Study of PF-05212384 (Also Known as PKI-587)Administered Intravenously To Subjects With Solid Tumors

NCT00940498 | Completed Phase 1 Results

• 3 other identifiers: B21510013265K1-10022009-012379-85
• Study Type: interventional
• Target: 78
• Locations: 3 countries
• Sites: 9

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.

Conditions

Neoplasms

Keywords

Phase 1; Dose Finding; Solid Tumors; Tumors; PF-05212384

Outcome Measures

Primary Outcomes (5)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)

  An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Treatment-emergent were events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

  Baseline up to Cycle 14 (each cycle is 28 days)

• Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)

  Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An 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. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.

  Baseline up to Cycle 14 (each cycle is 28 days)

• Number of Participants With Laboratory Abnormalities

  Criteria for laboratory test abnormality: hematology (hemoglobin \[less than {\<} 0.8\*lower limit of normal {LLN}\], platelets \[\<0.5\*LLN or greater than {\>} 1.75\*upper limit of normal {ULN}\], white blood cells \[\<0.6\*LLN or \>1.5\*ULN\], lymphocytes \[\<0.8\*LLN or \>1.2\*ULN\], total neutrophils \[\<0.8\*LLN or \>1.2\*ULN\], basophils, eosinophils, monocytes \[\>1.2\*ULN\]); coagulation \[partial thromboplastin time, prothrombin (PT), PT international ratio \[\>1.1\*ULN\]); liver function (total bilirubin \[\>1.5\*ULN\], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase \[\>0.3\*ULN\], total protein, albumin \[\<0.8\*LLN or \>1.2\*ULN\]).

  Baseline up to Cycle 14 (each cycle is 28 days)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: Grade 3 nonhematologic AE (including nausea, vomiting, or diarrhea despite optimal therapy; or greater than or equal to \[\>=\] grade 3 asthenia \>2 days; or fasting serum glucose \>250 milligrams per deciliter (mg/dL) despite optimal therapy); \>=Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia lasting more than 7 days; Febrile neutropenia; other Grade 4 hematologic AE; delay of treatment \>2 consecutive weeks due to toxicity. Grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

  Baseline up to Day 28

• Recommended Phase-2 Dose (RP2D)

  RP2D of PF-05212384 was determined based on the safety profile including laboratory and clinical assessments and pharmacodynamics findings.

  Baseline up to Cycle 14 (each cycle is 28 days)

Secondary Outcomes (13)

• Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose

  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

• Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose

  Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1

• Plasma Decay Half-Life (t1/2) of PF-05212384: Single and Multiple Dose

  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

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-05212384: Single Dose

  Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1

• Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05212384: Single and Multiple Dose

  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

Study Arms (1)

1

EXPERIMENTAL

PF-05212384 (also known as PKI-587)

Drug: PF-05212384 (also known as PKI-587)

Interventions

PF-05212384 (also known as PKI-587) DRUG

Intravenous dosing once weekly infusion

1

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Pfizer: lead

Study Sites (9)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Insitute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10022, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute, Tennessee Oncology, PLLC

Nashville, Tennessee, 37203-1632, United States

Location

Hospital General Vall D'Hebron

Barcelona, 08035, Spain

Location

King's College London

London, England, SE1 9RT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 25652454 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Neoplasms

Interventions

gedatolisib

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
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2009
• First Posted: July 16, 2009
• Study Start: January 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: October 1, 2012
• Last Updated: November 2, 2018
• Results First Posted: November 2, 2018

Record last verified: 2018-02

Locations

ES (1); US (7); GB (1)