Phase 1
N=72
A Trial In Patients With Advanced Cancer And Leukemia
Neoplasms by Histologic Type
Bottom Line
View on ClinicalTrials.gov: NCT00878189 ↗Enrolled (actual)
72
Serious AEs
43.1%
Results posted
Nov 2019
Primary outcome: Primary: Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT) — 0; 0; 0; 1 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-03084014 (Drug)
- Age
- Pediatric, Adult, Older Adult · 16+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Jan 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT) |
0; 0; 0; 1; 0; 1 | — |
| PRIMARY Number of T-ALL/LBL Participants With First-Cycle DLT |
1 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) |
3; 3; 4; 7; 4; 23 | — |
| SECONDARY Number of Participants With TEAEs (Treatment-Related) |
2; 1; 2; 6; 4; 20 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) by Severity (by Maximum Common Terminology Criteria for Adverse Events [CTCAE] Grade) |
0; 0; 1; 1; 0; 1 | — |
| SECONDARY Number of Participants With TEAEs (Treatment-Related) by Severity (by Maximum CTCAE Grade) |
1; 0; 1; 1; 1; 6 | — |
| SECONDARY Number of Participants With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval |
0; 3; 2; 4; 2; 11 | — |
| SECONDARY Number of Participants With Laboratory Tests Abnormalities Meeting the Criteria of Potential Clinical Concern (Hematology and Chemistries, All Cycles) |
45; 8; 40; 8; 4; 5 | — |
| SECONDARY Maximum Observed Serum Concentration (Cmax) After a Single Dose on Cycle 1 Day 1 |
163; 368; 230; 691; 536; 943 | — |
| SECONDARY Dose-normalized Cmax [Cmax (dn)] After a Single Dose on Cycle 1 Day 1 |
8.1; 9.2; 2.9; 6.9; 4.1; 6.3 | — |
| SECONDARY Area Under the Time-Concentration Curve From Time 0 to the Dosing Interval (AUCtau) After a Single Dose on Cycle 1 Day 1 |
409; 1329; 1649; 2204; 2924; 3677 | — |
| SECONDARY Dose-normalized AUCtau [AUCtau (dn) ] After a Single Dose on Cycle 1 Day 1 |
20.4; 33.2; 20.6; 22.0; 22.5; 24.5 | — |
| SECONDARY Time to Reach Cmax (Tmax) After a Single Dose on Cycle 1 Day 1 |
1.0; 1.0; 2.0; 1.0; 2.5; 1.1 | — |
| SECONDARY Cmax After Multiple Dose on Cycle 1 Day 21 |
64.5; 381; 313; 867; 421; 1246 | — |
| SECONDARY Time to Reach Cmax (Tmax) After Multiple Dose on Cycle 1 Day 21 |
1.1; 1.0; 1.1; 1.0; 3.7; 1.1 | — |
| SECONDARY AUCtau After Multiple Dose on Cycle 1 Day 21 |
309.0; 2521; 1572; 4741; 3155; 6430 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) on Cycle 1 Day 21 |
2810; 516; 3353; 986; 2048; 801 | — |
| SECONDARY Serum Decay Half-Life (t1/2) After Multiple Dose on Cycle 1 Day 21 |
30.3; 22.6; 38.6; 34.2; 34.7; 25.3 | — |
| SECONDARY Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 |
64.8; 15.9; 50.9; 21.1; 41.2; 23.4 | — |
| SECONDARY Minimum Observed Serum Concentration (Cmin) After Multiple Dose on Cycle 1 Day 21 |
10.7; 126; 59.2; 232; 206; 266 | — |
| SECONDARY Average Serum Concentration (Cavg) at Steady State on Cycle 1 Day 21 |
25.7; 210; 131; 395; 263; 536 | — |
| SECONDARY Accumulation Ratio (Rac) on Cycle 1 Day 21 |
1.18; 1.60; 1.36; 2.49; 1.98; 2.29 | — |
| SECONDARY Dose-normalized AUCtau [AUCtau (dn)] After Multiple Dose on Cycle 1 Day 21 |
15.4; 63.0; 19.7; 47.4; 24.3; 42.9 | — |
| SECONDARY Dose-normalized Cmax [Cmax (dn)] After Multiple Dose on Cycle 1 Day 21 |
3.2; 9.6; 3.9; 8.7; 3.2; 8.3 | — |
| SECONDARY AUCtau in the Fasted State for Solid Tumor Participants |
2547; 9353 | — |
| SECONDARY AUCtau in the Fed State for Solid Tumor Participants |
3163; 5573 | — |
| SECONDARY Cmax in the Fasted State for Solid Tumor Participants |
795.1; 2334 | — |
| SECONDARY Cmax in the Fed State for Solid Tumor Participants |
862.3; 924.4 | — |
| SECONDARY Dose-normalized AUCtau [AUCtau(dn)] in the Fasted State for Solid Tumor Participants |
23.71 | — |
| SECONDARY Dose-normalized AUCtau [AUCtau(dn)] in the Fed State for Solid Tumor Participants |
22.54 | — |
| SECONDARY Dose-normalized Cmax [Cmax(dn)] in the Fasted State for Solid Tumor Participants |
6.56 | — |
| SECONDARY Dose-Normalized Cmax [Cmax(dn)] in the Fed State for Solid Tumor Participants |
5.22 | — |
| SECONDARY AUCtau on Cycle 2 Day 1 |
2784; 11870 | — |
| SECONDARY Dose-normalized AUCtau [AUCtau (dn)] on Cycle 2 Day 1 |
18.6; 54.0 | — |
| SECONDARY Cmax on Cycle 2 Day 1 |
834.6; 2640 | — |
| SECONDARY Dose-normalized Cmax [Cmax (dn)] on Cycle 2 Day 1 |
5.6; 12.0 | — |
| SECONDARY Tmax on Cycle 2 Day 1 |
2.00; 1.53 | — |
| SECONDARY Percentage of Solid Tumor Participants With Objective Response (OR) |
33.3; 0; 66.7; 0; 0; 5.6 | — |
| SECONDARY Time to Tumor Progression (TTP) for Solid Tumor Participants |
NA; 1.2; NA; 3.1; 4.3; 1.6 | — |
| SECONDARY Duration of Response (DR) for Solid Tumor Participants |
NA; NA; NA; NA; NA | — |
| SECONDARY Progression-Free Survival (PFS) for Solid Tumor Participants |
NA; 1.2; NA; 2.3; 4.3; 1.6 | — |
| SECONDARY Percentage of T-ALL/LBL Participants With OR |
12.5 | — |
| SECONDARY Relapse Free Survival (RFS) for T-ALL/LBL Participants |
— | — |
| SECONDARY Peripheral Blast Count Reduction (PBR) for T-ALL/LBL Participants |
— | — |
| SECONDARY Changes in Expression Levels of Notch 1 Target Genes in Tumor Biopsies for Solid Tumor Participants: Hairy and Enhancer of Split-4 (Hes4) Gene Expression Levels on Cycle 1 Day 21 Relative to That at Baseline |
0.9; 0.5 | — |
| SECONDARY Changes From Baseline in Expression Levels of Notch 1 Target Genes in Peripheral Blood for T-ALL/LBL Participants: Hes4 Gene Expression Levels on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 21 Relative to That at Baseline |
0.7; 0.3; 0.4; 2.0 | — |
| SECONDARY Changes in Expression Levels of Notch 1 Target Genes in Peripheral Blood for Solid Tumor Participants: Hes4 Gene Expression Level on Cycle 1 Day 8 and Cycle 1 Day 21 Relative to That at Baseline |
0.3; 0.1; 0.3; 0.0 | — |
| SECONDARY Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Peripheral Blood for T-ALL/LBL Participants |
— | — |
| SECONDARY Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Bone Marrow for T-ALL/LBL Participants |
— | — |
Summary
This is a phase 1, dose escalating study to determine the safety of PF-03084014 in patients with advanced cancer and leukemia
Eligibility Criteria
Inclusion Criteria
- Patients with advanced cancer that is resistant to standard therapy or for which no standard therapy is available
- Patients with acute T cell leukemia/lymphoblastic lymphoma that is resistant to standard therapy or for which no standard therapy is available
- Men and women >16 years old
Exclusion Criteria
- Prior treatment with a gamma secretase inhibitor for treatment of cancer
- Patients taking Tamoxifen
- Patients with active graft versus host disease
- Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
- Patients who are pregnant or breast feeding
- Patients with clinical evidence of central nervous system disease
Data sourced from ClinicalTrials.gov (NCT00878189). 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.