Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma
Condition: Metastatic Osteosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Osteosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma
MeSH terms: Sarcoma; Osteosarcoma; Recurrence
Intervention: Cixutumumab; Laboratory Biomarker Analysis; Temsirolimus
Intervention description: Given IV; Correlative studies; Given IV
Intervention MeSH terms: Sirolimus; Temsirolimus; MTOR Inhibitors; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 178.0
Sex: All
Minimum age: 16 Years
Healthy volunteers: No

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.
    

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