Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma

NCT ID: NCT01016015

Last Updated: 2015-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 178 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-11-30
• Study Completion Date: 2014-07-31

Brief Summary

This phase II trial studies how well temsirolimus and cixutumumab works in treating patients with locally advanced, metastatic, or recurrent soft tissue sarcoma or bone sarcoma. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cixutumumab, can block tumor growth by blocking the ability of tumor cells to grow and spread. Giving temsirolimus with cixutumumab may be an effective treatment for soft tissue or bone sarcoma.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the proportion of patients progression-free at 12 weeks (progression free survival [PFS], defined as Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 complete response [CR] + partial response [PR] + stable disease [SD]) with (A) Insulin-like growth factor (IGF)-1receptor (R)+ soft tissue sarcomas; (B) IGF-1R+ bone tumors; or (C) IGF-1R(-) sarcomas, who are treated weekly with intravenous A12 (cixutumumab) and temsirolimus.

SECONDARY OBJECTIVES:

I. To determine the overall response rate (defined as CR + PR). II. To determine the overall survival. III. To determine the correlation of clinical outcome with pre- and post-treatment IGF-1R pathway related markers in plasma (pre and post therapy), archived tissue, and pre- and post-treatment tumor biopsies.

OUTLINE:

Patients receive cixutumumab intravenously (IV) over 60 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for at least 4 weeks.

Conditions

Metastatic Osteosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (cixutumumab and temsirolimus)

Patients receive cixutumumab IV over 60 minutes and temsirolimus IV over 30 minutes on days 1, 8, 15, 22, 29, and 36. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Cixutumumab

Intervention Type: BIOLOGICAL

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Temsirolimus

Intervention Type: DRUG

Given IV

Interventions

Cixutumumab

Given IV

Intervention Type: BIOLOGICAL

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Temsirolimus

Given IV

Intervention Type: DRUG

Other Intervention Names

Anti-IGF-1R Recombinant Monoclonal Antibody IMC-A12; IMC-A12; CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779; Torisel

Eligibility Criteria

Inclusion Criteria

• Patients must have histologically or cytologically confirmed sarcoma of soft tissue or bone; all patients will have IGF-1R testing at Memorial Sloan-Kettering Cancer Center (MSKCC) by immunohistochemistry (IHC); patients with confirmation of IGF-1R status in pre-existing tumor specimens will be enrolled on one of three arms of the study:

• Arm A: IHC IGF-1R (+) sarcomas of soft tissue
• Arm B: IHC IGF-1R (+) sarcomas of bone
• Arm C: Any IGF-1R (-) sarcomas
• Subjects must have metastatic and/or locally advanced or locally recurrent disease
• Patients treated at Memorial Sloan Kettering Cancer Center must consent to tumor biopsies before therapy and after the 2nd week of therapy; subjects who do not have accessible tumor for biopsy may be enrolled at the discretion of the Principal Investigator
• Patients must have measurable disease by RECIST 1.1; measurable disease (a 'target' lesion) is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT) (CT scan slice thickness no greater than 5 mm); >= 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable); and >= 20 mm by chest x-ray
• A minimum of 1 and a maximum of 4 prior systemic therapy regimens for recurrent/metastatic disease; the last dose of systemic therapy (include tyrosine kinase inhibitors) must have been given at least 4 weeks prior to initiation of therapy; patients receiving carmustine (BCNU) or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy
• Patients with brain metastasis that have been treated with definitive surgery or radiation and have been clinically stable for 3 months following the procedure with no neurological signs or symptoms and no requirement for systemic glucocorticoids are eligible for study
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Absolute neutrophil count >= 1.5 x 10^9/l; patients with neutropenia on a familial basis may still be enrolled on study; please contact the Principal Investigator (PI) who will discuss the patient with Cancer Therapy Evaluation Program (CTEP)
• Platelets >= 100 x 10^9/l
• Total bilirubin =< 1.5 x upper limit of normal (ULN); in patients with bilirubin > 1-1.5 X ULN, the starting dose of temsirolimus is 15 mg/week
• Albumin >= 3 g/dL
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT)/alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) =< 3.0 x institution ULN; in patients with ALT or AST elevated > 1.0- 3.0 X ULN, the starting dose of temsirolimus is 15 mg/week
• Serum creatinine =< 1.5 x ULN
• Serum glucose =< 120 mg/dL; nonfasting or fasting; if a patient has a non-fasting glucose of over 120 mg/dL, the patient may be retested in the fasting state to determine if they are eligible for study; a non-fasting glucose of 120 or less renders the patient eligible for study
• Fasting total cholesterol =< 300 mg/dL
• Fasting triglycerides =< 300 mg/dL; patients with neutropenia on a familial basis may still be enrolled on study; please contact the PI who will discuss the patient with CTEP
• Patients must not have current evidence of another malignancy
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) and have pregnancy testing prior to study entry and for the duration of study participation (every 2 cycles of therapy); should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Adverse events related to prior tumor-specific therapy must have resolved to less than or equal to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0) grade 1 prior to study entry (except alopecia)
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Patients who have had major surgery or a course of glucocorticoid therapy lasting longer than 5 days within 4 weeks prior to entering the study, or those who have not recovered from adverse events to =< NCI CTCAE (version 4.0) grade 1, associated with surgery; excluded from such considerations are surgical changes not expected to improve, e.g. removal of muscle tissue; patients may be on replacement glucocorticoids for pre-existing glucocorticoid deficiency (e.g. Addison's disease) or topical glucocorticoids for dermatological conditions (e.g. psoriasis)
• Patients must be >= 4 weeks beyond treatment of any systemic therapy, other investigational therapy, biological, targeted agents or radiotherapy, and must have recovered to =< Grade 1 toxicity or previous baseline for each toxicity; specifically excluded are the laboratory examinations serum lipase or amylase (without overt pancreatitis), hypophosphatemia, hypomagnesemia, and lymphopenia; patients may have received palliative low dose radiotherapy to the limbs 1-4 weeks before this therapy provided pelvis, sternum, scapulae, vertebrae, or skull were not included in the radiotherapy field
• Patients may not have received prior IGFR1 inhibitors
• Patients may not have received prior mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus, everolimus, ridaforolimus, or temsirolimus)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus, A12, or other agents used in the study
• Patients with hyperglycemia, defined as fasting serum glucose above 120 mg/dl, or those patients already on oral anti-diabetic or insulin therapy
• Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including human immunodeficiency virus (HIV), active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (specifically, atrial fibrillation or ventricular dysrhythmias except ventricular premature contractions), or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women and women who are breast-feeding

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Tap

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, United States

Mayo Clinic in Florida

Jacksonville, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Decatur Memorial Hospital

Decatur, Illinois, United States

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, United States

Memorial Medical Center

Springfield, Illinois, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

University of Michigan University Hospital

Ann Arbor, Michigan, United States

University of Michigan

Ann Arbor, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

SUNY College at Old Westbury

Old Westbury, New York, United States

Albert Einstein College of Medicine

The Bronx, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Carolinas Medical Center

Charlotte, North Carolina, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

M D Anderson Cancer Center

Houston, Texas, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Cross Cancer Institute

Edmonton, Alberta, Canada

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Countries

United States; Canada

References

Schwartz GK, Tap WD, Qin LX, Livingston MB, Undevia SD, Chmielowski B, Agulnik M, Schuetze SM, Reed DR, Okuno SH, Ludwig JA, Keedy V, Rietschel P, Kraft AS, Adkins D, Van Tine BA, Brockstein B, Yim V, Bitas C, Abdullah A, Antonescu CR, Condy M, Dickson MA, Vasudeva SD, Ho AL, Doyle LA, Chen HX, Maki RG. Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial. Lancet Oncol. 2013 Apr;14(4):371-82. doi: 10.1016/S1470-2045(13)70049-4. Epub 2013 Mar 8.

Reference Type: DERIVED

PMID: 23477833 (View on PubMed)

Other Identifiers

NCI-2011-01408

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000659358

Identifier Type: -

Identifier Source: secondary_id

09-097

Identifier Type: OTHER

Identifier Source: secondary_id

8121

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00032

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00038

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00071

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM00100

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA008748

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-01408

Identifier Type: -

Identifier Source: org_study_id