Phase 2
Completed N=12
A Study Of Oral Palbociclib (PD-0332991), A CDK4/6 Inhibitor, As Single Agent In Japanese Patients With Advanced Solid Tumors Or In Combination With Letrozole For The First-Line Treatment Of Postmenopausal Japanese Patients With ER (+) HER2 (-) Advanced Breast Cancer
Neoplasms · Breast Neoplasms
Source: ClinicalTrials.gov NCT01684215 ↗
Enrolled (actual)
12
Serious AEs
10.0%
Results posted
May 2017
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1 — 1; 1 Participants
Summary
This study is comprised of two portions: a Phase 1 portion and a Phase 2 portion. The Phase 1 portion is a single-country, non-randomized, open label, clinical trial which will evaluate the safety, tolerability, preliminary efficacy, and PK profile of PD-0332991 as a single agent in Japanese patients with advanced solid tumors, and PD-0332991 in combination with letrozole in the first-line treatment of Japanese patients with ER(+) HER2(-) ABC. The Phase 2 portion is a single-country, non-randomized, open-label, single-cohort, multi-center clinical trial to evaluate the efficacy and safety of PD-0332991 in combination with letrozole for the first-line treatment of postmenopausal Japanese patients with ER(+) HER2(-) ABC.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1 |
1; 1 | — |
| PRIMARY Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1 |
6; 2 | — |
| PRIMARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1 |
0; 0; 4; 2; 0 | — |
| PRIMARY Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2 |
75.6 | — |
| SECONDARY Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2 |
6; 5; 42; 0; 0; 2 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2 |
0; 1; 0; 0; 1; 2 | — |
| SECONDARY Number of Participants With Clinically Significant Laboratory Abnormalities |
6; 6; 6; 40 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 |
1276; 2838 | — |
| SECONDARY AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 |
1595; 2838 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1 |
547.5; 1322 | — |
| SECONDARY AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 |
684.5; 1322 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1 |
1039; 2483 | — |
| SECONDARY AUCinf Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 |
1296; 2483 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From 0 to Time of Last Measurable Concentration (AUClast) of PD-0332991 Following Single Dose: Part 1 Phase 1 |
971.7; 2396 | — |
| SECONDARY AUClast Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 |
1215; 2396 | — |
| SECONDARY Apparent Oral Clearance of PD-0332991: Part 1 Phase 1 |
96.43; 50.29; 78.43; 44.03 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Part 1 Phase 1 |
41.37; 104.1; 77.36; 185.5 | — |
| SECONDARY Cmax Dose Normalized to 125 mg of PD-0332991: Part 1 Phase 1 |
51.74; 104.1; 96.72; 185.5 | — |
| SECONDARY Pre-dose Plasma Concentration (Ctrough) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 |
35.51; 72.76 | — |
| SECONDARY Accumulation Ratio (Rac) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 |
2.060; 1.855 | — |
| SECONDARY Linearity (Rss) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 |
1.130; 1.105 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Part 1 Phase 1 |
5.02; 4.00; 4.02; 4.02 | — |
| SECONDARY Terminal Half-Life (t1/2) of PD-0332991: Part 1 Phase 1 |
25.72; 23.93; 23.75; 23.15 | — |
| SECONDARY Volume of Distribution (Vz/F) of PD-0332991 Following Single Dose: Part 1 Phase 1 |
3514; 1730 | — |
| SECONDARY Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991: Phase 2 |
1979 | — |
| SECONDARY Apparent Oral Clearance of PD-0332991: Phase 2 |
63.21 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) Of PD-0332991: Phase 2 |
124.7 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PD-0332991: Phase 2 |
4.90 | — |
| SECONDARY Pre-dose Plasma Concentration (Ctrough) of PD-0332991: Phase 2 |
59.75 | — |
| SECONDARY Percentage of Participants With Objective Response: Phase 1 |
0; 0; 0; 0; 0; 33.3 | — |
| SECONDARY Percentage of Participants With Objective Response: Phase 2 |
47.6 | — |
| SECONDARY Duration of Response (DOR): Part 2 Phase 1 |
1509; 1428 | — |
| SECONDARY Duration of Response (DOR): Phase 2 |
41.4 | — |
| SECONDARY Progression Free Survival (PFS): Part 2 Phase 1 |
1590; 1593; 1602; 36; 31; 1512 | — |
| SECONDARY Percentage of Participants With Disease Control (DC): Phase 2 |
85.7 | — |
| SECONDARY Overall Survival (OS): Phase 2 |
NA | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment |
106.46; -1.20; -2.22; -2.38; -4.62; -4.45 | — |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment |
80.22; -1.15; -1.34; -0.36; -3.56; -2.39 | — |
| SECONDARY Change From Baseline in Trial Outcome Index (TOI): Phase 2 at Day 1 of Cycle 2, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49 and End of Treatment |
71.52; -1.17; -2.20; -2.54; -3.63; -3.31 | — |
| SECONDARY Presence of Tumor Tissue Biomarker- Ki67: Phase 2 |
19; 23 | — |
| SECONDARY Presence of Tumor Tissue Biomarkers- Estrogen Receptor (ER) H-Score, Retinoblastoma (Rb) H-Score, B-cell Lymphoma-1 (BCL-1) H-Score, P16 H-Score: Phase 2 |
41; 41; 42; 41 | — |
Eligibility Criteria
Inclusion Criteria
Phase 1
- In Part 1, advanced solid tumor (except SCLC or retinoblastoma) proven histologically or cytologically at original diagnosis, that is refractory to standard therapy or for whom no standard of care therapy is available.
- In Part 2 and Phase 2, post menopausal women with proven diagnosis of ER-positive, HER2-negative adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease (including bone only disease) not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
- Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 or 1.
- Resolved acute effects of any prior therapy to baseline severity or Grade ≤1
Phase 2
- Adult women (≥ 20 years of age) with proven diagnosis of adenocarcinoma of the breast with evidence of locoregionally recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.
- Documentation of histologically or cytologically confirmed diagnosis of ER(+) breast cancer based on local laboratory results.
- Adequate blood cell counts, kidney function and liver function and and Eastern Cooperative Oncology Group [ECOG] score of 0 to 2.
Exclusion Criteria
Phase 1
- Active uncontrolled or symptomatic CNS metastases.
- Uncontrolled infection, unstable or sever intercurrent medical condition, or current drug or alcohol abuse
- Active or unstable cardiac disease or history of heart attack within 6 months
Phase 2
- HER2 positive tumor based on local laboratory results utilizing one of the sponsor approved assays.
- Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease.
- Prior neoadjuvant or adjuvant treatment with a non steroidal aromatase inhibitor (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment.
Data sourced from ClinicalTrials.gov (NCT01684215). 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.