Cixutumumab and Temsirolimus in Treating Patients With Locally Recurrent or Metastatic Breast Cancer

This phase I/II trial is studying the side effects and best dose of cixutumumab when given together with temsirolimus and to see how well they work in treating patients with breast cancer that has recurred (come back) at or near the same place as the original (primary) tumor or has spread to other places in the body. Monoclonal antibodies, such as cixutumumab, can block tumor growth in different ways by targeting certain cells. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cixutumumab together with temsirolimus may be a better treatment for breast cancer.

PRIMARY OBJECTIVES:

I. To establish the recommended dose level for the phase II trial. (Phase I) II. To examine the safety profile of this combination in patients with metastatic breast cancer. (Phase I) III. To assess the anti-tumor activity (in terms of overall response rate) and toxicity profile of IMC-A12 (cixutumumab) in combination with temsirolimus in patients with metastatic breast cancer. (Phase II)

SECONDARY OBJECTIVES:

I. To estimate the progression-free survival (PFS) and overall survival distributions (as well as the 6-month PFS rate).

II. To evaluate the in vivo mechanisms of action of temsirolimus in combination with IMC-A12 and to examine potential biomarker predictors of treatment response.

OUTLINE: This is a phase I, dose-escalation study of cixutumumab followed by a phase II study.

Patients receive temsirolimus intravenously (IV) over 30 minutes and cixutumumab IV over 60 minutes on days 1, 8, 15, and 22 (cixutumumab is given on days 8, 15, and 22 of course 1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically for up to 2 (phase I) or 5 (phase II) years.

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed diagnosis of breast cancer with diagnosis of metastatic or locally recurrent disease (locally recurrent disease should be stage IV e.g. chest wall involvement)
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 (Karnofsky \>= 80%)
* Life expectancy of \> 12 weeks
* Capable of understanding investigational nature, potential risks and benefits of the study and able to provide written informed consent
* Negative serum pregnancy test =\< 7 days of registration for women of childbearing potential:

  * Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study therapy and for 3 months after the last dose of IMC-A12 and CCI-779 (temsirolimus)
  * Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  * Nursing women must be willing to discontinue nursing; NOTE: breastfeeding should be discontinued if the mother is treated with CCI-779 and IMC-A12
* Absolute neutrophil count \>= 1,500/mcL
* Hemoglobin \>= 8.5 g/dL
* Platelets \>= 100,000/mcL
* Total bilirubin =\< 1.5 X institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) =\< 3 x institutional ULN (=\< 5 X institutional ULN if liver function test \[LFT\] elevations due to liver metastases)
* Creatinine =\< 1.5 X institutional ULN OR creatinine clearance \>= 60 mL/min/1.73\^2 for patients with creatinine \> institutional ULN
* Fasting serum cholesterol =\< 350 mg/dL (9.0 mmol/L)
* Fasting triglycerides =\< 400 mg/dL (4.56 mmol/L)
* Albumin \>= 3.4 mg/dL
* Fasting or non fasting serum glucose \< 120 mg/dL
* Hemoglobin A1c (HbA1c) (for all patients with a history of diabetes mellitus) \< 8%
* Phase I only: Any number of prior therapy regimens is allowed
* Phase II only: Measurable disease is required for the Phase II portion of the study; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques (computed tomography \[CT\], magnetic resonance imaging \[MRI\], x-ray) or as \>= 10 mm with spiral CT scan
* Phase II only: =\< two and at least one prior chemotherapy regimens in the setting of metastatic or locally recurrent (stage IV chest wall involvement) disease are required

Exclusion Criteria:

* Phase I patients only: Patients with base line diabetes requiring oral hypoglycemics or insulin
* Phase II patients only: Poorly controlled diabetes mellitus; NOTE: patients with a history of diabetes mellitus on oral hypoglycemics or insulin are allowed to participate, provided that their fasting blood glucose is \< 120 mg/dL and that they are on a stable dietary or therapeutic regimen for this condition
* Any of the following:

  * Pregnant women
  * Nursing women
  * Men or women of childbearing potential who are unwilling to employ adequate contraception (hormonal agents are not allowed and oral contraceptives are not acceptable for contraception)
* Receiving hormonal agents used for the treatment of breast cancer with the exception that premenopausal women who have been on a gonadotropin-releasing hormone (GnRH) agonist and subsequently progressed may, at the discretion of the treating physician, continue on the GnRH agonist
* Any of the following prior therapies:

  * Systemic anti-cancer therapy =\< 3 weeks prior to registration
  * Radiation therapy =\< 2 weeks prior to registration
* Prior invasive non-breast malignancy, except for adequately treated basal or squamous cell carcinoma of the skin or other cancer from which the patient has been disease free for \>= 5 years
* Known hypersensitivity reactions to macrolide antibiotics (such as erythromycin, clarithromycin, and azithromycin); allergic reactions attributed to compounds of similar chemical or biologic composition to IMC-A12, or temsirolimus
* Prior treatment with agents targeting the insulin-like growth factor-I receptor (IGF-IR)/insulin-like growth factors (IGFs) or phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PI3K)/v-akt murine thymoma viral oncogene homolog 1 (Akt)/mechanistic target of rapamycin (mTOR) pathway
* Receiving any other investigational agents or herbal preparations
* Patients may not be taking oral corticosteroids except for replacement for adrenal insufficiency
* Uncontrolled brain metastases; Note: brain metastases are not permitted on study unless the metastases have been treated by surgery or radiotherapy, and the patient has been neurologically stable and off of steroids for \>= 12 weeks
* Known human immunodeficiency virus (HIV)-positive patients who have cluster of differentiation (CD)4 counts below the normal range or who are on anti-retroviral therapy that may interfere with the metabolism of temsirolimus
* Uncontrolled intercurrent illness including, but not limited to:

  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Uncontrolled symptomatic cardiac arrhythmia
  * Psychiatric illness/social situations that would limit compliance with study requirements
* Receiving enzyme-inducing antiepileptic drugs (EIAEDs; e.g., phenytoin, carbamazepine, phenobarbital) or any other cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducer such as rifampin or St. John's wort