Clinical trial NCT02129205: A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors
Official title: A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Neoplasms
Breast Cancer
Keywords: solid tumors
triple negative breast cancer
PF-06650808
Phase 1
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2014-05-02
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Dose-limiting Toxicities (DLT) (Part 1)
timeFrame: Day 1 up to Day 21
measure: Percentage of Participants With Objective Response (Part 1 and Part 2)
timeFrame: Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 3 years
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 1 and Part 2)
timeFrame: 3 years
measure: Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Hematology) (Part 1 and Part 2)
timeFrame: 3 years
measure: Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Chemistries) (Part 1 and Part 2)
timeFrame: 3 years
measure: Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Urinalysis) (Part 1 and Part 2)
timeFrame: 3 years
measure: Number of Participants With Vital Signs Meeting Categorical Summarization Criteria (Part 1 and Part 2)
timeFrame: 3 years
measure: Maximum Observed Serum Concentration (Cmax) (Part 1 and Part 2)
timeFrame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) (Part 1 and Part 2)
timeFrame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) (Part 1 and Part 2)
timeFrame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4
measure: Clearance (CL) (Part 1 and Part 2)
timeFrame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1
measure: Volume of Distribution at Steady State (Vss) (Part 1 and Part 2)
timeFrame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1
measure: Terminal Elimination Half-Life (t1/2) (Part 1 and Part 2)
timeFrame: Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4
measure: Number of Participants With the Presence of Anti-PF-06650808 Antibodies (Part 1 and Part 2)
timeFrame: 3 years
measure: Progression Free Survival and Overall Survival (Part 2)
timeFrame: 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center, Drug Information Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Los Angeles
country: United States
facility: Westwood Bowyer Clinic
state: California
city: Santa Monica
country: United States
facility: Santa Monica - UCLA Medical Center & Orthopaedic Hospital
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Columbus
country: United States
facility: The Ohio State University James Cancer Hospital
state: Ohio
city: Columbus
country: United States
facility: The OSU Investigational Drug Services
state: Ohio
city: Columbus
country: United States
facility: The OSU Stephanie Spielman Comprehensive Breast Center
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Martha Morehouse Medical Plaza
state: Ohio
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC (START)
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.