Pre-Operative Study of PF-4691502 With Letrozole Compared To Letrozole Alone In Patients With Early Breast Cancer

NCT01430585 | Terminated Phase 2 Results

• 1 other identifier: B1271003
• Study Type: interventional
• Target: 14
• Locations: 4 countries
• Sites: 5

Brief Summary

PF-04691502 is an inhibitor of PI3K and mTOR kinase. Published data support the hypothesis that a PI3K/mTOR antagonist in combination with letrozole might mitigate the intrinsic or acquired resistance to hormonal therapy and restore hormone sensitivity in high risk (high Ki-67) patient population of hormone-sensitive breast cancers. In addition, Ki-67, a marker of cellular proliferation, could be used to select those patients who benefit from treatment with a PI3K-pathway inhibitor.

Conditions

Early Breast Cancer (Phase 2); Advanced Breast Cancer (Phase 1b)

Keywords

Ki-67; postmenopausal early breast cancer; ER positive/HER2 negative early breast cancer

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 1B

  An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE: 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 treatment and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

  Phase 1B: Baseline up to 28 days after last administration of study treatment

• Change From Baseline in Ki-67 Percent Positive Tumor Cells in Biopsied Tumor Tissue at Week 6: Phase 2

  Nuclear proliferation marker Ki-67 was to be assessed by immunohistochemistry technique in all specimens.

  Phase 2: Baseline, Week 6

Secondary Outcomes (8)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs): Phase 2

  Phase 2: Baseline up to 28 days after last administration of study treatment

• Number of Participants With Clinically Significant Laboratory Tests Abnormalities: Phase 1B and 2

  Phase 1B: Baseline up to end of treatment (Week 34); Phase 2: Baseline up to Week 16 or early termination (ET)

• Number of Participants With Clinically Significant Abnormalities in Vital Signs: Phase 1B and 2

  Phase 1B: Baseline up to 28 days after last dose of study treatment (Week 34); Phase 2: Baseline up to Week 16 or ET

• Number of Participants With Clinically Significant Abnormalities in Corrected QT (QTc) Interval: Phase 1B

  Phase 1B: Baseline up to end of treatment (Week 34)

• Number of Participants With Objective Response (OR): Phase 1B and 2

  Phase 1B: Baseline, Week 12, end of treatment (Week 34); Phase 2: Baseline, Week 6, 16 or ET

Study Arms (3)

A

EXPERIMENTAL

Drug: PF-04691502

B

EXPERIMENTAL

Drug: PF-04691502 in combination with Letrozole

C

ACTIVE COMPARATOR

Drug: Letrozole

Interventions

PF-04691502 DRUG

PF-04691502 administered as single agent for 2 weeks. After this period, patients in this arm will take PF-04691502 in combination with Letrozole until Week 6. Beyond Week 6, if considered appropriate, patients can be treated with the combination for up to 10 additional weeks until breast surgery.

A

PF-04691502 in combination with Letrozole DRUG

PF-04691502 in combination with Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery.

B

Letrozole DRUG

Letrozole will be administered for 6 weeks. Beyond Week 6, if considered appropriate, patients can be treated for up to 10 additional weeks until breast surgery.

C

Eligibility Criteria

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

You may qualify if:

• Phase 1 - Postmenopausal women with diagnosis of breast cancer, metastatic disease or locally advanced disease / Estrogen Receptor positive and HER-2 negative / candidate to receive Letrozole
• Phase 2 - Postmenopausal women with newly diagnosed primary breast cancer / Estrogen Receptor positive and HER-2 negative / Ki-67 levels \>10% positive cells
• Phase 1 \& 2 - Glucose control, adequate bone marrow, liver, renal, and cardiac function

You may not qualify if:

• Inflammatory carcinoma / Prior therapy with an agent active on PI3K and/or mTOR / Significant gastrointestinal abnormalities, which may impair intake, transit or absorption of the study drugs / Current or anticipated need for food or drugs that are known inhibitors or inducers of CYP3A4

Sponsors & Collaborators

• Pfizer: lead

Study Sites (5)

Pfizer Investigational Site

Charleroi, 6000, Belgium

Location

Pfizer Investigational Site

Milan, 20132, Italy

Location

Pfizer Investigational Site

Barcelona, Barcelona, 08035, Spain

Location

Pfizer Investigational Site

Gothenburg, 413 45, Sweden

Location

Pfizer Investigational Site

Stockholm, 171 76, Sweden

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

2-amino-8-(4-(2-hydroxyethoxy)cyclohexyl)-6-(6-methoxypyridin-3-yl)-4-methylpyrido(2,3-d)pyrimidin-7(8H)-one; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Study was prematurely terminated due to PF-04691502 tolerability findings that prompted Sponsor to re-evaluate strategic goals of program. Unexpected frequency of severe skin toxicity was observed and no participant was enrolled in phase 2 of study.

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 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: September 8, 2011
• Study Start: March 1, 2012
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 12, 2014
• Results First Posted: August 12, 2014

Record last verified: 2014-07

Locations

IT (1); ES (1); SE (2); BE (1)