Clinical trial NCT00940498: Study of PF-05212384 (Also Known as PKI-587)Administered Intravenously To Subjects With Solid Tumors
Official title: A Phase 1 Study Of Pf-05212384 (Also Known As Pki-587) Administered As An Intravenous Infusion To Patients With Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neoplasms
Keywords: Phase 1
Dose Finding
Solid Tumors
Tumors
PF-05212384
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2009-07-16
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: This is a two-part study of a compound called PF-05212384 (also known as PKI-587). The purpose of part 1 is to identify the Maximum Tolerated Dose (MTD) of PF-05212384 using a Continual Reassessment Method (CRM). Part 1 will include subjects with any solid tumor. In Part 2 two cohorts will be enrolled. One cohort will assess safety, tolerability and preliminary efficacy in 20 subjects at the MTD and will include subjects with breast cancer, ovarian cancer, endometrial cancer, colorectal cancer renal cancer or glioblastoma (a type of brain tumor). The other cohort will include 5 to 15 subjects with any type of tumor who consent to provide tumor biopsies while participating in the study.


Eligibility criteria: Inclusion Criteria:

* Pathologic diagnosis of any solid tumor
* Incurable cancer, with disease progression following at least 1 therapy with no further standard treatment available in the opinion of the investigator.
* At least 1 evaluable lesion per RECIST criteria

Exclusion Criteria:

* Clinically unstable primary or metastatic CNS tumors
* Subjects with known diabetes
* QTc interval greater than 470 ms.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to Cycle 14 (each cycle is 28 days)
measure: Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to Cycle 14 (each cycle is 28 days)
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to Cycle 14 (each cycle is 28 days)
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Baseline up to Day 28
measure: Recommended Phase-2 Dose (RP2D)
timeFrame: Baseline up to Cycle 14 (each cycle is 28 days)
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose
timeFrame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
measure: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose
timeFrame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1
measure: Plasma Decay Half-Life (t1/2) of PF-05212384: Single and Multiple Dose
timeFrame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-05212384: Single Dose
timeFrame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05212384: Single and Multiple Dose
timeFrame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1
measure: Number of Participants With Maximum Increase From Baseline in Corrected QT Interval
timeFrame: Baseline up to Cycle 14 (each cycle is 28 days)
measure: Change From Baseline in Serum Glucose at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment
timeFrame: Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)
measure: Change From Baseline in Serum Insulin at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment
timeFrame: Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)
measure: Change From Baseline in Serum C-peptide at Day 2 of Cycle 1, Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 and End of Treatment
timeFrame: Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)
measure: Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 1
timeFrame: Baseline, 2, 3 and 72 hours (H) postdose on Day 1 of Cycle 1
measure: Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 22
timeFrame: Baseline, Day 22 of Cycle 1
measure: Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue
timeFrame: Baseline
measure: Percentage of Participants With Objective Response (OR)
timeFrame: Baseline until disease progression or death due to any cause (up to Cycle 14 [each cycle 28 days])
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Insitute
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute, Tennessee Oncology, PLLC
state: Tennessee
city: Barcelona
country: Spain
facility: Hospital General Vall D'Hebron
city: London
country: United Kingdom
facility: King's College London
state: England
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Shapiro GI, Bell-McGuinn KM, Molina JR, Bendell J, Spicer J, Kwak EL, Pandya SS, Millham R, Borzillo G, Pierce KJ, Han L, Houk BE, Gallo JD, Alsina M, Brana I, Tabernero J. First-in-Human Study of PF-05212384 (PKI-587), a Small-Molecule, Intravenous, Dual Inhibitor of PI3K and mTOR in Patients with Advanced Cancer. Clin Cancer Res. 2015 Apr 15;21(8):1888-95. doi: 10.1158/1078-0432.CCR-14-1306. Epub 2015 Feb 4.