Phase 1 N=78 Treatment

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

Neoplasms

Bottom Line

View on ClinicalTrials.gov: NCT00940498 ↗

Enrolled (actual)

Serious AEs

36.4%

Results posted

Nov 2018

Primary outcome: Primary: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) — 4; 4; 4; 4 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 1
Interventions: PF-05212384 (also known as PKI-587) (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Pfizer
Primary completion: Aug 2011

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	4; 4; 4; 4; 42; 7	—
PRIMARY Number of Participants With Treatment-Emergent Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)	3; 3; 4; 4; 40; 7	—
PRIMARY Number of Participants With Laboratory Abnormalities	4; 3; 4; 3; 41; 7	—
PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs)	0; 0; 0; 0; 2; 5	—
PRIMARY Recommended Phase-2 Dose (RP2D)	154	—
SECONDARY Maximum Observed Plasma Concentration (Cmax) of PF-05212384: Single and Multiple Dose	714.1; 1674; 3317; 6508; 9988; 14730	—
SECONDARY Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-05212384: Single Dose	1149; 2367; 5741; 13090; 15780; 26550	—
SECONDARY Plasma Decay Half-Life (t1/2) of PF-05212384: Single and Multiple Dose	15.14; 17.34; 40.73; 35.95; 35.84; 33.33	—
SECONDARY Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-05212384: Single Dose	1238; 2485; 5881; 13280; 16250; 27210	—
SECONDARY Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-05212384: Single and Multiple Dose	1256; 2604; 5753; 13100; 15810; 26740	—
SECONDARY Number of Participants With Maximum Increase From Baseline in Corrected QT Interval	3; 3; 3; 3; 26; 6	—
SECONDARY 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	100.3; 103.1; 87.0; 91.1; 95.6; 96.7	—
SECONDARY 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	23.8; 10.2; 8.6; 5.3; 13.1; 18.2	—
SECONDARY 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	3.0; 3.0; 4.6; 3.6; 6.2; 5.0	—
SECONDARY Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 1	12.2; 17.2; 44.3; 36.2; 172.3; 224.2	—
SECONDARY Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 22	34.3; 38.5; 145.1; 231.4; -12.3; -5.8	—
SECONDARY Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue	NA; NA; 28; 28; NA; NA	—
SECONDARY Percentage of Participants With Objective Response (OR)	2.6	—

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00940498). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.