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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00720174

Collaborator

(none)

Enrollment

Locations

Arm

2.3

Patients Per Site

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Adult Angiosarcoma Adult Desmoplastic Small Round Cell Tumor Adult Epithelioid Sarcoma Adult Extraskeletal Myxoid Chondrosarcoma Adult Extraskeletal Osteosarcoma Adult Fibrosarcoma Adult Leiomyosarcoma Adult Liposarcoma Adult Malignant Mesenchymoma Adult Malignant Peripheral Nerve Sheath Tumor Adult Rhabdomyosarcoma Adult Synovial Sarcoma Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone Childhood Angiosarcoma Childhood Desmoplastic Small Round Cell Tumor Childhood Epithelioid Sarcoma Childhood Fibrosarcoma Childhood Leiomyosarcoma Childhood Liposarcoma Childhood Malignant Mesenchymoma Childhood Malignant Peripheral Nerve Sheath Tumor Childhood Pleomorphic Rhabdomyosarcoma Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features Childhood Synovial Sarcoma Dermatofibrosarcoma Protuberans Malignant Adult Hemangiopericytoma Malignant Childhood Hemangiopericytoma Metastatic Childhood Soft Tissue Sarcoma Previously Treated 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 Untreated Childhood Rhabdomyosarcoma	Biological: Cixutumumab Drug: Doxorubicin Hydrochloride Other: Laboratory Biomarker Analysis	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

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:

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

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma

Study Start Date :

Jun 1, 2008

Actual Primary Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
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: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI) ADM Adriacin Adriamycin Adriamycin Hydrochloride Adriamycin PFS Adriamycin RDF ADRIAMYCIN, HYDROCHLORIDE Adriamycine Adriblastina Adriblastine Adrimedac Chloridrato de Doxorrubicina DOX DOXO-CELL Doxolem Doxorubicin.HCl Doxorubin Farmiblastina FI 106 FI-106 hydroxydaunorubicin Rubex Other: Laboratory Biomarker Analysis Correlative studies

Arm

Intervention/Treatment

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:

5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)

ADM

Adriacin

Adriamycin

Adriamycin Hydrochloride

Adriamycin PFS

Adriamycin RDF

ADRIAMYCIN, HYDROCHLORIDE

Adriamycine

Adriblastina

Adriblastine

Adrimedac

Chloridrato de Doxorrubicina

DOX

DOXO-CELL

Doxolem

Doxorubicin.HCl

Doxorubin

Farmiblastina

FI 106

FI-106

hydroxydaunorubicin

Rubex

Other: Laboratory Biomarker Analysis

Correlative studies

Outcome Measures

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 [Up to 2 courses of treatment]
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

Changes in cardiac function as measured by MUGA scans of the left ventricular ejection fraction [Baseline to 6 courses of treatment]
Confirmed response rate (CR + PR) for comparison with doxorubicin treatment in similar historical patient populations [Up to 6 months]
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.
Overall survival [Until death due to any cause, or loss to follow-up, assessed up to 6 months]
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.
Progression-free survival [Until documented disease progression or death or loss-to-follow-up, assessed up to 6 months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
2	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
3	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
4	Ingalls Memorial Hospital	Harvey	Illinois	United States	60426
5	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
6	Loyola University Medical Center	Maywood	Illinois	United States	60153
7	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
8	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
9	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
10	University of Maryland/Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
11	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
12	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
13	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226