A Study Of PF-05212384 In Combination With Other Anti-Tumor Agents and in Combination With Cisplatin in Patients With Triple Negative Breast Cancer in an Expansion Arm (TNBC)
Condition: Neoplasm
MeSH terms: Triple Negative Breast Neoplasms
Intervention: PF-05212384 (gedatolisib); Docetaxel; Cisplatin; Dacomitinib
Intervention description: PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle; Docetaxel intravenous infusions once every 3 weeks starting at 75 mg/m^2; Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2; Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg
Intervention MeSH terms: Docetaxel; Gedatolisib
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 110.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced cancer; solid tumors; PI3K; mTOR; PI3K/mTOR; metastatic; Triple Negative Breast Cancer (TNBC)

Summary:

      This study will evaluate PF-05212384 (gedatolisib) PI3K/mTOR inhibitor)) in combination with
      either docetaxel, cisplatin or dacomitinib in select advanced solid tumors. The study will
      assess the safety, pharmacokinetics and pharmacodynamics of these combinations in patients
      with advanced cancer in order to determine the maximum tolerated dose in each combination.
      The cisplatin combination expansion portion will evaluate the anti tumor activity of PF
      05212384 plus cisplatin in patients with TNBC in 2 separate Arms (Arm 1 and Arm 2).
    

Eligibility criteria:

        Inclusion Criteria:

        Cisplatin Combination Expansion:

        Arm 1:Patients with TNBC with no prior cytotoxic chemotherapy therapy in the metastatic
        setting; Arm 2: Patients with TNBC and one or two prior cytotoxic therapies in the
        metastatic setting.

          -  Arm A: castrate resistant prostate cancer, advanced breast cancer, or non-small cell
             lunch cancer that are candidates for treatment with a docetaxel-based combination.

          -  Arm B: Urothelial transitional cell cancer, triple negative breast cancer, ovarian
             cancer or non small cell lunch cancer that are candidates for a cisplatin-based
             combination.

          -  Arm C: Her2+ breast cancer refractory to prior herceptin or lapatinib, her2+
             esophagal-gastric cancer, head and neck squamous cell cancer, or non small cell lunch
             cancer that are candidates for treatment with a dacomitinib-based combination.

          -  Availability of archival tumor biopsy sample or willing to provide fresh biopsy if not
             available.

          -  Eastern Cooperative Oncology Group [ECOG] performance must be 0 or 1.

          -  Adequate bone marrow, renal and liver function.

        Exclusion Criteria:

          -  Prior therapy for Cisplatin Combination Expansion:

               -  Prior platinum (carboplatin or cisplatin) in either the adjuvant or metastatic
                  setting;

               -  Prior radiation to >25% bone marrow as estimated by the Investigator.

          -  Patients with known symptomatic brain metastases.

          -  Chemotherapy, radiotherapy, biologics or investigational agent within 4 weeks of the
             lead-in dose.

          -  Major surgery within 4 weeks of the baseline disease assessments.

          -  >2 prior regimens containing cytotoxic chemotherapy in the metastatic setting.

          -  Active bacterial, fungal or viral infection.

          -  Uncontrolled or significant cardiovascular disease.