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Protocol No. UW18107

Principal Investigator Wisinski, Kari

Phase I/II

Age Group Adult

Scope National

Sponsor Type Industry; Institutional

Title Phase 2 Trial with Safety Run-In of Gedatolisib Plus Talazoparib in Advanced Triple Negative or BRCA1/2 Positive, HER2 Negative Breast Cancers

Objective Since your tumor does not have the three common breast cancer receptors (estrogen, progesterone, HER-2), researchers are looking for other receptors to block
Talazoparib is a targeted therapy. Talazoparib blocks an enzyme called PARP. PARP enzymes are involved in DNA transcription (copying), cell cycle regulation, and DNA repair. Talazoparib causes cancer cells to die by breaking the tumor DNA and then stopping the tumor from repairing the damaged DNA
Gedatolisib is also a targeted therapy. It blocks two receptors called PI3 kinase (PI3K) and mTOR. The PI3K and mTOR pathways help cells to grow, survive and become resistant to chemotherapy and radiotherapy. By blocking these pathways, gedatolisib may cause cancer cells to die and stop growing
Researchers think that combining talazoparib and gedatolisib will have more benefits than giving either drug on its own. This study is being done to find the safe dose of talazoparib combined with gedatolisib and to find out if the combination has any effect on triple negative breast cancer
The study drugs could shrink your cancer but could also cause side effects. This study will help the researchers to know whether this different approach is better, the same, or worse than the usual approach

Treatment The study drugs will be given in units of time called cycles. One cycle equals 28 days (4 weeks). If you are eligible and agree to participate, you will receive the study drugs as described below:
  • Talazoparib is a pill that you will take once every day
  • Gedatolisib will be given once every week. Gedatolisib will be given through a vein (IV), which is also called an infusion. Each infusion will take about 30 minutes.

  • Description Phase 2 with Safety Run-In of Gedatolisib plus Talazoparib in Advanced Triple Negative Breast Cancer or BRCA 1/2+, HER2-BC

    Key Eligibility
  • Male or female 18 years of age or older at time of consent
  • Subjects with histologically or confirmed breast cancer that is advanced (defined as metastatic or unresectable)
  • Phase II Cohort A: Patients with advanced triple negative breast cancer (TNBC) with negative or unknown germline BRCA status. Variants of undetermined significance in BRCA 1/2 should be considered negative
  • Phase II Cohort B: Patients with advanced HER2 negative breast cancer and a germline BRCA1 or 2 (1/2) mutation
  • Phase I run-in: meets criteria for either cohort A or B
  • Measurable disease by RECIST 1.1 is required
    Prior therapy:
  • Cohort A: At least one line of prior systemic therapy for advanced breast cancer (chemotherapy or other targeted therapy allowed). No more than 2 lines of prior chemotherapy for advanced disease are allowed
  • Cohort B: No more than 2 lines of prior chemotherapy for advanced disease are allowed. No limit on prior endocrine or targeted therapies
  • Both cohorts: no prior PARP inhibitor for advanced breast cancer
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  • Adequate organ function as defined by the protocol
  • Archived tumor tissue available (Metastatic disease from non-bone and non-brain sites preferred, but primary breast or lymph node tissue is permitted
  • Ability to take oral medications
  • No history of type I diabetes. For patients with known type II diabetes, must have controlled diabetes (Hgb A1c less than 7.0 mmol/L within 30 days of study entry) with no more than one oral antidiabetic agent and no insulin
  • No active central nervous system (CNS) metastatic disease
  • Can not be pregnant or breast feeding
  • Male and Female of child bearing potential must agree to adequate birth control as defined by the protocol
    EXCLUSION
  • Active infection requiring systemic therapy. Patients with a known history of HIV must have a CD4 count greater than or equal to the institutional lower limit of normal within 28 days prior to registration
  • Patients with HIV must also be on a stable anti-retroviral regimen for greater than or equal to 28 days before registration
  • Patients who have had chemotherapy, targeted therapy, or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from acute effects of any prior therapy to baseline or Grade less than or equal to 1. Grade 2 or higher exceptions include alopecia, up to grade 2 neuropathy or other Grade 2 AEs or lab values not constituting a safety risk in the opinion of the treating physician
  • Known hypersensitivity to any of the excipients of gedatolisib or talazoparib
  • Any impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study medications
  • Known active hepatitis B or C, Patients who have completed curative therapy for HCV are eligible
  • Known history of myelodysplastic syndrome or acute myeloid leukemia
  • Subjects with any of the following conditions: History of drug-induced pneumonitis, history of abdominal fistula, gastrointestinal perforation, or intra- abdominal abscess, Any history of cerebrovascular accident (CVA) or transient ischemic attack, Symptomatic congestive heart failure, Clinically significant cardiac ventricular arrhythmias, or Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome
  • Currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise

  • Applicable Disease Sites Breast

    Status Open

    Participating Institutions UW Hospital and Clinics; UWCCC 1 South Park