Clinical trial NCT00720174: Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma
Official title: A Phase 1 Study of Doxorubicin and A12 in Advanced Soft Tissue Sarcoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-07-22
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: 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
timeFrame: Up to 2 courses of treatment
Secondary outcomes:
measure: Changes in cardiac function as measured by MUGA scans of the left ventricular ejection fraction
timeFrame: Baseline to 6 courses of treatment
measure: Confirmed response rate (CR + PR) for comparison with doxorubicin treatment in similar historical patient populations
timeFrame: Up to 6 months
measure: Overall survival
timeFrame: Until death due to any cause, or loss to follow-up, assessed up to 6 months
measure: Progression-free survival
timeFrame: Until documented disease progression or death or loss-to-follow-up, assessed up to 6 months
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago Comprehensive Cancer Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem-Evanston Hospital
state: Illinois
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates Limited
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare-Peoria
state: Illinois
city: Springfield
country: United States
facility: Central Illinois Hematology Oncology Center
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology Inc-Parkview
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland/Greenebaum Cancer Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Saint Louis
country: United States
facility: Mercy Hospital Saint Louis
state: Missouri
city: Milwaukee
country: United States
facility: Froedtert and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Chicago Comprehensive Cancer Center
name: Rashmi Chugh
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chugh R, Griffith KA, Davis EJ, Thomas DG, Zavala JD, Metko G, Brockstein B, Undevia SD, Stadler WM, Schuetze SM. Doxorubicin plus the IGF-1R antibody cixutumumab in soft tissue sarcoma: a phase I study using the TITE-CRM model. Ann Oncol. 2015 Jul;26(7):1459-64. doi: 10.1093/annonc/mdv171. Epub 2015 Apr 9.