PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer
- Conditions
- Breast Neoplasms
- Interventions
- Procedure: Surgery (standard of care)Procedure: Tumor biopsy
- Registration Number
- NCT01723774
- Lead Sponsor
- Washington University School of Medicine
- 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: PIK3CA Wild Type Cohort Surgery (standard of care) * 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. Arm 1: PIK3CA Wild Type Cohort Tumor biopsy * 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. Arm 2: PIK3CA Mutant Type Cohort Surgery (standard of care) * 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. Arm 2: PIK3CA Mutant Type Cohort Tumor biopsy * 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. Arm 3: Endocrine Resistant Cohort Surgery (standard of care) * 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. Arm 3: Endocrine Resistant Cohort Tumor biopsy * 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. Arm 3: Endocrine Resistant Cohort PD0332991 * 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. Arm 1: PIK3CA Wild Type Cohort PD0332991 * 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. Arm 2: PIK3CA Mutant Type Cohort PD0332991 * 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. Arm 1: PIK3CA Wild Type Cohort Goserelin * 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. Arm 1: PIK3CA Wild Type Cohort Anastrozole * 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. Arm 2: PIK3CA Mutant Type Cohort Goserelin * 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. Arm 2: PIK3CA Mutant Type Cohort Anastrozole * 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. Arm 3: Endocrine Resistant Cohort Goserelin * 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. Arm 3: Endocrine Resistant Cohort Anastrozole * 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only) At cycle 1 day 15 (2 weeks) Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only) At cycle 1 day 15 (2 weeks) Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
- Secondary Outcome Measures
Name Time Method Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only) At cycle 1 day 15 (2 weeks) Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991
Number of Participants With Complete Cell Cycle Arrest Cycle 1 day 1 and cycle 1 day 15 (2 weeks) Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15
Clinical Response Rate 16 weeks * The clinical response rate is 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.
* Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.
* Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.Radiologic Response Rate At the end of cycle 4 prior to surgery (estimated to be 16 weeks) * The radiological response rate is 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.
* Complete Response (CR) is defined as the disappearance of all known disease based on a comparison between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there is no appearance of new lesions.
* Partial Response (PR) is defined as a 50% or greater decrease in the product of the bidimensional measurements of the lesion (total tumor size) between the pre-treatment measurements and the measurements taken at the completion of neo-adjuvant therapy (that is, at the end of cycle 4 neo-adjuvant combination therapy). In addition there can be no appearance of new lesions or progression of any lesion.Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events From start of treatment through 30 days after completion of an estimated 4 months of neoadjuvant therapy 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 (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.
Number of Participants With a PEPI-0 Score At the time of surgery (estimated to be 5 months) * Preoperative endocrine prognostic index (PEPI) score is derived from four factors assigned a numerical score following neoadjuvant endocrine therapy, including Ki67 expression in the surgical specimen, pathologic tumor size (indicated as "T" below), lymph node status (indicated as "N" below), and estrogen receptor (ER) level (indicated as ER Allred below).
* PEPI-0 score indicates T1 or T2, N0, Ki67 \< 2.7%, ER Allred \> 2.
* It predicts a low risk of recurrence.Change in Ki67 Level of Tumor Specimens Cycle 1 day 15 and at time of surgery (approximately 2-4 weeks post completion of cycle 4 - each cycle is 28 days) To assess Ki67 level on serially collected tumor specimens
Number of Participants With Pathologic Complete Response (pCR) At the time of surgery (estimated to be 5 months) -A pathologic complete response is defined as no histology evidence of invasive tumor cells in the surgical breast specimen and sentinel or axillary lymph nodes.
Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event From start of adjuvant therapy through 30 days after completion of adjuvant therapy (estimated to be 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 (possibly related, probably related, and definitely related) of the adverse event(s) to the study treatment will be taken into consideration.
Overall Survival 5 years Relapse-free Survival 5 years Local Recurrence Rate 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 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 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 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) 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.
Trial Locations
- Locations (4)
Mayo Clinic - Scottsdale
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
University of Alabama
🇺🇸Birmingham, Alabama, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States