MDACC Study Summary 2010-0191 (Archived)

Study Summary
No. 2010-0191:.......Sarcoma......Joseph A. Ludwig......Sarcoma Medical Oncology

Study Summary Title



Study Summary Number:	2010-0191

Study Title:	A phase 2 study of temsirolimus (CCI-779, NSC 683864) and IGF-1 receptor antibody cixutumumab (IMC-A12 (NSC 742460) in patients with metastatic sarcomas

Physician

New Patient Referral



Name:	Joseph A. Ludwig	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Sarcoma Medical Oncology	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-792-3626 Contact us about clinical trials

General Information



Disease Group:	Sarcoma	Supported By:	National Cancer Institute's Cancer Therapy Evaluation Program (CTEP)

Phase of Study:	Phase II	Return Visit:

Treatment Agents:	CCI-779 IMC-A12	Home Care:

Treatment Loc:	Both at MDACC & and Other Sites

Estimated Length of Stay in Houston:


Description/ Intervention:	The goal of this clinical research study is to learn about the status of sarcoma after receiving temsirolimus and IMC-A12. The safety of this combination will also be studied.

Study Objectives / Outcomes

Primary Objectives
The primary endpoint of this study is to determine the proportion of patients progression-free at 12 weeks (PFS, defined as RECIST 1.1 CR + PR + SD) with (A) IGF-1R+ soft tissue sarcomas; (B) IGF-1R+ bone tumors; or (C) IGF-1R(-) sarcomas, who are treated weekly with intravenous A12 and temsirolimus.

Secondary Objectives
Secondary endpoints include determination of:
(1) Overall response rate (defined as CR + PR)
(2) Overall survival
(3) 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. Serum markers will be examined at Memorial Hospital (60 patients anticipated). Such sample collection will be optional at outside sites (20 patients anticipated). Pre and post treatment biopsies will be performed in all patients treated only at Memorial Hospital with safely accessible tumors (35 patients anticipated). Once target accrual has been met for the correlatives or per the Memorial Sloan-Kettering Cancer Center (MSKCC) PI's discretion, no additional samples or biopsies will be collected. Participating sites will be instructed by MSKCC to no longer collect plasma samples.

Study Status Information



Study Activation / Registration Date:	09/08/2010

IRB Review and Approval Date:	09/08/2010

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Terminated

Projected Accrual:	174

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Screening portion of the study:Patients must have histologically or cytologically confirmed sarcoma of soft tissue or bone. Confirmation will be done at MSKCC or locally for participating sites.

2) Screening portion of the study:Patient must have evidence of recurrent or metastatic disease by physical examination or by imaging studies

3) Screening portion of the study:Age >/= to 16 years. In addition, for all participating sites, patients >/= to 16 years old must also be assessed for eligibility by the site investigator.

4) Screening portion of the study:ECOG performance status 0 or 1

5) Screening portion of the study:Patients must not have current evidence of another malignancy

6) Screening portion of the study:Ability to understand and the willingness to sign a written informed consent document

7) Treatment portion of the study:Patients must have histologically or cytologically confirmed sarcoma of soft tissue or bone. All patients will have IGF-1R testing at 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

8) Treatment portion of the study:Subjects must have metastatic and/or locally advanced or locally recurrent disease

9) Treatment portion of the study: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.)

10) Treatment portion of the study: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 greater than/= to 10 mm when measured by CT (CT scan slice thickness no greater than 5 mm); greater than/= to 10 mm caliper measurement by clinical exam (lesions which cannot be accurately measured with calipers should be recorded as non-measurable); and greater than/= to 20 mm by chest x-ray.

11) Treatment portion of the study: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 BCNU or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy.

12) Treatment portion of the study: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.

13) Treatment portion of the study:Age >/= to 16 years. In addition, for all participating sites, patients >/= 16 years old must also be assessed for eligibility by the site investigator.

14) Treatment portion of the study:ECOG performance status 0 or 1.

15) Treatment portion of the study:Patients must have normal organ and marrow function as defined below (ULN indicates institutional upper limit of normal):Absolute neutrophil count >/= to 1.5x10^9/l, Platelets > than/= to 100 x 10^9/l, Total bilirubin < than/= to 1.5 ULN, Albumin > than/= to 3 g/dL, AST(SGOT)/ALT(SGPT) </= to 3.0 institutional ULN ~,Serum creatinine < than/= to 1.5 ULN, Serum glucose < than/= to 120 mg/dL* *,Fasting total cholesterol < than/= to 300 mg/dL ,Fasting triglycerides < than/= to 300 mg/dL*. *Pts with neutropenia on a familial basis may still be enrolled on study; contact the PI who will discuss the pt with CTEP.* *Nonfasting or fasting. If a pt has a non-fasting glucose of over 120 mg/dL, the pt may be retested in the fasting state to determine if they are eligible for study. A non-fasting glucose of 120 or < renders the pt eligible for study.~In pts with bilirubin >1.5 x ULN, or ALT or AST elevated >1.0-3.0 x ULN, the starting dose of temsirolimus is 15 mg/wk.

16) Treatment portion of the study:Patients must not have current evidence of another malignancy.

17) Treatment portion of the study:The effects of A12 and temsirolimus on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because mTOR inhibitors and IGF-1R inhibitors are possibly teratogenic, 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.

18) Treatment portion of the study:Adverse events related to prior tumor-specific therapy must have resolved to less than or equal to NCI CTCAE (Version 4.0) grade 1 prior to study entry (except alopecia)

19) Treatment portion of the study:Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

1) Treatment portion of the study: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 less than/= 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).

2) Treatment portion of the study:Patients must be >/= to 4 weeks beyond treatment of any systemic therapy, other investigational therapy, biological, targeted agents or radiotherapy, and must have recovered to </= 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.

3) Treatment portion of the study:Patients may not have received prior IGFR1 inhibitors.

4) Treatment portion of the study:Patients may not have received prior mTOR inhibitors (such as sirolimus, everolimus, ridaforolimus, or temsirolimus).

5) Treatment portion of the study:History of allergic reactions attributed to compounds of similar chemical or biologic composition to temsirolimus, A12, or other agents used in the study.

6) Treatment portion of 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.

7) Treatment portion of the study:Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including 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.

8) Treatment portion of the study:Pregnant women and women who are breast-feeding.

Links

Registration Number: NCT01016015
Study Information on Clinical Trials Registry (clinicaltrials.gov)