Eribulin in Combination With Cyclophosphamide in Patients With Solid Tumor Malignancies
Condition: Malignant Solid Tumour; Breast Cancer Nos Metastatic Recurrent; Neuropathy
MeSH terms: Breast Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The purpose of this study is to test the safety of eribulin (Halaven™) and cyclophosphamide
      (Cytoxan®) given together at different doses. This study will look at what effects, good
      and/or bad, that these drugs have on solid tumors. Eribulin is a drug that has been approved
      by the FDA for breast cancer that has spread to other parts of the body. Cyclophosphamide has
      been approved for different types of cancers (including breast cancer). However, the
      combination of eribulin and cyclophosphamide is considered experimental; that means this
      combination has not been approved by the FDA.

      The funding for this study is provided by Eisai Inc., the maker of eribulin.
    

Detailed description: 
      This is a phase Ib/II trial designed to determine the maximum tolerated dose (MTD) and does
      limiting toxicities (DLTs) of the combination of eribulin and cyclophosphamide in solid
      tumors and make preliminary estimates regarding efficacy of this treatment in patients with
      advanced breast cancer.

      The study includes a standard dose-confirmation schema (phase Ib portion) enrolling 3 to 6
      patients/subjects, with any solid tumors, per cohort (3+3 design) with a total of 18
      patients. The dose-expansion (phase II portion) will enroll 40 patients with advanced breast
      cancer to detect an effect size of 15% with a power of 80% with endpoints of safety,
      efficacy, and clinical benefit rate. A maximum of 58 patients will be enrolled on the phase
      Ib and II portions of this trial combined and will be treated until disease progression or
      toxicity mandate treatment change.

      Eribulin is a non-taxane microtubule inhibitor that is FDA approved as monotherapy for the
      treatment of taxane and anthracycline resistant metastatic breast cancer. The combination of
      docetaxel and cyclophosphamide is a well-accepted adjuvant chemotherapy regimen that has
      become an increasingly common therapeutic choice for intermediate risk early stage breast
      cancer. Eribulin has a favorable toxicity profile compared to docetaxel with the most common
      adverse reactions (incidence ≤25%) including neutropenia, anemia, asthenia/fatigue, alopecia,
      peripheral neuropathy, nausea, and constipation. Eribulin appears to have activity in taxane
      resistant disease, making it an attractive partner with cyclophosphamide.

      Neuropathy can be a devastating complication from adjuvant chemotherapy and in the metastatic
      setting, may limit effective therapy and reduce quality of life. Understanding the host
      factors that predict risk for neuropathy is critical, as these patients may in particular
      benefit from the lower risk of neuropathy associated with eribulin therapy. In conjunction
      with this trial, we have included correlative studies to study the proposed pharmacogenomic
      factors associated with risk of neuropathy. In this way we will potentially be able to
      identify patients who could preferentially be treated with less neurotoxic microtubule
      inhibitors.
    

Intervention name(s): Eribulin; Cyclophosphamide
Intervention type(s): Drug; Drug
Intervention description(s): Given intravenously (IV)
Phase II: Eribulin mesylate (mg/m2) + Cyclophosphamide (mg/ m2) for advanced breast cancer participants only; Given IV
Other intervention name(s): Halaven; E7389; ER-086526; Cytoxan
Intervention MeSH terms: Cyclophosphamide
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Solid tumor; Metastatic breast cancer; Unresectable or metastatic carcinoma; Neuropathy; Eribulin; Cyclophosphamide