NCT00878189

Brief Summary

This is a phase 1, dose escalating study to determine the safety of PF-03084014 in patients with advanced cancer and leukemia

Trial Health

90
On Track

Trial Health Score

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

Enrollment
72

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jun 2009

Longer than P75 for phase_1

Geographic Reach
2 countries

10 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

First Submitted

Initial submission to the registry

April 6, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 8, 2009

Completed
3 months until next milestone

Study Start

First participant enrolled

June 25, 2009

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 10, 2013

Completed
3.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 22, 2016

Completed
3 years until next milestone

Results Posted

Study results publicly available

November 12, 2019

Completed
Last Updated

November 12, 2019

Status Verified

October 1, 2019

Enrollment Period

3.5 years

First QC Date

April 6, 2009

Results QC Date

October 30, 2017

Last Update Submit

October 21, 2019

Conditions

Neoplasms by Histologic Type

Keywords

Phase 1 dose escalation study in advanced solid tumor malignancy and leukemia

Outcome Measures

Primary Outcomes (2)

  • Number of Solid Tumor Participants With First-Cycle Dose-Limiting Toxicity (DLT)

    Any DLT event attributable to PF-03084014 during Cycle 1: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days or unable to deliver at least 80% of planned dose due to treatment-related toxicities; Grade 4 neutropenia \>7 days; febrile neutropenia; neutropenic infection; Grade \>=3 thrombocytopenia with bleeding

    Baseline to the end of Cycle 1 (Week 4)

  • Number of T-ALL/LBL Participants With First-Cycle DLT

    Any DLT attributable to PF-03084014 at 1st Cycle: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days; unable to deliver at least 80% of planned dose; absolute neutrophil count (ANC) \<1000/microliter (uL), or platelet count \<30,000/uL, or hemoglobin \<8 gram/deciliter (g/dL) in a bone marrow with \<5% blasts and no evidence of leukemia or abnormal dysplasia for \>42 days

    Baseline to the end of Cycle 1 (Week 4)

Secondary Outcomes (47)

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality)

    Baseline up to end of study (maximum of 84 months)

  • Number of Participants With TEAEs (Treatment-Related)

    Baseline up to end of study (maximum of 84 months)

  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (All Causality) by Severity (by Maximum Common Terminology Criteria for Adverse Events [CTCAE] Grade)

    Baseline up to end of study (maximum of 84 months)

  • Number of Participants With TEAEs (Treatment-Related) by Severity (by Maximum CTCAE Grade)

    Baseline up to end of study (maximum of 84 months)

  • Number of Participants With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval

    Baseline up to end of study (maximum of 84 months)

  • +42 more secondary outcomes

Study Arms (1)

1

EXPERIMENTAL
Drug: PF-03084014

Interventions

PF-03084014DRUG

10 mg, 50 mg or 100 mg tablets. Patients dosed from 20 mg - 500 mg, twice daily

Also known as: gamma secretase inhibitor
1

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients with advanced cancer that is resistant to standard therapy or for which no standard therapy is available
  • Patients with acute T cell leukemia/lymphoblastic lymphoma that is resistant to standard therapy or for which no standard therapy is available
  • Men and women \>16 years old

You may not qualify if:

  • Prior treatment with a gamma secretase inhibitor for treatment of cancer
  • Patients taking Tamoxifen
  • Patients with active graft versus host disease
  • Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
  • Patients who are pregnant or breast feeding
  • Patients with clinical evidence of central nervous system disease

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

University of Colorado Denver CTRC

Aurora, Colorado, 80045, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital Clinical Laboratory

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Ferber Cancer institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center / Wayne State University

Detroit, Michigan, 48201, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

DIPRTMNT CLIN Scienze RADIOL e Istocitopatologiche

Bologna, 40138, Italy

Location

Istituto di Ematologia Seragnoli

Bologna, 40138, Italy

Location

Related Publications (2)

  • Papayannidis C, DeAngelo DJ, Stock W, Huang B, Shaik MN, Cesari R, Zheng X, Reynolds JM, English PA, Ozeck M, Aster JC, Kuo F, Huang D, Lira PD, McLachlan KR, Kern KA, Garcia-Manero G, Martinelli G. A Phase 1 study of the novel gamma-secretase inhibitor PF-03084014 in patients with T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma. Blood Cancer J. 2015 Sep 25;5(9):e350. doi: 10.1038/bcj.2015.80. No abstract available.

    PMID: 26407235DERIVED

  • Tabares-Seisdedos R, Rubenstein JL. Inverse cancer comorbidity: a serendipitous opportunity to gain insight into CNS disorders. Nat Rev Neurosci. 2013 Apr;14(4):293-304. doi: 10.1038/nrn3464.

    PMID: 23511909DERIVED

Related Links

MeSH Terms

Conditions

Neoplasms by Histologic TypeLeukemia

Interventions

nirogacestat

Condition Hierarchy (Ancestors)

NeoplasmsHematologic DiseasesHemic and Lymphatic Diseases

Limitations and Caveats

Study components related to combination therapy with dexamethasone were removed due to operational/scientific reasons. Due to halting of T-AA/LBL participant's enrollment; limited number of evaluable participants, PBR and RFS data was not collected.

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 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 6, 2009

First Posted

April 8, 2009

Study Start

June 25, 2009

Primary Completion

January 10, 2013

Study Completion

November 22, 2016

Last Updated

November 12, 2019

Results First Posted

November 12, 2019

Record last verified: 2019-10

Data Sharing

IPD Sharing
Will not share

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

Locations

IT(2)US(8)