Cisplatin and Paclitaxel With or Without Everolimus in Treating Patients With Stage II or Stage III Breast Cancer
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: cisplatin; everolimus; paclitaxel; placebo; Venous blood draw
Intervention description: Given IV; Given orally; Given IV; Given orally; Venous blood (2-3 tablespoons) will be taken for germline DNA analysis to complement the correlative studies in the tumor tissue. Blood can be drawn at any time prior, during, or after completion of study treatment
Intervention MeSH terms: Paclitaxel; Everolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 145.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: triple-negative breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; male breast cancer

Summary:

      RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Giving chemotherapy together
      with everolimus before surgery may make the tumor smaller and reduce the amount of normal
      tissue that needs to be removed. It is not yet known whether cisplatin and paclitaxel are
      more effective when given together with or without everolimus in treating patients with
      breast cancer.

      PURPOSE: This randomized phase II trial is studying how well cisplatin and paclitaxel work
      when given together with or without everolimus in treating patients with stage II or stage
      III breast cancer.
    

Eligibility criteria:

        Eligibility criteria

        -Maximum number of patients will include two-thirds of the patients in Arm 1 and one-third
        of the patients for Arm 2 (total of 145 patients). Estimated time for accrual with ~ 3
        patients/month would be ~ 3.5 years.

        Inclusion criteria:

          -  Patients must provide informed written consent.

          -  Patient must be ≥ 18 years of age.

          -  ECOG performance status 0-1.

          -  Clinical stage II or stage III triple-negative (ER and/or PR no staining or weak
             staining in less than or equal to 10% cells by immunohistochemistry [IHC] and
             HER2-negative by Herceptest [0, 1+] or FISH) invasive mammary carcinoma, confirmed by
             histological analysis.

          -  Patients who have measurable* residual tumor at the primary site

             *Measurable disease: any mass that can be reproducibly measured by physical
             examination, mammogram, and/or ultrasound and can be accurately measured in at least
             one dimension (longest diameter to be recorded) as 10 mm (1 cm), either in the breast
             or axillary lymph nodes.

          -  Available core biopsies from the time of diagnosis. Fresh tissue must be obtainable at
             baseline or fresh tissue biopsy prior to treatment initiation.

          -  Patients who will undergo surgical treatment with either segmental resection or total
             mastectomy.

          -  Patients must have adequate hematologic, hepatic, and renal function. All tests must
             be obtained less than 4 weeks from study entry. This includes:

          -  ANC >/=1500/mm3

          -  Platelet count >/=100,000/mm3

          -  Creatinine </=1.5X upper limits of normal

          -  Bilirubin, SGOT, SGPT </=1.5X upper limits of normal*

             * for patients with Gilbert"s syndrome, direct bilirubin will be measured instead of
             total bilirubin.

          -  The patient must have not had anyprior chemotherapy for primary breast cancer.

          -  Patients with a prior history of contra-lateral breast cancer are eligible if they
             have no evidence of recurrence of their initial primary breast cancer within the last
             5 years.

          -  Able to swallow and retain oral medication.

          -  Four days prior to biopsy procedures patients must be off medications that could
             increase risk of bleeding (i.e. ASA, NSAIDS, Coumadin, heparin products)

          -  Potential subjects must complete all screening assessments as outlined in the
             protocol.

          -  The pre-menopausal patient of childbearing potential must have had a negative
             pregnancy test and agreed to use birth control methods while participating in the
             study. Note: Women of childbearing potential and their male counterparts should use a
             barrier method of contraception during and for 3 months following protocol therapy.

        Ineligibility Criteria

        Exclusion Criteria:

          -  Locally recurrent breast cancer.

          -  Pregnant or lactating women.

          -  Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)

          -  Use of CYP3A4 modifiers (Appendix A)

          -  Serious medical illness that in the judgment of the treating physician places the
             patient at high risk of operative mortality.

          -  Malabsorption syndrome, disease significantly affecting gastrointestinal function, or
             resection of the stomach or small bowel.

          -  History of other malignancy. Subjects who have been disease-free for 5 years, or
             subjects with a history of completely resected non-melanoma skin cancer or
             successfully treated in situ carcinomas are eligible.

          -  History of hepatitis B or hepatitis C. If patient is judged to be at risk for having
             had exposure to viral B or C hepatitis (i.e. illicit IV drug use, blood transfusion
             prior to 1990, body piercing, tattoos, etc.), appropriate testing should be performed
             (i.e. Hepatitis B surface antigen antibody, and Hepatitis C antibody)

          -  Active or uncontrolled infection requiring parenteral antibiotics.

          -  Dementia, altered mental status, or any psychiatric condition that would prohibit the
             understanding or rendering of informed consent.

          -  Symptomatic neuropathy (≥ grade 2).

          -  Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery,
             immunotherapy, hormonal therapy, or any other biologic therapy) other than the ones
             specified in the protocol.

          -  Concurrent treatment with an investigational agent.

          -  Used an investigational drug within 15 days or 5 half-lives, whichever is longer,
             preceding the first dose of randomized therapy.