NCT02129205

Brief Summary

To assess the safety and tolerability at increasing dose levels of PF-06650808 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jun 2014

Typical duration for phase_1

Geographic Reach
1 country

11 active sites

Status
terminated

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 30, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 2, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

June 1, 2014

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2017

Completed
1.7 years until next milestone

Results Posted

Study results publicly available

March 29, 2019

Completed
Last Updated

March 29, 2019

Status Verified

December 1, 2018

Enrollment Period

3.1 years

First QC Date

April 30, 2014

Results QC Date

June 12, 2018

Last Update Submit

December 21, 2018

Conditions

Keywords

solid tumorstriple negative breast cancerPF-06650808Phase 1

Outcome Measures

Primary Outcomes (2)

  • Number of Participants With Dose-limiting Toxicities (DLT) (Part 1)

    Severity of AEs (adverse events ) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the purpose of dose escalation, any of the following AEs which were not considered related to disease progression occurring in the first cycle of treatment (21 days) were classified as DLTs: 1) Hematologic: Grade 4 neutropenia lasting \>7 days; Febrile neutropenia; Grade\>=3 neutropenia with infection; Any grade thrombocytopenia associated with clinically significant or life threatening bleeding; Grade 4 thrombocytopenia \>=72 hours or platelets\<=10,000/mm3 regardless of duration. 2) Non hematologic: Grade\>=3 toxicities except those that had not been maximally treated; Delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression. 3) clinically important or persistent toxicities may have been considered a DLT following review by the Sponsor and the investigators.

    Day 1 up to Day 21

  • Percentage of Participants With Objective Response (Part 1 and Part 2)

    Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant achieved complete response (CR) if both target and non-target lesions achieved CR, no new lesions; achieved partial response (PR) if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: \>= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits. The overall objective response was defined as confirmed CR and PR.

    Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 3 years

Secondary Outcomes (13)

  • Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 1 and Part 2)

    3 years

  • Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Hematology) (Part 1 and Part 2)

    3 years

  • Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Chemistries) (Part 1 and Part 2)

    3 years

  • Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Urinalysis) (Part 1 and Part 2)

    3 years

  • Number of Participants With Vital Signs Meeting Categorical Summarization Criteria (Part 1 and Part 2)

    3 years

  • +8 more secondary outcomes

Study Arms (1)

PF-06650808

EXPERIMENTAL
Drug: PF-06650808

Interventions

Dose Escalation Phase \[Part 1\] - PF-06650808 will be administered at doses starting at 0.2 mg/kg. Increases in dose will continue until MTD is determined.

PF-06650808

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available
  • Previously treated metastatic triple negative breast cancer that expresses Notch3 with at least one measurable lesion
  • Adequate bone marrow, renal and liver function

You may not qualify if:

  • Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of starting study treatment
  • Patients with known symptomatic brain metastases requiring steroids
  • Prior treatment with a compound of the same mechanism

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

Ronald Reagan UCLA Medical Center, Drug Information Center

Los Angeles, California, 90095, United States

Location

Ronald Reagan UCLA Medical Center

Los Angeles, California, 90095, United States

Location

UCLA Hematology/Oncology

Los Angeles, California, 90095, United States

Location

Westwood Bowyer Clinic

Los Angeles, California, 90095, United States

Location

Santa Monica - UCLA Medical Center & Orthopaedic Hospital

Santa Monica, California, 90404, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

The Ohio State University James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

The OSU Investigational Drug Services

Columbus, Ohio, 43210, United States

Location

The OSU Stephanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

Location

The Ohio State University Martha Morehouse Medical Plaza

Columbus, Ohio, 43221, United States

Location

South Texas Accelerated Research Therapeutics, LLC (START)

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

  • Rosen LS, Wesolowski R, Baffa R, Liao KH, Hua SY, Gibson BL, Pirie-Shepherd S, Tolcher AW. A phase I, dose-escalation study of PF-06650808, an anti-Notch3 antibody-drug conjugate, in patients with breast cancer and other advanced solid tumors. Invest New Drugs. 2020 Feb;38(1):120-130. doi: 10.1007/s10637-019-00754-y. Epub 2019 Mar 18.

Related Links

MeSH Terms

Conditions

NeoplasmsBreast NeoplasmsTriple Negative Breast Neoplasms

Interventions

PF-06650808

Condition Hierarchy (Ancestors)

Neoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Limitations and Caveats

The study was prematurely terminated as a business decision prior to the start of the dose expansion stage.

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer, Inc

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
Masking
NONE
Purpose
TREATMENT
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 30, 2014

First Posted

May 2, 2014

Study Start

June 1, 2014

Primary Completion

July 1, 2017

Study Completion

July 1, 2017

Last Updated

March 29, 2019

Results First Posted

March 29, 2019

Record last verified: 2018-12

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