Last reviewed · How we verify

NCT01684215

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

Completed Phase 2 Results posted Last updated 23 November 2020
What this trial tests

Phase 2 trial testing PD-0332991 in Neoplasms in 61 participants. Completed in 25 October 2018.

Timeline
19 October 2012
Primary endpoint
4 March 2016
25 October 2018

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Maskingnone
Primary purposetreatment
Enrollment61
Start date19 October 2012
Primary completion4 March 2016
Estimated completion25 October 2018
Sites16 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

20 and older, any sex, with Neoplasms or Breast Neoplasms. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Dose Limiting Toxicities (DLT): Part 1 Phase 1 Primary · Lead-in period (Day -7) up to Day 28 (Cycle 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

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort1
PD-0332991 125 mg: Dose Escalation Cohort1
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Part 2 Phase 1 Primary · Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)

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.

AEs
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort6
SAEs
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort2
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) By Severity: Part 2 Phase 1 Primary · Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days)

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 1
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort0
Grade 2
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort0
Grade 3
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort4
Grade 4
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort2
Grade 5
GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort0
Percentage of Participants With 1 Year Progression Free Survival (PFS): Phase 2 Primary · From initiation of treatment up to 12 months

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

GroupValue95% CI
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort75.662.4 – 84.7
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Phase 1 (Part 1) and Phase 2 Secondary · 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)

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.

AEs
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort6
PD-0332991 125 mg: Dose Escalation Cohort5
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort42
SAEs
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort0
PD-0332991 125 mg: Dose Escalation Cohort0
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort2
Number of Participants With Treatment-Emergent Adverse Events (AEs) By Severity: Phase 1 (Part 1) and Phase 2 Secondary · 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)

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 NCI CTCAE version 4.0 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-t

Grade 1
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort0
PD-0332991 125 mg: Dose Escalation Cohort1
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort0
Grade 2
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort0
PD-0332991 125 mg: Dose Escalation Cohort1
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort2
Grade 3
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort4
PD-0332991 125 mg: Dose Escalation Cohort3
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort29
Grade 4
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort2
PD-0332991 125 mg: Dose Escalation Cohort1
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort10
Grade 5
GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort0
PD-0332991 125 mg: Dose Escalation Cohort0
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort1
Number of Participants With Clinically Significant Laboratory Abnormalities Secondary · 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

Abnormality criteria: hemoglobin: \<0.8\*lower limit of normal \[LLN\], platelets: \<0.5\*LLN or \>1.75\*upper limit of normal \[ULN\], leukocytes: \<0.6\*LLN or \>1.5\*ULN, lymphocytes, total neutrophils: \<0.8\*LLN or \>1.2\*ULN, basophils, eosinophil,monocytes: \>1.2\*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GT): \>0.3\*ULN, total protein, albumin: \<0.8\*LLN or \>1.2\*ULN, total bilirubin, direct bilirubin: \>1.5\*ULN; blood urea nitrogen, creatinine: \>1.3\*ULN, uric acid: \>1.2\*ULN; sodium: \<0.95\*LLN or \>1.05\*ULN,

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort6
PD-0332991 125 mg: Dose Escalation Cohort6
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort6
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort40
Area Under the Plasma Concentration Time Curve Over Dosing Interval (AUCtau) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 Secondary · Multiple dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24 hours post-dose on Cycle 1 Day 8

AUCtau is area under the plasma concentration-time curve over dosing interval which is calculated by log-linear trapezoidal method.

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort1276± 45
PD-0332991 125 mg: Dose Escalation Cohort2838± 43
AUCtau Dose Normalized to 125 Milligram (mg) of PD-0332991 Following Multiple Dose: Part 1 Phase 1 Secondary · 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 mg is area under the plasma concentration-time curve over dosing interval dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort1595± 45
PD-0332991 125 mg: Dose Escalation Cohort2838± 43
Area Under the Plasma Concentration-Time Curve From 0 to Time 24 Hours (AUC24) of PD-0332991 Following Single Dose: Part 1 Phase 1 Secondary · Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)

AUC24 is area under the plasma concentration-time curve from 0 to time 24 hours which is calculated by log-linear trapezoidal method.

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort547.5± 19
PD-0332991 125 mg: Dose Escalation Cohort1322± 42
AUC24 Dose Normalized to 125 mg of PD-0332991 Following Single Dose: Part 1 Phase 1 Secondary · Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12 and 24 hours post-dose in Lead-in period (Day -7)

AUC24 Dose Normalized to 125 mg is area under the plasma concentration-time curve from 0 to time 24 hours dose normalized to 125 mg which is calculated by log-linear trapezoidal method.

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort684.5± 19
PD-0332991 125 mg: Dose Escalation Cohort1322± 42
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of PD-0332991 Following Single Dose: Part 1 Phase 1 Secondary · Single dose: 0 hour (pre-dose), 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose in Lead-in period (Day -7)

AUCinf is area under the plasma concentration-time curve from 0 to infinity which is calculated by log-linear trapezoidal method.

GroupValue95% CI
PD-0332991 100 mg: Dose Escalation Cohort1039± 32
PD-0332991 125 mg: Dose Escalation Cohort2483± 49

Adverse events — posted to ClinicalTrials.gov

Time frame: Part 1 Phase 1: Lead-in period (Day -7) up to 28 days after last dose of study drug (up to 308 days), Part 2 Phase 1: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1673 days), Phase 2: Baseline (Day 1) up to 28 days after last dose of study drug (up to 1526 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

PD-0332991 100 mg: Dose Escalation Cohort
Serious: 0/6 (0%)
Deaths:
PD-0332991 125 mg: Dose Escalation Cohort
Serious: 0/6 (0%)
Deaths:
PD-0332991 125 mg+ Letrozole 2.5 mg: MTD Cohort
Serious: 2/6 (33%)
Deaths:
PD-0332991 125 mg+ Letrozole 2.5 mg: Expanded Cohort
Serious: 4/42 (10%)
Deaths:

Serious adverse events (9 terms)

ReactionSystemPD-0332991 100 mg: Dose Es…PD-0332991 125 mg: Dose Es…PD-0332991 125 mg+ Letrozo…PD-0332991 125 mg+ Letrozo…
Gastrointestinal perforationGastrointestinal disorders
Febrile NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
MalaiseGeneral disorders
Cerebral HaemorrhageNervous system disorders
DizzinessNervous system disorders
Subarachnoid HaemorrhageNervous system disorders
Supraventricular tachycardiaCardiac disorders
OsteoarthritisMusculoskeletal and connective tissue disorders
Other adverse events (116 terms — click to expand)

ReactionSystemPD-0332991 100 mg: Dose Es…PD-0332991 125 mg: Dose Es…PD-0332991 125 mg+ Letrozo…PD-0332991 125 mg+ Letrozo…
Neutrophil count decreasedInvestigations
StomatitisGastrointestinal disorders
White blood cell count decreasedInvestigations
NasopharyngitisInfections and infestations
ConstipationGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
MalaiseGeneral disorders
FallInjury, poisoning and procedural complications
Platelet count decreasedInvestigations
NeutropeniaBlood and lymphatic system disorders
AlopeciaSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
PharyngitisInfections and infestations
HeadacheNervous system disorders
Upper respiratory tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
HypertensionVascular disorders
LeukopeniaBlood and lymphatic system disorders
CheilitisGastrointestinal disorders
Influenza like illnessGeneral disorders
DiarrhoeaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Musculoskeletal stiffnessMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders
Angular cheilitisInfections and infestations
CellulitisInfections and infestations
ConjunctivitisInfections and infestations
MyalgiaMusculoskeletal and connective tissue disorders
PalpitationsCardiac disorders
Dental cariesGastrointestinal disorders
Pain in extremityMusculoskeletal and connective tissue disorders
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Gastrointestinal perforation, Febrile Neutropenia, Vomiting, Malaise, Cerebral Haemorrhage, Dizziness, Subarachnoid Haemorrhage, Supraventricular tachycardia.

Data from ClinicalTrials.gov NCT01684215 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Cyclin D1, cancer progression, and opportunities in cancer treatment.
    Qie S, Diehl JA. · · 2016 · cited 527× · PMID 27695879 · DOI 10.1007/s00109-016-1475-3
  2. Recent advances of highly selective CDK4/6 inhibitors in breast cancer.
    Xu H, Yu S, Liu Q, Yuan X, et al · · 2017 · cited 118× · PMID 28438180 · DOI 10.1186/s13045-017-0467-2
  3. Clinical potential of novel therapeutic targets in breast cancer: CDK4/6, Src, JAK/STAT, PARP, HDAC, and PI3K/AKT/mTOR pathways.
    Hosford SR, Miller TW. · · 2014 · cited 109× · PMID 25206307 · DOI 10.2147/pgpm.s52762
  4. The application and prospect of CDK4/6 inhibitors in malignant solid tumors.
    Du Q, Guo X, Wang M, Li Y, et al · · 2020 · cited 105× · PMID 32357912 · DOI 10.1186/s13045-020-00880-8
  5. Mechanisms of resistance in estrogen receptor positive breast cancer: overcoming resistance to tamoxifen/aromatase inhibitors.
    Mills JN, Rutkovsky AC, Giordano A. · · 2018 · cited 99× · PMID 29719270 · DOI 10.1016/j.coph.2018.04.009
  6. Phase I study of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, in Japanese patients.
    Tamura K, Mukai H, Naito Y, Yonemori K, et al · · 2016 · cited 72× · PMID 26991823 · DOI 10.1111/cas.12932
  7. Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.
    Kaboli PJ, Imani S, Jomhori M, Ling KH. · · 2021 · cited 51× · PMID 34765318
  8. Cyclins and cyclin-dependent kinases: from biology to tumorigenesis and therapeutic opportunities.
    Zabihi M, Lotfi R, Yousefi AM, Bashash D. · · 2023 · cited 37× · PMID 35781526 · DOI 10.1007/s00432-022-04135-6

Verify or expand the search:

Other trials of PD-0332991

Trials testing the same drug.

Other recruiting trials for Neoplasms

Currently open trials in the same condition.

Other Pfizer trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT01684215.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing