Phase 1
N=47
A Study Of PF-04449913 In Select Hematologic Malignancies
Hematologic Malignancies
Bottom Line
View on ClinicalTrials.gov: NCT00953758 ↗Enrolled (actual)
47
Serious AEs
68.1%
Results posted
Apr 2024
Primary outcome: Primary: Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-04449913 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Sep 2012
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade |
0.0; 0.0; 25.0; 25.0; 12.5; 33.3 | — |
| SECONDARY Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Number of Participants With Laboratory Test Abnormalities |
3; 3; 4; 4; 8; 3 | — |
| SECONDARY Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21 |
0.1; 0.0; 0.0 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) on Lead-in |
32.9; 59.0; 247; 313; 746; 1418 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 |
45.4; 75.0; 249; 565; 871; 1621 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in |
2.0; 2.0; 1.0; 1.0; 2.0; 2.0 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 |
2.2; 1.0; 0.92; 1.0; 1.3; 2.2 | — |
| SECONDARY Apparent Oral Clearance (CL/F) on Lead-in |
7.61; 12.7; 5.63; 11.1; 9.13; 8.33 | — |
| SECONDARY Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 |
8.57; 13.3; 7.79; 6.52; 10.7; 5.33 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) on Lead-in |
262; 455; 265; 367; 292; 316 | — |
| SECONDARY Plasma Decay Half-life (t1/2) on Lead-in |
25.1; 25.1; 34.3; 23.3; 23.3; 26.5 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in |
657; 786; 3548; 3614; 8755; 14430 | — |
| SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 |
583; 753; 2566; 6134; 7482; 22520 | — |
| SECONDARY Average Plasma Concentration (Cavg) on Cycle 1 Day 21 |
24.3; 31.4; 107; 256; 312; 940 | — |
| SECONDARY Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 |
14.7; 18.9; 54.7; 162; 116; 360 | — |
| SECONDARY Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 |
15.1; 18.9; 67.8; 170; 120; 495 | — |
| SECONDARY Accumulation Ratio (Rac) |
1.4; 1.6; 1.6; 2.4; 1.4; 2.5 | — |
| SECONDARY Linearity Ratio (Rss) |
0.91; 1.1; 0.76; 1.6; 0.97; 2.1 | — |
| SECONDARY Renal Clearance on Cycle 1 Day 21 |
0.623; 1.36; 0.754; 0.385; 1.14; 0.403 | — |
| SECONDARY Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 |
352; 1027; 1933; 2357; 8524; 9066 | — |
| SECONDARY Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 |
7.03; 10.3; 9.68; 5.89; 10.7; 7.57 | — |
| SECONDARY Percentage of Participants With Objective Response (OR) |
28.6; 28.6; 32.1; 0; 0 | — |
| SECONDARY Time to Progression (TTP) |
NA; 10.12; 2.83; 3.75; NA | — |
| SECONDARY Duration of Response (DR) |
21.45; NA; 2.83; NA; NA | — |
| SECONDARY Progression-Free Survival (PFS) |
NA; 4.43; 2.83; 3.75; NA | — |
| SECONDARY Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) |
2; 3; 3; 4; 7; 2 | — |
| SECONDARY Number of Participants With Decrease From Baseline in QTcF Interval |
1; 2; 2; 1; 5; 2 | — |
| SECONDARY Number of Participants With Post-baseline QTcF Interval >= 500 Msec |
0; 0; 0; 0; 0; 0 | — |
Summary
This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select hematologic malignancies.
Eligibility Criteria
Inclusion Criteria
- Patients with select advanced hematologic malignancies who are refractory, resistant or intolerant to prior therapies. They may be newly diagnosed and previously untreated, but not eligible for standard treatment options, or for whom standard therapies are not anticipated to result in a durable response.
- ECOG performance status 0 to 2
- Adequate organ function
Exclusion Criteria
- Patients with active CNS disease
- Patient with active malignancy with the exception of basal cell carcinoma, non melanoma skin cancer, carcinoma in situ cervical or skin cancer
- Active GVHD other than Grade 1 skin involvement
- Known malabsorption syndrome
- Patient has an active, life threatening or clinically significant uncontrolled systemic infection
Data sourced from ClinicalTrials.gov (NCT00953758). 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.