometastatic Disease Estimated as the Proportion of Eligible Patients Entered Into the Ewing Sarcoma Stratum Who Have Detectable Tumor Cells in the Marrow at Enrollment

    Measured: Baseline

Timeline

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

  1. First posted8 Jun 2012 (estimated)
  2. Study start18 Jun 2012
  3. Primary completion1 Apr 2014
  4. Study completion1 Apr 2014

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01614795
Sponsor's protocol ID
NCI-2012-01971
Other IDs
NCI-2012-01971, ADVL1221, COG-ADVL1221, CDR0000734871, ADVL1221, ADVL1221, U10CA098543
Status last verified
Nov 2018
First submitted
6 Jun 2012
Last updated
11 Dec 2018

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cixutumumab, Laboratory Biomarker Analysis and Temsirolimus in people with Childhood Alveolar Soft Part Sarcoma and Childhood Angiosarcoma, run by National Cancer Institute (NCI) at 76 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 67 inclusion and 0 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 11 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 76 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Objective Response Rate (PR or CR) by Response Evaluation Criteria in Solid Tumors (RECIST). (time frame: 6 cycles (168 days)). The study lists 2 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 NCT01614795.

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 11 Dec 2018.

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