Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Antineoplastic Agents

Estrogens

Palbociclib

Goserelin

Anastrozole

Antineoplastic Agents, Hormonal

Aromatase Inhibitors

Enzyme Inhibitors

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Protein Kinase Inhibitors

* 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.

* 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.

PD0332991

Surgery (standard of care)

Tumor biopsy

Cynthia X Ma, M.D., Ph.D.

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.

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

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

Complete cell cycle arrest is defined as Ki67 ≤ 2.7% following 2 weeks of neoadjuvant PD 0332991

Compare rate of complete cell cycle arrest (defined as Ki67 ≤ 2.7%) arrest between C1D1 and C1D15

* 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.

* 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.

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.

* 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.

To assess Ki67 level on serially collected tumor specimens

-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.

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 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 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.

Second primary breast cancer is defined histologic evidence of ductal carcinoma in situ or invasive breast cancer in the contralateral breast or chest wall.

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.

Pfizer

Washington University School of Medicine

Arm 1: PIK3CA Wild Type Cohort

Arm 2: PIK3CA Mutant Type Cohort

Arm 3: Endocrine Resistant Cohort

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.

Adjuvant Continuation

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Cynthia X. Ma, M.D., Ph.D.

Arm 2 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 1: PIK3CA Wild Type Cohort only. 5 participants in Arm 1 were not evaluable. 1 participant was not evaluable due to insufficient quality of specimen, 1 participant was not evaluable because she withdrew prior to starting treatment, 2 participants were not evaluable because there was no tumor present on biopsy, and 1 participant was not evaluable because she withdrew prior to cycle 1 day 15 biopsy.

Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (PIK3CA Wild Type Cohort Only)

Arm 1 and Arm 2 participants were not evaluable for this outcome measure as it is for Arm 3: Endocrine Resistant Cohort only. 1 participant was not evaluable for this outcome measure as the participant did not have any tissue available at the cycle 1 day 15 biopsy.

Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 (Endocrine Resistant Cohort Only)

Arm 1 and Arm 3 participants were not evaluable for this outcome measure as it is for Arm 2: PIK3CA Mutant Type Cohort only.

Number of Participants With Complete Cell Cycle Arrest at Cycle 1 Day 15 ( PIK3CA Mutant Type Cohort Only)

Cycle 1 Day 1 complete cell cycle arrest

Cycle 1 Day 15 complete cell cycle arrest

PIK3CA Wild Type Cohort - 5 participants not evaluable. 1 due to insufficient quality of specimen, 1 because she withdrew prior to starting treatment, 2 participants because there was no tumor present on biopsy, and 1 because she withdrew prior to cycle 1 day 15 biopsy. Endocrine Resistant Cohort-1 participant because no tissue available at the cycle 1 day 15 biopsy.

Number of Participants With Complete Cell Cycle Arrest

7 participants in Arm 1 were not evaluable for this outcome measure. 3 participants in Arm 2 were not evaluable for this outcome measure. 12 participants in Arm 3 were not evaluable for this outcome measure. Reasons include patient withdrawal (n=4), progressive disease during cycle 1 (n=2), cycle 1 day 15 Ki67 \>10% (n=14) high estradiol (n=1), and adverse event (n=1).

Clinical Response Rate

Arm 1 PIK3CA Wild Type Cohort: 23 participants not evaluable due to imaging not being performed. Arm 2 PIK3CA Mutant Type Cohort: 9 participants not evaluable due to imaging not being performed. Arm 3 Endocrine Resistant Cohort: 10 participants not evaluable due to imaging not being performed.

Radiologic Response Rate

Grade 1/2 anemia

Grade 1/2 dry eye

Grade 1/2 constipation

Grade 1/2 diarrhea

Grade 1/2 dry mouth

Grade 1/2 dyspepsia

Grade 1/2 flatulence

Grade 1/2 gastroesophageal reflux disease

Grade 1/2 gastrointestinal pain

Grade 1/2 mucositis oral

Grade 1/2 nausea

Grade 1/2 oral pain

Grade 1/2 rectal pain

Grade 1/2 stomatitis

Grade 1/2 vomiting

Grade 1/2 chills

Grade 1/2 edema limbs

Grade 1/2 fatigue

Grade 1/2 fever

Grade 1/2 localized edema

Grade 1/2 pain

Grade 1/2 shingles

Grade 1/2 sinusitis

Grade 1/2 urinary tract infection

Grade 1/2 seroma

Grade 1/2 alanine aminotransferase increased

Grade 3/4 alanine aminotransferase increased

Grade 1/2 aspartate aminotransferase increased

Grade 3/4 aspartate aminotransferase increased

Grade 1/2 lymphocyte count decreased

Grade 1/2 neutrophil count decreased

Grade 3/4 neutrophil count decreased

Grade 1/2 platelet count decreased

Grade 1/2 weight loss

Grade 1/2 white blood cell decreased

Grade 3/4 white blood cell decreased

Grade 1/2 anorexia

Grade 1/2 hypocalcemia

Grade 1/2 hypokalemia

Grade 1/2 hyponatremia

Grade 1/2 arthralgia

Grade 1/2 back pain

Grade 1/2 bone pain

Grade 1/2 myalgia

Grade 1/2 osteoporosis

Grade 1/2 dizziness

Grade 1/2 dysgeusia

Grade 1/2 headache

Grade 1/2 memory impairment

Grade 1/2 peripheral motor neuropathy

Grade 1/2 peripheral sensory neuropathy

Grade 1/2 confusion

Grade 1/2 depression

Grade 1/2 insomnia

Grade 1/2 pelvic pain

Grade 1/2 allergic rhinitis

Grade 1/2 cough

Grade 1/2 dyspnea

Grade 1/2 epistaxis

Grade 1/2 nasal congestion

Grade 1/2 postnasal drip

Grade 1/2 sore throat

Grade 1/2 alopecia

Grade 1/2 dry skin

Grade 1/2 hyperhidrosis

Grade 1/2 papulopustular rash

Grade 1/2 pruritus

Grade 1/2 rash maculo-papular

Grade 3/4 rash maculo-papular

Grade 1/2 fever blister

Grade 1/2 itching

Grade 1/2 hot flashes

Safety of PD 0332991 in Combination in Anastrozole as Measured by Frequency and Grade of Related Adverse Events

Some participants were not evaluable for this outcome measure due to participant withdrawal and surgery not completed.

Number of Participants With a PEPI-0 Score

Pre-treatment

Cycle 1 Day 15

Only participants who had tissue available at the two time points were evaluable for this outcome measure.

Change in Ki67 Level of Tumor Specimens

At time of surgery

Number of Participants With Pathologic Complete Response (pCR)

Grade 1/2 blurred vision

Grade 1/2 watering eyes

Grade 1/2 gastritis

Grade 1/2 upper respiratory infection

Grade 1/2 bruising

Grade 3/4 lymphocyte count decreased

Grade 1/2 white blood cell count decreased

Grade 3/4 white blood cell count decreased

Grade 1/2 hyperglycemia

Safety Profile of Study Therapy During Adjuvant Therapy as Measured by Frequency and Grade of Adverse Event

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer	NCT01723774	Breast Neoplasm...	PD0332991 Anastrozole Goserelin Surgery (standa... Tumor biopsy	18 Years -	Washington University School of Medicine
PD 0332991 and Anastrozole for Stage 2 or 3 Estrogen Receptor Positive and HER2 Negative Breast Cancer	NCT01723774	Breast Neoplasm...	PD0332991 Anastrozole Goserelin Surgery (standa... Tumor biopsy	18 Years -	Washington University School of Medicine

Spots Global Cancer Trial Database for surgery (standard of care)