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)

Pfizer

Status and phase: Completed; Phase 1

Conditions: Neoplasm

Treatments: Drug: Cisplatin; Drug: Dacomitinib; Drug: PF-05212384 (gedatolisib); Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT01920061

2013-001390-24 (EudraCT Number)

B2151002

Details and patient eligibility

About

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).

Enrollment: 110 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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110 participants in 5 patient groups

Arm A

Experimental group

Treatment:

Drug: Docetaxel

Drug: PF-05212384 (gedatolisib)

Arm B

Experimental group

Treatment:

Drug: PF-05212384 (gedatolisib)

Drug: Cisplatin

Arm C

Experimental group

Treatment:

Drug: PF-05212384 (gedatolisib)

Drug: Dacomitinib

Expansion Arm 1

Experimental group

Treatment:

Drug: PF-05212384 (gedatolisib)

Drug: Cisplatin

Expansion Arm 2

Experimental group

Treatment:

Drug: PF-05212384 (gedatolisib)

Drug: Cisplatin