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

NCT01684215 | Completed Phase 2 Results

• 1 other identifier: A5481010
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 16

Brief 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.

Conditions

Neoplasms; Breast Neoplasms

Keywords

Phase 1/2; PD-0332991; palbociclib; Cyclin Dependent Kinase 4/6 inhibitor; Japanese; solid tumors; breast cancer; A5481010

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1

  DLT was classified as per common terminology criteria for adverse events (CTCAE) version 4.0 as any of the events occurring during 28 days of Cycle 1,attributed to study drug:grade 4 neutropenia(for a duration of greater than \[\>\]7 days); febrile neutropenia (grade greater than or equal to \[\>=\]3 neutropenia,body temperature \>=38.5 degree Celsius);grade \>=3 thrombocytopenia with bleeding episode;grade 4 thrombocytopenia;grade \>=3 non-hematologic toxicity except grade 3 or more nausea, vomiting,electrolyte abnormality(if controllable by therapy);grade 3 QTc prolongation(\>500 millisecond \[msec\])persist after correction of reversible cause such as electrolyte abnormalities or hypoxia. Lack of hematologic recovery (platelets less than \[\<\]50,000/microliter \[mcL\],absolute neutrophil count \<1,000/mcL,hemoglobin \<8.0 gram/deciliter \[g/dL\]) or prolonged non hematologic toxicities that delays initiation of next dose by \>7 days;receipt of \<75 percent of planned dose in first cycle due to toxicity.

  Lead-in period (Day -7) up to Day 28 (Cycle 1)

• Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1

  A treatment related AE is any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event had a causal relationship with the treatment or usage. A 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. Relatedness was judged by investigator. AEs included both serious and non-serious adverse events.

  Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1

  AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An AE was considered treatment emergent if occurred for the first time after the start of study treatment or occurred prior to the start of treatment but increased in National Cancer Institute (NCI) CTCAE grade during study treatment period. AE severity was defined to be the maximum toxicity grade of the TEAEs experienced by the participants during the study. AE was assessed according to severity as: Grade 1 (mild AE), Grade 2 (moderate AE), Grade 3 (severe AE), Grade 4 (life-threatening consequences) and Grade 5 (death related to AE).

  Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)

• Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2

  PFS was defined as the time from first dose of study treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause in the absence of documented PD, whichever occurred first. PD was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.1-year PFS was defined as the percentage of participants without PFS events (PD or death due to any cause) at 12 months based on the Kaplan-Meier estimate. Percentage of participants with 1-year PFS with 90% confidence interval (CI) were reported.

  From initiation of treatment up to 12 months

Secondary Outcomes (37)

• Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2

  Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2

  Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days)

• Number of Participants With Clinically Significant Laboratory Abnormalities

  Part 1 Phase 1: Lead-in period (Day -7) up to 308 days; Part 2 Phase 1: Baseline (Day 1) up to 1673 days; Phase 2: Baseline (Day 1) up to 1526 days

• Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1

  Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

• AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1

  Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

Study Arms (3)

Single-agent PD-0332991

EXPERIMENTAL

Phase 1 Part 1

Drug: PD-0332991

PD-0332991 in combination with letrozole

EXPERIMENTAL

Phase 1 Part 2

Drug: PD-0332991; Drug: letrozole

PD-0332991 with letrozole

EXPERIMENTAL

Phase 2

Drug: PD-0332991; Drug: letrozole

Interventions

PD-0332991 DRUG

PD-0332991 (100 mg or 125 mg) will be orally administered once a day for 3 weeks followed by 1 week off treatment, in the morning on an empty stomach. Dose reduction of PD-0332991 by one (100 mg) or two (75 mg) dose level is permitted depending on treatment related toxicity.

Single-agent PD-0332991

letrozole DRUG

Letrozole, 2.5 mg, will be orally administered once a day in continuous daily dosing together with PD-0332991. Dose reduction of letrozole is not permitted, but dosing interruptions for letrozole-related toxicity are allowed as per investigator's medical judgement.

PD-0332991 in combination with letrozole

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (16)

Aichi Cancer Center Hospital

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, 003-0804, Japan

Location

Kumamoto Shinto General Hospital

Kumamoto, Kumamoto, 862-8655, Japan

Location

Saitama Cancer Center

Kita-adachi-gun, Saitama, 362-0806, Japan

Location

National Cancer Center Hospital

Chuo-Ku, Tokyo, 104-0045, Japan

Location

Chiba Cancer Center

Chiba, 260-8717, Japan

Location

National Hospital Organization Shikoku Cancer Center

Ehime, 791-0280, Japan

Location

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Hiroshima City Hiroshima Citizens Hospital

Hiroshima, 730-8518, Japan

Location

Hakuaikai Medical Corporation Sagara Hospital

Kagoshima, 892-0833, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Kumamoto City Hospital

Kumamoto, 862-8505, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Iwate Medical University Hospital

Numakunai, 020-8505, Japan

Location

National Hospital Organization Osaka National Hospital

Osaka, 540-0006, Japan

Location

Related Publications (3)

• Takahashi M, Masuda N, Nishimura R, Inoue K, Ohno S, Iwata H, Hashigaki S, Muramatsu Y, Umeyama Y, Toi M. Palbociclib-letrozole as first-line treatment for advanced breast cancer: Updated results from a Japanese phase 2 study. Cancer Med. 2020 Jul;9(14):4929-4940. doi: 10.1002/cam4.3091. Epub 2020 May 18.

  PMID: 32420697 DERIVED

• Masuda N, Mukai H, Inoue K, Rai Y, Ohno S, Mori Y, Hashigaki S, Muramatsu Y, Umeyama Y, Iwata H, Toi M. Neutropenia management with palbociclib in Japanese patients with advanced breast cancer. Breast Cancer. 2019 Sep;26(5):637-650. doi: 10.1007/s12282-019-00970-7. Epub 2019 May 24.

  PMID: 31127500 DERIVED

• Tamura K, Mukai H, Naito Y, Yonemori K, Kodaira M, Tanabe Y, Yamamoto N, Osera S, Sasaki M, Mori Y, Hashigaki S, Nagasawa T, Umeyama Y, Yoshino T. Phase I study of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in Japanese patients. Cancer Sci. 2016 Jun;107(6):755-63. doi: 10.1111/cas.12932. Epub 2016 May 11.

  PMID: 26991823 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Neoplasms; Breast Neoplasms

Interventions

palbociclib; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2012
• First Posted: September 12, 2012
• Study Start: October 19, 2012
• Primary Completion: March 4, 2016
• Study Completion: October 25, 2018
• Last Updated: November 23, 2020
• Results First Posted: May 2, 2017

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share

Locations

JP (16)