Phase 1
Completed N=110
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)
Neoplasm
Source: ClinicalTrials.gov NCT01920061 ↗
Enrolled (actual)
110
Serious AEs
34.6%
Results posted
Oct 2021
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C — 0; 0; 0; 0 Participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Percentage of Participants With Objective Response - Arm B Expansion |
40.0; 33.3 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion |
0; 0; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology |
0; 1; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation |
4; 4; 3; 2; 5; 2 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry |
3; 4; 2; 2; 5; 3 | — |
| SECONDARY Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Urinalysis |
1; 2; 1; 1; 2; 3 | — |
| SECONDARY Number of Participants With Vital Signs Data Meeting Pre-defined Criteria |
1; 2; 0; 3; 1; 0 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C) |
6455; 9539; 12090; 7128; 12420; 4522 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
11340; 10690 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A) |
8032; 8095; 10380; 11110; 10860 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B) |
10670; 7830; 6273; 9619; NA; 18730 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C) |
6739; NA; 6328; 8547; NA | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
9027; 14670 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A) |
946.7; 2451; 2528; 1529; 1058 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A) |
1840; 695.9; 2457; 1424; 1300 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B) |
3397; 3950; 3014; 4041; 3337; 3474 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B) |
3867; 4201; 3205; 4086; 3130; 3665 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C) |
41.04; 76.24; 34.17; 49.90 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C) |
52.38; NA; 33.64; 48.10 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C) |
NA; 12530; 15270; NA; 18710; 6756 | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A) |
10420; 15110; 15520; 14540; 15890 | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B) |
14620; 12690; NA; 18920; NA; 38850 | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C) |
10870; NA; 9977; 15910; NA | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
20180; 24480 | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
25250; 31160 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A) |
1418; 2748; 2111; 1594; 1280 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A) |
2921; 2175; NA; 1415; 1383 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B) |
50210; 50860; 44240; 48870; 42910; 46560 | — |
| SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B) |
59390; 62990; NA; 56170; 52940; 53470 | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C) |
818.8; 1604; 697.0; 1040 | — |
| SECONDARY Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C) |
1069; NA; 703.8; NA | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C) |
0.500; 0.500; 0.500; 0.550; 0.500; 0.584 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A) |
0.517; 0.500; 0.500; 0.517; 0.542 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B) |
0.500; 0.500; 0.550; 0.500; 0.675; 0.517 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C) |
0.500; NA; 0.500; 0.500; NA | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A) |
1.12; 1.00; 1.00; 1.02; 1.05 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A) |
1.06; 1.34; 1.03; 1.02; 1.13 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B) |
2.08; 2.12; 2.10; 2.00; 2.05; 2.01 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B) |
2.05; 2.00; 2.00; 2.00; 2.00; 2.02 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C) |
4.08; 6.00; 6.00; 5.97 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C) |
6.04; NA; 6.00; 5.42 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
0.517; 0.600 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
0.517; 0.500 | — |
| SECONDARY Mean Serum Biomarkers for Glucose - Baseline |
106.80; 95.07; 99.56; 100.97; 97.00; 124.51 | — |
| SECONDARY Mean Serum Biomarkers for Glucose - End of Treatment |
120.00; 99.84; 96.13; 108.11; 97.50; 136.91 | — |
| SECONDARY Mean Serum Biomarkers for Insulin - Baseline |
10.93; 155.14; 28.61; 710.50; 11.53; 12.65 | — |
| SECONDARY Mean Serum Biomarkers for Insulin - End of Treatment |
19.17; 318.62; 22.34; 832.87; 18.26; 13.73 | — |
| SECONDARY Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline |
7.92; 7.00; 7.27; 6.65; 5.13; 8.03 | — |
| SECONDARY Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment |
NA; 8.39; 7.70; 6.74; NA; 8.42 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Breast Cancer - Arms A and C |
0; 0; 33.3; 40.0; 0; 0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Non-Small Cell Lung Cancer - Arms A, B and C |
0; 0; 0; 14.3; 80.0; 25.0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Prostate Cancer - Arm A |
0; 66.7; 0; 33.3; 0; 100.0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Ovarian Cancer - Arm B |
0; 100.0; 0; 100.0; 0; 100.0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Transitional Cell Carcinoma - Arm B |
0; 28.6; 0; 71.4; 0; 100.0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Triple Negative Breast Cancer - Arm B |
0; 38.5; 0; 38.5; 0; 100.0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Head and Neck Cancer - Arm C |
0; 10.0; 0; 90.0; 0; 100.0 | — |
| SECONDARY Percentage of Participants With BRAF and KRAS Mutations in Population of Oesophageal Carcinoma - Arm C |
0; 42.9; 0; 42.9; 0; 100.0 | — |
| SECONDARY Number of Participants With Maximum Increase From Baseline in Corrected QT (QTc) Interval |
4; 5; 3; 1; 4; 4 | — |
| SECONDARY Number of Participants With Maximum Corrected QT (QTc) Interval Meeting Pre-defined Criteria |
3; 3; 3; 3; 3; 1 | — |
| SECONDARY Percentage of Participants With Objective Response - Arm A |
0; 40; 0; 66.7; 20 | — |
| SECONDARY Percentage of Participants With Objective Response - Arm B |
0.0; 33.3; 66.7; 66.7; 33.3; 20.0 | — |
| SECONDARY Percentage of Participants With Objective Response - Arm C |
20.0; 25.0; 14.3; 0; 33.3 | — |
| SECONDARY Clinical Benefit Response Rate - Arm B Expansion |
60.0; 50.0 | — |
| SECONDARY Duration of Response - Arm B Expansion |
6.9; NA | — |
| SECONDARY Progression Free Survival - Arm B Expansion |
4.8; 8.5 | — |
| SECONDARY Mean Observed Score Values for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion |
64.58; 58.33; 50.00; 50.00; 53.12; 56.82 | — |
| SECONDARY Mean Change From Baseline for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion |
-16.67; -9.17; -11.46; -1.52; -14.28; -7.14 | — |
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.
Data sourced from ClinicalTrials.gov (NCT01920061). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.