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PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01723774
Recruitment Status : Active, not recruiting
First Posted : November 8, 2012
Last Update Posted : August 3, 2021
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE November 6, 2012
First Posted Date  ICMJE November 8, 2012
Last Update Posted Date August 3, 2021
Actual Study Start Date  ICMJE April 10, 2013
Actual Primary Completion Date April 13, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2016)
  • Complete cell cycle arrest in women without PIK3CA hotspot mutation (PIK3CA Wild Type Cohort) [ Time Frame: 2 weeks (C1D15) ]
    Complete cell cycle arrest is defined as Ki67 ≥ 2.7% following 2 weeks of neoadjuvant PD 0332991
  • Complete cell cycle arrest in women with endocrine resistant cancer [ Time Frame: 2 weeks (C1D15) ]
    Complete cell cycle arrest is defined as Ki67 ≥ 2.7% following 2 weeks of neoadjuvant PD 0332991
Original Primary Outcome Measures  ICMJE
 (submitted: November 6, 2012)
Pathologic complete response (pCR) [ Time Frame: 15 weeks ]
A pathologic complete response (pCR) is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes taken at time of surgery at 15 weeks.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 24, 2016)
  • Rate of PEPI 0 score [ Time Frame: 30 days following the last day of study treatment. ]
  • Radiologic response rate [ Time Frame: 16 weeks ]
    The radiological response rate will be estimated by the number of patients whose disease meets with WHO criteria for complete or partial response at the evaluation prior to surgery divided by the total number of eligible patients who began combination neo-adjuvant therapy.
  • Ki67 level post 2 weeks of PD 332991 [ Time Frame: 2 weeks ]
    Following the approach of Dowsett et al., the percent change in the Ki67 level from baseline will be determined on the log scale. A 95% t-confidence interval for the mean percent change in the Ki67 level from baseline will be constructed (if appropriate). Logistic regression modeling will be used to examine which baseline patient and/or tumor characteristics are associated with the likelihood of a Ki67 being at or below 10%.
  • Concentration of PD 0332991 [ Time Frame: 2 weeks ]
    Blood will be drawn for PKs on Cycle 1 Day 15. At each time point, blood will be drawn prior to drug administration and 90 minutes following drug administration. This will be done in the first 16 patients in the PIK3CA wild type cohort only.
  • Rate of cell cycle arrest [ Time Frame: 2 weeks (cycle 1 day 1 and cycle 1 day 15) ]
    Compare rate of complete cell cycle (defined as Ki67 < 2.7%) arrest between C1D1 and C1D15
  • Ki67 level of tumor specimens [ Time Frame: 5 months ]
    To assess Ki67 level on serially collected tumor specimens (baseline, C1D1, C1D15, and time of surgery)
  • Pathologic complete response (pCR) rate [ Time Frame: 5 months ]
  • Concentration of anastrozole [ Time Frame: 2 weeks ]
    Blood will be drawn for PKs prior to initiation of PD 0332991 but after patients have taken anastrozole alone or in combination with goserelin for at least 2 weeks (this could be done on Cycle 1 Day 1) and again on Cycle 1 Day 15. At each time point, blood will be drawn prior to drug administration and 90 minutes following drug administration. This will be done in the first 16 patients in the PIK3CA wild type cohort only.
  • Safety of PD 0332991 in combination in anastrozole as measured by frequency and grade of adverse events [ Time Frame: 15 weeks ]
    The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Complete cell cycle arrest in women with PIK3CA hotspot mutation [ Time Frame: 2 weeks (C1D15) ]
    Complete cell cycle arrest is defined as Ki67 ≥ 2.7% following 2 weeks of neoadjuvant PD 0332991
  • Safety profile of study therapy during adjuvant therapy as measured by frequency and grade of adverse event [ Time Frame: From start of adjuvant therapy to completion of adjuvant therapy (up to 2 years) ]
    The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Overall survival [ Time Frame: 5 years ]
  • Relapse-free survival [ Time Frame: 5 years ]
  • Clinical response rate [ Time Frame: 16 weeks ]
    The clinical response rate will be estimated by the number of patients whose disease meets the WHO criteria of complete or partial response prior to surgery divided by the total number of eligible patients who began combination neoadjuvant treatment.
  • Local recurrence rate [ Time Frame: 5 years ]
    Local recurrence is defined as histologic evidence of ductal carcinoma in situ or invasive breast cancer in the ipsilateral breast or chest wall.
  • Regional recurrence rate [ Time Frame: 5 years ]
    Regional recurrence is defined as the cytologic or histologic evidence of disease in the ipsilateral internal mammary, ipsilateral supraclavicular, ipsilateral infraclavicular and/or ipsilateral axillary nodes or soft tissue of the ipsilateral axilla.
  • Distant recurrence rate [ Time Frame: 5 years ]
    Distant recurrence is defined as the cytologic, histologic, and/or radiographic evidence of disease in the skin, subcutaneous tissue, lymph nodes (other than local or regional metastasis), lung, bone narrow, central nervous system or histologic and/or radiographic evidence of skeletal or liver metastasis.
  • Rate of second primary breast cancer [ Time Frame: 5 years ]
    Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.
  • Rate of second primary cancer (non-breast) [ Time Frame: 5 years ]
    Second primary cancer (non-breast) is defined as any non-breast second primary cancer other than squamous or basal cell carcinoma of the skin, melanoma in situ, or carcinoma in situ of the cervix is to be reported and should be confirmed histologically whenever possible.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 6, 2012)
  • Safety of PD 0332991 in combination in anastrozole [ Time Frame: 15 weeks ]
    The maximum grade for each type of adverse event will be recorded for each patient using the NCI-CTCAE v4.0 coding scheme, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
  • Clinical response and radiologic response [ Time Frame: 15 weeks ]
    Physical examination: Prior cycle 0 and at the end of each neoadjuvant treatment cycle cycles (that is, at the end of cycles 0-4) the longest axis and the perpendicular axis of the measurable lesion should be measured and recorded in metric notation by tape, ruler or caliper technique on the case report forms. Radiographic evaluation of tumor size: Mammogram and ultrasound imaging will be performed prior to cycle 0 and at the end of cycle 4 combination therapy for bidimensional measurement of the tumor. WHO criteria will be used to assess clinical response:
  • Ki67 level post 2 weeks of PD 332991 [ Time Frame: 2 weeks ]
    Following the approach of Dowsett et al., the percent change in the Ki67 level from baseline will be determined on the log scale. A 95% t-confidence interval for the mean percent change in the Ki67 level from baseline will be constructed (if appropriate). Logistic regression modeling will be used to examine which baseline patient and/or tumor characteristics are associated with the likelihood of a Ki67 being at or below 10%.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer
Official Title  ICMJE A Phase II Trial of Neoadjuvant PD 0332991, a Cyclin-Dependent Kinase (Cdk) 4/6 Inhibitor, in Combination With Anastrozole in Women With Clinical Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer
Brief Summary A Phase II study to investigate the potential utility of PD 0332991 in the treatment of early stage ER+ Human epidermal growth factor receptor 2 (HER2)- breast cancer, to investigate whether the combination of PD 0332991 and anastrozole is able to: 1) improve the pathologic complete response rate when compared to the historical control of single agent aromatase inhibitors, 2) result in fewer patients with on therapy Ki67>10% compared to historical control.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Neoplasms
Intervention  ICMJE
  • Drug: PD0332991
  • Drug: Anastrozole
    Other Name: Arimidex®
  • Drug: Goserelin
    Other Names:
    • Zoladex®
    • Decapeptide I
  • Procedure: Surgery (standard of care)
    -Breast and axillary lymph node surgery
  • Procedure: Tumor biopsy
Study Arms  ICMJE
  • Experimental: Arm 1: PIK3CA Wild Type Cohort
    • Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
    • Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
    • Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
    • Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
    • Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
    Interventions:
    • Drug: PD0332991
    • Drug: Anastrozole
    • Drug: Goserelin
    • Procedure: Surgery (standard of care)
    • Procedure: Tumor biopsy
  • Experimental: Arm 2: PIK3CA Mutant Type Cohort
    • Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
    • Cycle 0 is 28 days of anastrozole PO daily and, if premenopausal, goserelin SC every 28 days.
    • Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
    • Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
    • Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
    Interventions:
    • Drug: PD0332991
    • Drug: Anastrozole
    • Drug: Goserelin
    • Procedure: Surgery (standard of care)
    • Procedure: Tumor biopsy
  • Experimental: Arm 3: Endocrine Resistant Cohort
    • Tumor biopsy for testing/research at baseline and Cycle 1 Day 15
    • Cycles 1-5: PD 0332991 combined with anastrozole (and goserelin if premenopausal) is to be (4) 28-day cycles followed by a 5th cycle of 10-12 days duration consisting of daily PD 0332991 and anastrozole (last dose day before surgery)
    • Standard surgery will be performed per institutional standards 2-4 weeks following the completion of Cycle 4 in those who did not receive Cycle 5. In patients who receive Cycle 5, surgery occurs on Day 11, 12, or 13 of Cycle 5.
    • Patients who derived benefit from the therapy have the option of taking PD 0332991 in combination with endocrine therapy for 23 cycles after surgery and adjuvant chemotherapy and radiation if indicated. It should be re-started at least 4 weeks after the completion of chemotherapy and radiation therapy if these treatments were planned.
    Interventions:
    • Drug: PD0332991
    • Drug: Anastrozole
    • Drug: Goserelin
    • Procedure: Surgery (standard of care)
    • Procedure: Tumor biopsy
Publications * Bagegni N, Thomas S, Liu N, Luo J, Hoog J, Northfelt DW, Goetz MP, Forero A, Bergqvist M, Karen J, Neumüller M, Suh EM, Guo Z, Vij K, Sanati S, Ellis M, Ma CX. Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early-stage breast cancer receiving neoadjuvant palbociclib. Breast Cancer Res. 2017 Nov 21;19(1):123. doi: 10.1186/s13058-017-0913-7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 31, 2021)
84
Original Estimated Enrollment  ICMJE
 (submitted: November 6, 2012)
29
Estimated Study Completion Date  ICMJE April 30, 2027
Actual Primary Completion Date April 13, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Pre-registration PIK3CA Mutant Inclusion

  • Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible
  • Female ≥18 years of age
  • ECOG performance status of 0, 1 or 2
  • Life expectancy > 4 months
  • Premenopausal, patient must be willing to comply with pregnancy requirements
  • Adequate organ and marrow function

    • leukocytes ≥ 3,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 100,000/mcL
    • total bilirubin ≤ ULN
    • AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
    • Creatinine ≤ ULN
  • Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

  • Prior treatment of this cancer including: surgery, radiation, chemotherapy, biotherapy, hormonal therapy, investigational agent prior to study entry
  • Receiving any investigational agents
  • Prior therapy with any Cdk4 inhibitor
  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant/nursing
  • Unwilling to employ adequate contraception
  • Known HIV-positive on combination antiretroviral therapy
  • Evidence of inflammatory cancer
  • Known metastatic disease
  • Current use of anticoagulation therapy
  • Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
  • Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
  • Corrected QT interval >470 msec

Registration PIK3CA Mutant Inclusion The criteria below must be met in addition to the pre-registration criteria, except treatment with endocrine therapy for this cancer is allowed prior to registration

  • PIK3CA mutant cohort: tumor PIK3CA mutation present
  • Premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration

Exclusion Criteria below must be met in addition to the pre-registration criteria -Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

PIK3CA Wild Type Inclusion

  • Clinical T2-T4c, any N, M0 invasive ER+ (Allred Score of 6-8) and HER2 negative (0 or 1+ by IHC or FISH negative for amplification) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive ER+ (Allred Score of 6-8) HER2- breast cancer or DCIS in the contralateral breast the patient are eligible
  • For the PIK3CA wild type cohort: tumor PIK3CA mutation absent. Note that if a patient did not have sufficient research tissue for PIK3CA sequencing at pre-registration or if PIK3CA sequencing result is delayed, she could be registered and enrolled on the PD991 trial without assigning to a particular cohort at the time of enrollment. PIK3CA sequencing will be performed in the future on tumors collected at subsequent time points to assign the treatment cohort or when the PIK3CA sequencing data is available
  • For the endocrine resistant cohort: Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. Note that prior neoadjuvant endocrine therapy could include any endocrine therapy (including aromatase inhibitor, tamoxifen, fulvestrant) alone or in combination, or endocrine therapy in combination with any investigational agent that is not a Cdk 4/6 inhibitor

    *Patients who had a Day 17 Ki67 > 10% from the NCI9170 trial are eligible for the endocrine resistant cohort

  • Female >18 years of age
  • ECOG performance status of 0, 1 or 2
  • Life expectancy > 4 months
  • If premenopausal, patient must be willing to comply with pregnancy requirements
  • Adequate organ and marrow function:

    • leukocytes ≥ 3,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 100,000/mcL
    • total bilirubin ≤ ULN
    • AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
    • Creatinine ≤ ULN
  • In premenopausal women, serum estradiol level in postmenopausal range ≤ 7 days prior to registration.
  • Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

  • Prior treatment of this cancer including: Surgery, Radiation therapy, Chemotherapy, Biotherapy, Hormonal therapy, Investigational agent prior to study entry
  • Receiving any other investigational agents
  • Prior therapy with any Cdk4 inhibitor
  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant/nursing
  • Unwilling to employ adequate contraception
  • Known HIV-positive on combination antiretroviral therapy
  • Evidence of inflammatory cancer
  • Known metastatic disease
  • Current use of anticoagulation therapy
  • Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
  • Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
  • Corrected QT interval >470 msec
  • Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

Endocrine Resistant Inclusion

  • Clinical T2-T4c at diagnosis or screening, any N, M0 invasive ER+ (Allred Score at least 3 or > 1% ER positivity) and HER2 negative (0 or 1+ by IHC or FISH negative or equivocal) breast cancer, by AJCC 7th edition clinical staging, with the goal being surgery to completely excise the tumor in the breast and the lymph node. Note: Patients with invasive breast cancer that is ER pos, HER2 neg or equivocal or DCIS in the contralateral breast are eligible; multi-focal diseases are not excluded. The dominant lesion will be followed per protocol
  • Ki67 > 10% by central testing at Washington University AMP laboratory from a tumor biopsy performed after at least 2 weeks on neoadjuvant endocrine therapy. If Ki67 is > 10% by local testing, the Ki67 slide and H&E slide need to be reviewed by the study pathologist to confirm eligibility (discuss with Study Chair). For patients external to Washington University, please contact the Washington University coordinator by email so that a screening ID# can be assigned prior to shipment of the slides
  • Female ≥ 18 years of age
  • ECOG performance status of 0, 1 or 2
  • Pre- or post-menopausal women are eligible. If premenopausal, patient must be willing to comply with pregnancy requirements and agrees with GnRH agonist therapy for ovarian suppression during the study
  • Adequate organ and marrow function:

    • Leukocytes ≥ 3,000/mcL
    • Absolute neutrophil count ≥ 1,500/mcL
    • Platelets ≥ 100,000/mcL
    • Total bilirubin ≤ ULN
    • AST(SGOT)/ and ALT(SGPT) < 2.5 X ULN
    • Creatinine ≤ ULN
  • Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

  • Prior treatment of this cancer including: Surgery, Radiation, Chemotherapy
  • Receiving any other investigational agents
  • Prior therapy with Cdk4 inhibitor
  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant/nursing
  • Unwilling to employ adequate contraception
  • Known HIV-positive on combination antiretroviral therapy
  • Known metastatic disease
  • Current use of anticoagulation therapy
  • Previous excisional biopsy of the breast cancer or sentinel lymph node biopsy
  • Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
  • Corrected QT interval >470 msec
  • Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)

Adjuvant Inclusion

  • Derived benefit from PD 0332991 in the neoadjuvant setting in this trial. This includes the 26 patients who achieved complete cell cycle arrest only after the addition of PD 0332991 (C1D1 Ki67 >2.7% and C1D15 Ki67 ≤ 2.7%) from the main study (PIK3CA WT, mutant, or unknown cohorts) as well as any patients who have a Ki67 ≤ 10% on C1D15 biopsy in the endocrine resistant cohort
  • ECOG performance status of 0, 1 or 2
  • Premenopausal, patient must be willing to comply with pregnancy requirements laid out
  • Adequate organ and marrow function

    • leukocytes ≥ 3,000/mcL
    • absolute neutrophil count ≥ 1,500/mcL
    • platelets ≥ 100,000/mcL
    • total bilirubin ≤ ULN
    • AST(SGOT)/ and ALT(SGPT) ≤ 2.5 X ULN
    • Creatinine ≤ ULN
  • Underwent surgery of the breast and axilla for curative intent
  • At least 4 weeks post completion of adjuvant chemotherapy and radiation therapy if indicated
  • Patients who already started on adjuvant hormonal therapy are eligible under the following conditions:

    • For the 26 patients who enrolled in the initial cohorts and derived benefit from neoadjuvant PD 0332991 (C1D1 Ki67 >2.7% and C1D15 Ki67 ≤ 2.7%), adjuvant PD 0332991 should be initiated as soon as possible if adjuvant hormonal therapy has been initiated and the patient has completed radiation if indicated
    • For patients who enrolled in the endocrine resistant cohort and derived benefit from neoadjuvant PD 0332991 (C1D15 Ki67 ≤ 10%), adjuvant PD 0332991 should be initiated within 6 months or sooner after initation of adjuvant hormonal therapy
  • Able to understand and willing to sign an IRB-approved written informed consent document

Exclusion

  • Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism
  • Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled symptomatic cardiac arrhythmia, ssychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant/nursing
  • Unwilling to employ adequate contraception
  • Known HIV-positive on combination antiretroviral therapy. -Known metastatic disease
  • Any condition that impairs patient's ability to swallow PD 0332991 tablets (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, prior surgical procedures affecting absorption)
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PD 0332991 or other agents used in the study
  • Corrected QT interval >470 msec
  • Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John's wort)
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01723774
Other Study ID Numbers  ICMJE 201301106
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator: Cynthia Ma, M.D., Ph.D. Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP