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NeoplasmsPhase 1B2151001NCT00940498

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

A Phase 1 study testing PF-05212384 (also known as PKI-587) in people with Neoplasms, run by Pfizer at 9 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Neoplasms
What is being tested?
PF-05212384 (also known as PKI-587)
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
9 sitesin 3 countries
Study dates
Jan 2010to Oct 2012
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

9 sites in 3 countries.

9 sites in 3 countries

United States7 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana-Farber Cancer Insitute

    Boston, Massachusetts, 02215

  • Sarah Cannon Research Institute, Tennessee Oncology, PLLC

    Nashville, Tennessee, 37203-1632

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10022

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

Spain1 site

  • Hospital General Vall D'Hebron

    Barcelona, 08035

Other trials in Spain

United Kingdom1 site

  • King's College London

    London, England, SE1 9RT

Other trials in United Kingdom

About this study

Official title: A Phase 1 Study Of Pf-05212384 (Also Known As Pki-587) Administered As An Intravenous Infusion To Patients With Solid Tumors

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
Being tested
PF-05212384 (also known as PKI-587)
Keywords
Phase 1, Dose Finding, Solid Tumors, Tumors, PF-05212384
Medical subject headings
Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Intravenous dosing once weekly infusion

Study groups in NCT00940498
Study groupRoleWhat they receive
1ExperimentalPF-05212384 (also known as PKI-587)
Receives: Drug: PF-05212384 (also known as PKI-587)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

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

  2. 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.

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

  3. 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]).

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

  4. 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.

    Measured: Baseline up to Day 28

  5. Recommended Phase-2 Dose (RP2D)

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

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

Secondary outcomes (13)

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

    Measured: 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

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

    Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (Clast).

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

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

    Plasma decay half-life is the time measured for the plasma concentration of drug to decrease by one half.

    Measured: 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

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

    AUCinf= Area under the plasma concentration versus time curve (AUC) from time zero (predose) to extrapolated infinite time (0 - inf).

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

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

    Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 168 hours (1 Week). For Cycle 2, the last PK sample for parameter calculations was on 120 hours after the Day 1 dose, however AUCtau was extrapolated to 168 hours using t1/2.

    Measured: 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

  6. Number of Participants With Maximum Increase From Baseline in Corrected QT Interval

    Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Number of Participants with maximum increase from baseline in QTcB and QTcF of < 30 msec, between <=30 to <60 msec and >=60 were reported.

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

  7. 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

    Measured: 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)

  8. 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

    Measured: 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)

  9. 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

    Measured: 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)

  10. Change From Baseline in Hair Follicle Biopsy Biomarkers at Cycle 1 Day 1

    Analysis of hair follicles was conducted using a Reverse Phase Microarrays (RPMA) assay. Phosphoprotein biomarkers measured were pAkt S473, pAkt T308, pStat3 (Y705), Ki-67, and pPRAS40 (T246).

    Measured: Baseline, 2, 3 and 72 hours (H) postdose on Day 1 of Cycle 1

  11. Change From Baseline in Fresh Tumor Biopsy Biomarkers at Cycle 1 Day 22

    Tumor biopsies were taken from participants of reporting arm PF-05212384 154 mg dose level at baseline and at Cycle 1/Day 22. Biopsies were fixed in optimal cutting temperature compound and analyzed via RPMA. The biomarkers tested were phosphorylated versions of the proteins: AKT S473, AKT T308, FKHR T24 / FKHR1 T32, and STAT3. This outcome measure was planned to be analyzed only for the reporting arm Part 1 and 2: PF-05212384 154 mg, as pre-specified in protocol.

    Measured: Baseline, Day 22 of Cycle 1

  12. Number of Participants With Mutation, Deletion, Amplification in Phosphatidylinositol 3-kinase (PI3K) Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue

    Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were PIK3CA and phosphatase and tensin homolog (PTEN) by immunohistochemistry.

    Measured: Baseline

  13. Percentage of Participants With Objective Response (OR)

    Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). Percentage of participants with objective response were reported.

    Measured: Baseline until disease progression or death due to any cause (up to Cycle 14 [each cycle 28 days])

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jul 2009 (estimated)
  2. Study startJan 2010
  3. Primary completionAug 2011
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Masking
None (open label)
Enrolment
78 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00940498
Sponsor's protocol ID
B2151001
Other IDs
3265K1-1002, 2009-012379-85, 2009
Acronym
B2151001
Status last verified
Feb 2018
First submitted
14 Jul 2009
Last updated
2 Nov 2018
Data monitoring committee
No

Publications

  • 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.

    PubMed 25652454

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing PF-05212384 (also known as PKI-587) in people with Neoplasms, run by Pfizer at 9 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) (time frame: Baseline up to Cycle 14 (each cycle is 28 days)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00940498, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2018.

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