Description:
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).
Title
- Brief Title: 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)
- Official Title: A PHASE 1B OPEN-LABEL THREE-ARM MULTI-CENTER STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF PF-05212384 (PI3K/MTOR INHIBITOR) IN COMBINATION WITH OTHER ANTI-TUMOR AGENTS
Clinical Trial IDs
- ORG STUDY ID:
B2151002
- SECONDARY ID:
2013-001390-24
- NCT ID:
NCT01920061
Conditions
Interventions
Drug | Synonyms | Arms |
---|
PF-05212384 (gedatolisib) | | Arm A |
Docetaxel | | Arm A |
Cisplatin | | Arm B |
Dacomitinib | | Arm C |
Purpose
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).
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A | Experimental | | - PF-05212384 (gedatolisib)
- Docetaxel
|
Arm B | Experimental | | - PF-05212384 (gedatolisib)
- Cisplatin
|
Arm C | Experimental | | - PF-05212384 (gedatolisib)
- Dacomitinib
|
Expansion Arm 1 | Experimental | | - PF-05212384 (gedatolisib)
- Cisplatin
|
Expansion Arm 2 | Experimental | | - PF-05212384 (gedatolisib)
- Cisplatin
|
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.
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of participants with Dose-limiting toxicities (DLT) |
Time Frame: | up to 21 days |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Maximum Observed Plasma Concentration (Cmax) |
Time Frame: | pre-dose, 0.5 hrs, 1, 1.5 2, 4, 6, 24, 72, 96 and 168 hours post-dose on the first two dose of study treatment |
Safety Issue: | |
Description: | Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Relatedness to [study drug] was assessed by the investigator (Yes/No). Participants with multiple occurrences of an AE within a category were counted once within the category. |
Measure: | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |
Time Frame: | pre-dose, 0.5 hrs, 1, 1.5 2, 4, 6, 24, 72, 96 and 168 hours post-dose around the first two dose of study treatment |
Safety Issue: | |
Description: | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
Measure: | Time to Reach Maximum Observed Plasma Concentration (Tmax) |
Time Frame: | pre-dose, 0.5 hrs, 1, 1.5 2, 4, 6, 24, 72, 96 and 168 hours post-dose around the first two dose of study treatment |
Safety Issue: | |
Description: | |
Measure: | Gene sequence data |
Time Frame: | Paired biopsies collected at screening and on Cycle 2 Day 8 |
Safety Issue: | |
Description: | Expression of biomarkers eg. PIK3CA, KRAS |
Measure: | QTc interval |
Time Frame: | Screening, Cycle 1 Day 2, Subsequent cycles on Day 1, 1 hour post infusion of PF-05212384, and end of treatment (Arm C only) |
Safety Issue: | |
Description: | QT interval corrected for heart rate using standard correction factors |
Measure: | Objective tumor response |
Time Frame: | Baseline up to 18 months |
Safety Issue: | |
Description: | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death according to RECIST |
Measure: | Levels of PI3K pathway protein biomarkers |
Time Frame: | Paired biopsies collected at screening and on Cycle 2 Day 8 |
Safety Issue: | |
Description: | Expression of biomarkers eg. pAkt, PTEN, circulating insulin |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Pfizer |
Trial Keywords
- Advanced cancer
- solid tumors
- PI3K
- mTOR
- PI3K/mTOR
- metastatic
- Triple Negative Breast Cancer (TNBC)
Last Updated
December 8, 2020