Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive, HER2 Negative Invasive Breast Cancer

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT02040857
• Collaborator: Pfizer (Industry)
• Enrollment: 162
• Locations: 10
• Arm: 1
• Duration (Months): 76
• Patients Per Site: 16.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This research study is evaluating a drug called Palbociclib in combination with endocrine therapy as a possible treatment for hormone receptor positive breast cancer.

• Palbociclib is a drug that may stop cancer cells from growing. Palbociclib blocks activity of two closely related enzymes (proteins that help chemical reactions in the body occur), called Cyclin D Kinases 4 and 6 (CDK 4/6). These proteins are part of a pathway, or a sequence of steps which is known to regulate cell growth. Laboratory testing has suggested palbociclib may stop the growth of hormone receptor positive breast cancer.

• Endocrine therapy prevents breast cancer cell growth by blocking estrogen stimulation. During this study endocrine therapy will either be tamoxifen or an aromatase inhibitor. It is standard of care for premenopausal women to take tamoxifen and for postmenopausal women to take either an aromatase inhibitor or tamoxifen after a diagnosis of hormone receptor positive breast cancer.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Drug: Palbociclib; Drug: Aromatase Inhibitor	Phase 2

Detailed Description

After the screening procedures confirms that the participant is able to participate in the study. The participant will be given a dosing diary for each treatment cycle. Each treatment cycle lasts 28 days, during which time the participant will take Palbociclib once a day on days 1-21 of each 28 day cycle and the aromatase inhibitor that the participant is already taking once a day every day. The diary will also include special instructions for taking the study drug(s).

All participants participating in the research study will receive the same dose of Palbociclib.

While participating in the research study the participant will have the following tests and procedures:

• Clinical Exams: The participant will have a physical exam on the first day of the month for first three months of therapy. After that, the participant will have a physical exam every other month until the end of the first year of therapy. After the first year, the participant will have a physical exam every 3 months during the second year of therapy. During the physical exam, the participant will be asked questions about their general health, questions about any problems that they may be experiencing, and any medications they are taking.

• Blood tests: The participant will have blood drawn on the first and fifteenth days of the first three months of therapy. After that, the participant will have blood drawn every month for the remainder of the first year of treatment and the every other month until the end of therapy. These tests will be used to determine if the participant is having any side effects related to the study drug.

• Electrocardiograms (EKG): The participant will have an EKG performed on the first day of the first three months of therapy. After that, the participant will have an EKG every other month until the end of the first year of therapy. After the first year of therapy, the participant will have an EKG every 3 months during the second year of therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 162 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Pilot Feasibility Study of Palbociclib in Combination With Adjuvant Endocrine Therapy for Hormone Receptor Positive Invasive Breast Carcinoma
• Study Start Date: Jan 1, 2014
• Actual Primary Completion Date: May 1, 2018
• Actual Study Completion Date: May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Palbociclib With Adjuvant Endocrine Therapy Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd	Drug: Palbociclib; CDK 4/6 inhibitor; Other Names: PD 0332991-0054 PD-0332991 PD-332991 PF-00080665-73 ; Drug: Aromatase Inhibitor; Endocrine Therapy; Other Names: Femara Letrozole Anastrozole Arimidex Exemestane Aromasin Tamoxifen Nolvadex

Outcome Measures

Primary Outcome Measures

1. 2-Year Treatment Discontinuation Rate [Evaluate upon completion of palbociclib, up to 2 years of treatment completion.]

   The 2-year treatment discontinuation rate is the percentage of participants who do not complete the palbociclib treatment per protocol for reasons due to toxicity, withdrawal of consent to be treated, or other events related to tolerability in uncensored participants. Participants who discontinued palbociclib early for reasons that were not treatment-related were censored.

Secondary Outcome Measures

1. 2-year Treatment Discontinuation Rate by Aromatase Inhibitor and Tamoxifen-based Therapy Subgroup [Evaluate upon completion of palbociclib, up to 2 years of treatment completion.]

   The 2-year treatment discontinuation rate is the percentage of participants who do not complete the palbociclib treatment per protocol for reason due to toxicity, withdrawal of consent to be treated, or other events related to tolerability of all enrolled participants.

2. Grade 3-4 Treatment-Related Neutropenia Toxicity Rate [AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.]

   Grade 3-4 treatment-related neutropenia toxicity rate is the percentage of participants experiencing at least one grade 3-4 neutropenia AE with treatment attribution of possible, probable or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) during the time of observation on treatment as reported on case report forms.

3. All Grade Treatment-Related Fatigue Toxicity Rate [AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.]

   All grade treatment-related fatigue toxicity rate is the percentage of participants experiencing at least one grade 1-4 fatigue AE with treatment attribution of possible, probable or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) during the time of observation on treatment as reported on case report forms.

4. All GradeTreatment-Related Alopecia Toxicity Rate [AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.]

   All grade treatment-related alopecia toxicity rate is the percentage of participants experiencing at least one grade 1-4 alopecia AE with treatment attribution of possible, probable or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) during the time of observation on treatment as reported on case report forms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants must have histologically confirmed hormone receptor positive (HR+) HER2 negative stage II (except T2N0) or stage III invasive breast cancer. Evaluation for metastatic disease is not required in the absence of symptoms.

• Men and both pre- and postmenopausal women are eligible.

• Prior Treatment:

• Participants may have received (neo)adjuvant chemotherapy, but must be at least 30 days after last dose, with no more than grade 1 residual toxicity at time of screening.

• Participants may have received adjuvant radiotherapy, but must be at least 30 days after last dose , with no more than grade 1 residual toxicity at the time of screening.

• If most recent therapy was surgery, participants must be at least 30 days out from definitive surgery with no active wound healing complications.

• Participants must have demonstrated ability to tolerate endocrine therapy by prior successful completion of at least 1 month of tamoxifen or aromatase inhibitor (AI) therapy without significant adverse events, and in the opinion of the treating physician any ongoing toxicity does not preclude ability to continue on tamoxifen or AI for at least a projected 2 year continuous duration. Ongoing use of any endocrine therapy, including tamoxifen, letrozole, anastrozole, or exemestane, is allowed. Patients may enroll within 2 years of beginning endocrine therapy, as long as there is a plan for at least 2 more years of adjuvant endocrine therapy.

• ECOG performance status 0-1

• Age ≥18 years.

• Normal organ and marrow function

• Baseline QTc ≤ 480 ms

• The effects of palbociclib on the developing human fetus are unknown. Women who might become pregnant must use adequate contraception

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Concurrent therapy with other investigational agents.

• Prior therapy with any CDK4/6 inhibitor.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib.

• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes are ineligible.

• Current use of drugs that are known to prolong the QT interval

• Subjects with organ allograft requiring immunosuppression.

• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• Pregnant women are excluded from this study. Breastfeeding should be discontinued prior to entry onto the study.

• Individuals with a history of a different malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: ductal carcinoma in situ of the breast, cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin.

• No ongoing combination antiretroviral therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, San Francisco	San Francisco	California	United States	94115
2	Indiana University Health Hospital	Indianapolis	Indiana	United States	46202
3	Massachusetts General Hospital	Boston	Massachusetts	United States	02214
4	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
5	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
6	MGH/North Shore Cancer Center	Danvers	Massachusetts	United States	01923
7	DF/DWCC at Milford Regional Cancer Center	Milford	Massachusetts	United States	01757
8	South Shore Hospital	Weymouth	Massachusetts	United States	02190
9	Dana-Farber/New Hampshire Oncology-Hematology	Londonderry	New Hampshire	United States	03053
10	University of Pennsylvania-Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Pfizer

Investigators

• Principal Investigator: Erica Mayer, MD, MPH, Dana-Farber Cancer Institute

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 16, 2016

More Information

Publications

None provided.

• Responsible Party: Erica Mayer, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT02040857
• Other Study ID Numbers: 13-559
• First Posted: Jan 20, 2014
• Last Update Posted: Mar 22, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Erica Mayer, MD, MPH, Principal Investigator, Dana-Farber Cancer Institute: Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Tamoxifen; Letrozole; Palbociclib; Anastrozole; Exemestane; Aromatase Inhibitors

Study Results

Participant Flow

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib: 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Period Title: Overall Study
STARTED	162
Treatment Discontinuation Evaluable	152
COMPLETED	102
NOT COMPLETED	60

Baseline Characteristics

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Overall Participants	162
Age, Customized (Count of Participants)
Age, <50 years	69 42.6%
Age, >50 years	93 57.4%
Sex: Female, Male (Count of Participants)
Female	157 96.9%
Male	5 3.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 1.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	7 4.3%
White	144 88.9%
More than one race	0 0%
Unknown or Not Reported	8 4.9%
Region of Enrollment (participants) [Number]
United States	162 100%
Type of prior neo/adjuvant chemotherapy (Count of Participants)
None	33 20.4%
Neoadjuvant	60 37%
Adjuvant	63 38.9%
Both	4 2.5%
Unknown	2 1.2%

Outcome Measures

1. Primary Outcome

Title	2-Year Treatment Discontinuation Rate
Description	The 2-year treatment discontinuation rate is the percentage of participants who do not complete the palbociclib treatment per protocol for reasons due to toxicity, withdrawal of consent to be treated, or other events related to tolerability in uncensored participants. Participants who discontinued palbociclib early for reasons that were not treatment-related were censored.
Time Frame	Evaluate upon completion of palbociclib, up to 2 years of treatment completion.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all uncensored participants.

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Measure Participants	152
Number (95% Confidence Interval) [percentage of participants]	31 19.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Palbociclib With Adjuvant Endocrine Therapy
	Comments	Primary objective is treatment discontinuation rate at 2 yr for patients receiving Palbociclib therapy. If the true rate of discontinuation by two years is 48% or higher, treatment duration will be considered not feasible and not worthy of further study. If the rate of discontinuation is 33.3% or less, the 2 yr duration will be deemed feasible and worthy of further study. Using a one-sided alpha = 0.025, there is > 90% power to reject the null hypothesis in favor of feasibility.
	Type of Statistical Test	Other
	Comments	Exact binomial test
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Exact binomial test
	Comments

2. Secondary Outcome

Title	2-year Treatment Discontinuation Rate by Aromatase Inhibitor and Tamoxifen-based Therapy Subgroup
Description	The 2-year treatment discontinuation rate is the percentage of participants who do not complete the palbociclib treatment per protocol for reason due to toxicity, withdrawal of consent to be treated, or other events related to tolerability of all enrolled participants.
Time Frame	Evaluate upon completion of palbociclib, up to 2 years of treatment completion.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all enrolled participants.

Arm/Group Title	Aromatase Inhibitor + Palbociclib	Tamoxifen + Palbociclib
Arm/Group Description	participants who received an Aromatase inhibitor as their endocrine therapy with Palbociclib	participants who received Tamoxifen as their endocrine therapy with Palbociclib
Measure Participants	102	60
Number (95% Confidence Interval) [percentage of participants]	28 17.3%	35 NaN

3. Secondary Outcome

Title	Grade 3-4 Treatment-Related Neutropenia Toxicity Rate
Description	Grade 3-4 treatment-related neutropenia toxicity rate is the percentage of participants experiencing at least one grade 3-4 neutropenia AE with treatment attribution of possible, probable or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) during the time of observation on treatment as reported on case report forms.
Time Frame	AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all enrolled participants.

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Measure Participants	162
Number (95% Confidence Interval) [percentage of participants]	54 33.3%

4. Secondary Outcome

Title	All Grade Treatment-Related Fatigue Toxicity Rate
Description	All grade treatment-related fatigue toxicity rate is the percentage of participants experiencing at least one grade 1-4 fatigue AE with treatment attribution of possible, probable or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) during the time of observation on treatment as reported on case report forms.
Time Frame	AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all enrolled participants.

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Measure Participants	162
Number (95% Confidence Interval) [percentage of participants]	76 46.9%

5. Secondary Outcome

Title	All GradeTreatment-Related Alopecia Toxicity Rate
Description	All grade treatment-related alopecia toxicity rate is the percentage of participants experiencing at least one grade 1-4 alopecia AE with treatment attribution of possible, probable or definite based on NCI Common Toxicity Criteria for Adverse Events version 4 (CTCAEv4) during the time of observation on treatment as reported on case report forms.
Time Frame	AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all enrolled participants.

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib: 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Measure Participants	162
Number (95% Confidence Interval) [percentage of participants]	28 17.3%

6. Post-Hoc Outcome

Title	Rate of Treatment Related Discontinuation
Description	The 2-year treatment discontinuation rate is the percentage of participants who do not complete the palbociclib treatment per protocol for reasons due to toxicity, withdrawal of consent to be treated, or other events related to tolerability in all enrolled participants.
Time Frame	Evaluate upon completion of combination therapy with endocrine therapy plus palbociclib, up to 2 years of treatment completion.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all enrolled participants.

Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
Measure Participants	162
Number (95% Confidence Interval) [percentage of participants]	63 38.9%

Adverse Events

Time Frame	AE data collected every cycle from the time of the first dose of study treatment, through the study and until 30 days after removal from study or death, whichever occurs first. Therefore, AEs were observed up to 2 years plus 30 days.
Adverse Event Reporting Description	Serious AEs (SAE) were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher. All remaining AEs are classified as Other AEs (OAE) including grade 3 or higher events with treatment-attribution of unlikely and unrelated plus all grade 1 and 2 events. Maximum grade toxicity by type was then calculated within SAE and OAE datasets. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	Palbociclib With Adjuvant Endocrine Therapy
Arm/Group Description	Palbociclib 125 mg PO qd 21 days on, 7 days off Endocrine Therapy: Tamoxifen 20mg, Letrozole 2.5mg, Anastrozole 1mg, or Exemestane 25mg PO qd
All Cause Mortality
	Palbociclib With Adjuvant Endocrine Therapy
	Affected / at Risk (%)	# Events
Total	0/162 (0%)
Serious Adverse Events
	Palbociclib With Adjuvant Endocrine Therapy
	Affected / at Risk (%)	# Events
Total	96/162 (59.3%)
Cardiac disorders
Cardiac disorders - Other, specify	2/162 (1.2%)
Gastrointestinal disorders
Diarrhea	1/162 (0.6%)
Mucositis oral	2/162 (1.2%)
Nausea	1/162 (0.6%)
General disorders
Fatigue	6/162 (3.7%)
Infections and infestations
Breast infection	2/162 (1.2%)
Soft tissue infection	1/162 (0.6%)
Investigations
Lymphocyte count decreased	2/162 (1.2%)
Neutrophil count decreased	78/162 (48.1%)
Vascular disorders
Hypertension	1/162 (0.6%)
Other (Not Including Serious) Adverse Events
	Palbociclib With Adjuvant Endocrine Therapy
	Affected / at Risk (%)	# Events
Total	162/162 (100%)
Blood and lymphatic system disorders
Anemia	42/162 (25.9%)
Lymph node pain	2/162 (1.2%)
Blood and lymphatic system disorders - Other, specify	3/162 (1.9%)
Cardiac disorders
Chest pain - cardiac	1/162 (0.6%)
Palpitations	7/162 (4.3%)
Sinus bradycardia	1/162 (0.6%)
Sinus tachycardia	2/162 (1.2%)
Cardiac disorders - Other, specify	2/162 (1.2%)
Ear and labyrinth disorders
Ear pain	2/162 (1.2%)
Tinnitus	4/162 (2.5%)
Vertigo	2/162 (1.2%)
Vestibular disorder	1/162 (0.6%)
Ear and labyrinth disorders - Other, specify	2/162 (1.2%)
Gastrointestinal disorders
Dyspepsia	1/162 (0.6%)
Mucositis oral	1/162 (0.6%)
General disorders
Chills	3/162 (1.9%)
Edema limbs	9/162 (5.6%)
Fatigue	58/162 (35.8%)
Fever	1/162 (0.6%)
Flu like symptoms	1/162 (0.6%)
Localized edema	1/162 (0.6%)
Non-cardiac chest pain	2/162 (1.2%)
Pain	4/162 (2.5%)
Infections and infestations
Bronchial infection	1/162 (0.6%)
Skin infection	1/162 (0.6%)
Investigations
Neutrophil count decreased	4/162 (2.5%)
Skin and subcutaneous tissue disorders
Alopecia	2/162 (1.2%)
Dry skin	1/162 (0.6%)
Pain of skin	1/162 (0.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.