NCT00721409|CompletedPhase 2Results

Study Of Letrozole With Or Without Palbociclib (PD-0332991) For The First-Line Treatment Of Hormone-Receptor Positive Advanced Breast Cancer

PHASE 1/2, OPEN-LABEL, RANDOMIZED STUDY OF THE SAFETY, EFFICACY, AND PHARMACOKINETICS OF LETROZOLE PLUS PD 0332991 (ORAL CDK 4/6 INHIBITOR) AND LETROZOLE SINGLE AGENT FOR THE FIRST-LINE TREATMENT OF ER POSITIVE, HER2 NEGATIVE ADVANCED BREAST CANCER IN POSTMENOPAUSAL WOMEN

Pfizer ClinicalTrials.gov

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2 other identifiers

A54810032008-002392-27

Study Type

interventional

Target

177

Locations

12 countries

Sites

104

Timeline

RegisteredJul 2008

StartedSep 2008

CompletionDec 2017

Brief Summary

The study is aimed to confirm that letrozole + PD 0332991 is safe and tolerable and to assess the effect of the combination on advanced breast cancer

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

177

participants targeted

Target at P75+ for phase_2 breast-cancer

Timeline

Completed

Started Sep 2008

Longer than P75 for phase_2 breast-cancer

Geographic Reach

12 countries

104 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.3 years study duration

First Submitted

Initial submission to the registry

July 22, 2008

Completed

2 days until next milestone

First Posted

Study publicly available on registry

July 24, 2008

Completed

2 months until next milestone

Study Start

First participant enrolled

September 15, 2008

Completed

5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 29, 2013

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

March 19, 2015

Completed

2.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 20, 2017

Completed

Last Updated

November 4, 2019

Status Verified

October 1, 2019

Enrollment Period

5.2 years

First QC Date

July 22, 2008

Results QC Date

March 4, 2015

Last Update Submit

October 21, 2019

Conditions

Breast Cancer

Keywords

hormone-receptor positive advanced breast cancer

Outcome Measures

Primary Outcomes (4)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs; All Causalities) at Phase 1
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Maximum treatment duration (approximately 55 months)
Number of Participants With Treatment-Related Adverse Events at Phase 1
An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Maximum treatment duration (approximately 55 months)
Number of Participants With Dose Limiting Toxicities at Phase 1
Dose limiting toxicity was defined as any of the following TEAEs occurring during the second cycle of treatment and possibly attributable to the combination of letrozole plus Palbociclib: 1. Grade 4 hematologic toxicity (including platelets \<25,000/μL, ANC \<500/μL). 2. Grade 3 neutropenia associated with a documented infection or fever ≥38.5°C. 3. Grade ≥3 non-hematologic toxicities, except those that have not been maximally treated (eg, nausea, vomiting, diarrhea, hypertension). 4. Delay by ≥1 week in receiving the next scheduled dose of either study treatment due to persisting treatment-related toxicities (platelet count \<50,000/μL; ANC \<1,000/μL; nonhematologic toxicities of Grade ≥3 severity). 5. Inability to deliver at least 80% of the planned Palbociclib or letrozole doses during Cycle 2 due to toxicity possibly attributable to the study treatment.
Cycle 2 (4 weeks)
Progression-Free Survival (PFS) at Phase 2 - Investigator Assessment
PFS was defined as the time from randomization (or the first dose of study treatment for non-randomized studies) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Weeks or Months) = (first event date minus randomization or the first dose date plus 1) divided by 7 (or 30.44 if in months). PFS is usually characterized by the median, 25% percentile,75% percentile and their 95% Confidence Intervals (CIs).
From randomization date to date of first documentation of progression or death (assessed up to 41 months)

Secondary Outcomes (27)

Objective Response Rate - Percentage of Participants With Confirmed Objective Tumor Response at Phase 1
From Baseline up to end of study (assessed up to 55 months)
Percentage of Participants With Clinical Benefit Response (CBR) at Phase 1
From Baseline up to end of study (assessed up to 55 months)
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC24) at Phase 1
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Maximum Observed Plasma Concentration (Cmax) at Phase 1
Cycle 1 Day 14, and Cycle 2 Day 14
Summary of Plasma Palbociclib Steady-state Pharmacokinetic Parameter Following Palbociclib Alone and in Combination With Letrozole: Time to Maximum Plasma Concentration (Tmax) at Phase 1
Cycle 1 Day 14, and Cycle 2 Day 14
+22 more secondary outcomes

Study Arms (2)

Arm A

EXPERIMENTAL

letrozole + PD 0332991

Drug: PD 0332991Drug: letrozole

Arm B

ACTIVE COMPARATOR

letrozole

Drug: letrozole

Interventions

PD 0332991DRUG

125 mg/d capsules orally for 3 out of 4 weeks in repeated cycles

Arm A

letrozoleDRUG

2.5 mg/d tablets orally on a continuous regimen

Arm A

Eligibility Criteria

Age18 Years+

Sexfemale(Gender-based eligibility)

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Inoperable estrogen receptor positive and HER2 negative breast cancer.
Postmenopausal status.
Tumor tissue (archived acceptable) available for biomarker studies. For Phase 2 Part 2 - CCND1 amplification and/or loss of p16 as determined by the central laboratory.
Acceptable bone marrow, liver and kidney function.

You may not qualify if:

Prior or concomitant treatment for advanced breast cancer.
Other major cancer in the past 3 years.
Important cardiovascular events in the past 6 months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead

Study Sites (104)

Central Hematology Oncology Medical group Inc.

Alhambra, California, 91801, United States

Location

UCLA Hematology/Oncology - Alhambra

Alhambra, California, 91801, United States

Location

CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

St. Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

UCLA West Medical Pharmacy (Drug Management Only)

Los Angeles, California, 90095-1772, United States

Location

UCLA West Medical Pharmacy

Los Angeles, California, 90095-1772, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095-6984, United States

Location

UCLA West Medical Pharmacy

Los Angeles, California, 90095-7349, United States

Location

Drug Management Only: UCLA West Medical Pharmacy