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)

• Drug: PF-05212384 (gedatolisib)
  PF-05212384 weekly intravenous infusions starting at 90 mg/wk as a 3 week cycle
• Drug: Docetaxel
  Docetaxel intravenous infusions once every 3 weeks starting at 75 mg/m^2
• Drug: Cisplatin
  Cisplatin intravenous infusions once every 3 weeks starting at 75 mg/m^2
• Drug: Dacomitinib
  Dacomitinib to be taken orally as a continuous once daily regimen at a starting dose of 30 mg

• Experimental: Arm A
  Interventions:

  • Drug: PF-05212384 (gedatolisib)
  • Drug: Docetaxel
• Experimental: Arm B
  Interventions:

  • Drug: PF-05212384 (gedatolisib)
  • Drug: Cisplatin
• Experimental: Arm C
  Interventions:

  • Drug: PF-05212384 (gedatolisib)
  • Drug: Dacomitinib
• Experimental: Expansion Arm 1
  Interventions:

  • Drug: PF-05212384 (gedatolisib)
  • Drug: Cisplatin
• Experimental: Expansion Arm 2
  Interventions:

  • Drug: PF-05212384 (gedatolisib)
  • Drug: Cisplatin

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.