Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00720174
First received: July 19, 2008
Last updated: September 9, 2014
Last verified: September 2014
  Purpose

This phase I trial is studying the side effects and best dose of cixutumumab given together with doxorubicin hydrochloride and to see how well they work in treating patients with unresectable, locally advanced, or metastatic soft tissue 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. Drugs used in chemotherapy, such as doxorubicin hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving monoclonal antibody cixutumumab together with doxorubicin hydrochloride may kill more tumor cells.


Condition Intervention Phase
Adult Angiosarcoma
Adult Desmoplastic Small Round Cell Tumor
Adult Epithelioid Sarcoma
Adult Extraskeletal Chondrosarcoma
Adult Extraskeletal Osteosarcoma
Adult Fibrosarcoma
Adult Leiomyosarcoma
Adult Liposarcoma
Adult Malignant Fibrous Histiocytoma of Bone
Adult Malignant Hemangiopericytoma
Adult Malignant Mesenchymoma
Adult Neurofibrosarcoma
Adult Rhabdomyosarcoma
Adult Synovial Sarcoma
Childhood Angiosarcoma
Childhood Desmoplastic Small Round Cell Tumor
Childhood Epithelioid Sarcoma
Childhood Fibrosarcoma
Childhood Leiomyosarcoma
Childhood Liposarcoma
Childhood Malignant Hemangiopericytoma
Childhood Malignant Mesenchymoma
Childhood Neurofibrosarcoma
Childhood Synovial Sarcoma
Dermatofibrosarcoma Protuberans
Metastatic Childhood Soft Tissue Sarcoma
Mixed Childhood Rhabdomyosarcoma
Pleomorphic Childhood Rhabdomyosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Previously Untreated Childhood Rhabdomyosarcoma
Recurrent Adult Soft Tissue Sarcoma
Recurrent Childhood Rhabdomyosarcoma
Recurrent Childhood Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Biological: cixutumumab
Drug: doxorubicin hydrochloride
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximally tolerated dose (MTD) of cixitumumab when administered in a combination regimen with fixed dose doxorubicin hydrochloride, in patients with locally advanced or metastatic soft tissue sarcoma [ Time Frame: Up to 2 courses of treatment ] [ Designated as safety issue: Yes ]
    The MTD is defined as the dose of Cixitumumab that induces dose-limiting toxicity (DLT) in no more than 20% of patients.


Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: Until documented disease progression or death or loss-to-follow-up, assessed up to 6 months ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method Kaplan and Meier. With point-wise estimates for the 3 and 6-month progression-free survival proportions reported with 95% confidence intervals using Greenwood's formula for calculation of the variance.

  • Overall survival [ Time Frame: Until death due to any cause, or loss to follow-up, assessed up to 6 months ] [ Designated as safety issue: No ]
    Will be estimated using the product-limit method Kaplan and Meier. With point-wise estimates for the 3 and 6-month survival proportions reported with 95% confidence intervals using Greenwood's formula for calculation of the variance.

  • Changes in cardiac function as measured by MUGA scans of the left ventricular ejection fraction [ Time Frame: Baseline to 6 courses of treatment ] [ Designated as safety issue: No ]
  • Confirmed response rate (CR + PR) for comparison with doxorubicin treatment in similar historical patient populations [ Time Frame: Up to 6 months ] [ Designated as safety issue: No ]
    The mean response probability with 90% credible interval will be reported for those patients treated at the dose of cixitumumab found to be the MTD.


Enrollment: 50
Study Start Date: June 2008
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cixutumumab and doxorubicin hydrochloride)
Patients receive cixutumumab IV over 1 hour on days 1, 8, and 15 and doxorubicin hydrochloride IV continuously over 44-52 hours beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue to receive cixutumumab in the absence of disease progression or unacceptable toxicity.
Biological: cixutumumab
Given IV
Other Names:
  • anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • IMC-A12
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To collect safety data about the combination of doxorubicin and Cixitumumab and determine if they can be combined with acceptable toxicity at full doses.

SECONDARY OBJECTIVES:

I. To assess the confirmed response rate (CR + PR as defined by RECIST) of patients with locally advanced or metastatic soft tissue sarcoma when treated with combination doxorubicin and Cixitumumab II. To assess the 3 and 6 month progression free survival rate of patients treated with doxorubicin and Cixitumumab.

III. To assess the progression free survival and overall survival of patients treated with doxorubicin and Cixitumumab.

IV. To evaluate changes in left ventricular ejection fraction assessed by MUGA scan after 2, 4 and 6 cycles of therapy compared to baseline.

OUTLINE: This is a multicenter, dose-escalation study of anti-IGF-1R recombinant monoclonal antibody cixutumumab.

Patients receive cixutumumab intravenously (IV) over 1 hour on days 1, 8, and 15 and doxorubicin hydrochloride IV continuously over 44-52 hours beginning on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease may continue to receive cixutumumab in the absence of disease progression or unacceptable toxicity.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed soft tissue sarcoma

    • Unresectable disease
    • Locally advanced or metastatic disease
  • The following tumor types are not allowed:

    • Embryonal and alveolar rhabdomyosarcoma
    • Gastrointestinal stromal tumor
    • Alveolar soft part sarcoma
    • Clear cell sarcoma
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
  • No more than 1 prior therapy for sarcoma
  • No known brain metastases
  • ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
  • ANC ≥ 1,500/µL
  • Platelet count ≥ 100,000/µL
  • Leukocytes ≥ 3,000/µL
  • Total bilirubin ≤ upper limit of normal(ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
  • Fasting serum glucose < 120 mg/dL OR below ULN
  • LVEF ≥ 50% by MUGA scan
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after the last dose of anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • No history of allergic reactions attributed to compounds of similar chemical or biological composition to anti-IGF-1R recombinant monoclonal antibody IMC-A12
  • No poorly controlled diabetes mellitus

    • Patients with a history of diabetes mellitus are eligible provided their blood glucose is within normal range and they are on a stable dietary or therapeutic regimen for this condition
  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia
    • Psychiatric illness or social situation that would preclude compliance with study requirements
  • No other concurrent investigational or commercial agents or therapies
  • Recovered from all prior therapy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
  • More than 4 weeks since prior major surgery, hormonal therapy (other than replacement), or hormonal therapy

    • No prior radiotherapy to the heart, mediastinum, or chest wall
  • No prior anthracycline therapy or anti-IGF-1R therapy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00720174

Locations
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Decatur Memorial Hospital
Decatur, Illinois, United States, 62526
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
Ingalls Memorial Hospital
Harvey, Illinois, United States, 60426
Joliet Oncology-Hematology Associates Limited
Joliet, Illinois, United States, 60435
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
Central Illinois Hematology Oncology Center
Springfield, Illinois, United States, 60702
United States, Indiana
Fort Wayne Medical Oncology and Hematology Inc-Parkview
Fort Wayne, Indiana, United States, 46845
United States, Maryland
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland, United States, 21201
United States, Michigan
University of Michigan University Hospital
Ann Arbor, Michigan, United States, 48109
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Saint John's Mercy Medical Center
Saint Louis, Missouri, United States, 63141
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Investigators
Principal Investigator: Rashmi Chugh University of Chicago
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00720174     History of Changes
Other Study ID Numbers: NCI-2009-00285, NCI-2009-00285, UCCRC-16227A, CDR0000600157, 16227A, 8131, P30CA014599, N01CM00071
Study First Received: July 19, 2008
Last Updated: September 9, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sarcoma
Rhabdomyosarcoma
Osteosarcoma
Leiomyosarcoma
Rhabdomyosarcoma, Embryonal
Liposarcoma
Chondrosarcoma
Sarcoma, Synovial
Hemangiosarcoma
Histiocytoma
Hemangiopericytoma
Neoplasms
Histiocytoma, Benign Fibrous
Fibrosarcoma
Histiocytoma, Malignant Fibrous
Desmoplastic Small Round Cell Tumor
Neurofibrosarcoma
Neurilemmoma
Liver Neoplasms
Mesenchymoma
Dermatofibrosarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Myosarcoma
Neoplasms, Muscle Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Adipose Tissue
Neoplasms, Vascular Tissue
Neoplasms, Fibrous Tissue

ClinicalTrials.gov processed this record on September 16, 2014