Palbociclib After CDK and Endocrine Therapy (PACE)

NCT03147287 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 17-101
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 22

Brief Summary

This research study is studying three combinations of drugs as treatments for breast cancer. The drugs involved in this study are:

• Fulvestrant
• Fulvestrant with Palbociclib
• Fulvestrant with Palbociclib and Avelumab

Conditions

Metastatic Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS), According to RECIST v1.1 Criteria (Investigator Assessment)

  Progression-Free Survival (PFS), according to RECIST v1.1 criteria (investigator assessment): the time from randomization to the earlier of progression or death due to any cause. Participants alive without disease progression were censored at date of last disease assessment (tumor assessments). The date of progression was the first date that recurrent or progressive disease was objectively documented; if death was the defining event, it must have happened within 2 intervals of the last disease assessment, otherwise PFS was censored at last disease assessment. The length of PFS was calculated as PFS time (months) =\[progression/death date(censor date) - randomization date + 1\]/30.4375.

  Tumor were assessed every 8 weeks until 24 weeks, then every 12 weeks. The median PFS follow-up time at database lock was 12.1 months (range 1 day to 50.1 months).

Secondary Outcomes (2)

• Overall Response Rate, According to RECIST v1.1 Criteria (Investigator Assessment)

  Tumor were assessed every 8 weeks until 24 weeks, then every 12 weeks. The median follow-up time for overall response rate at database lock was 12.1 months (range 1 day to 50.1 months).

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability)

  The median follow-up time for adverse event was 5.4 months (range 1.6 months to 51.2 months).

Study Arms (3)

Fulvestrant

ACTIVE COMPARATOR

-Fulvestrant will be administered in the clinic as two IM injections on Cycle 1 Days 1, 15, then monthly

Drug: Fulvestrant

Fulvestrant with Palbociclib

EXPERIMENTAL

* Palbociclib should be taken orally, once per day for 21 days on a 28 days cyclye * Fulvestrant will be administered in the clinic as two IM injections on Cycle 1 Days 1, 15, then monthly

Drug: Palbociclib; Drug: Fulvestrant

Fulvestrant with Palbociclib and Avelumab

EXPERIMENTAL

* Palbociclib should be taken orally, once per day for 21 days on a 28 days cyclye * Fulvestrant will be administered in the clinic as two IM injections on Cycle 1 Days 1, 15, then monthly * Avelumab will be administered intravebously once every 2 weeks

Drug: Palbociclib; Drug: Fulvestrant; Drug: Avelumab

Interventions

Palbociclib DRUG

Palbociclib is a drug that may stop cancer cells from growing

Also known as: Ibrance

Fulvestrant with Palbociclib; Fulvestrant with Palbociclib and Avelumab

Fulvestrant DRUG

Fulvestrant prevents growth of hormone receptor positive breast cancer by blocking stimulation of cancer cells by estrogen

Also known as: Faslodex

Fulvestrant; Fulvestrant with Palbociclib; Fulvestrant with Palbociclib and Avelumab

Avelumab DRUG

Avelumab is an antibody designed to block the PD-1 pathway and helps the immune system in detecting and fighting cancer cells

Also known as: Bavencio

Fulvestrant with Palbociclib and Avelumab

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed hormone receptor positive (HR+) HER2 negative metastatic or locally recurrent unresectable invasive breast cancer. ER, PR and HER2 measurements should be performed according to institutional guidelines, in a CLIA-approved setting. Cut-off values for positive/negative staining should be in accordance with current ASCO/CAP (American Society of Clinical Oncology/College of American Pathologists) guidelines.
• Men and pre- and postmenopausal women are eligible. Ongoing monthly GNRH agonist is required in pre-menopausal women or male participants for at least 4 weeks prior to study entry.
• Participants must have radiological or objective evidence of progression on an endocrine and CDK 4/6 inhibitor regimen in the metastatic setting, and/or relapse/progression during or within 12 months of completion of an endocrine and CDK4/6 inhibitor regimen in the adjuvant setting.
• Participants must have previously been exposed to CDK4/6 inhibitor therapy in combination with endocrine therapy. Exposure to any prior CDK4/6 inhibitor, (including palbociclib, abemaciclib, and ribociclib) is allowed. Patients may have a line of endocrine therapy after combination endocrine and CDK4/6 inhibitor exposure.
• Participants must have remained on prior endocrine and CDK4/6 therapy in the metastatic setting without progression for at least 6 months prior to study entry.
• It is not mandatory to have a CDK 4/6 inhibitor containing regimen as the most recent treatment.
• Participants may have 0-1 prior lines of cytotoxic chemotherapy in the metastatic setting.
• Prior endocrine therapy in the metastatic setting may include any aromatase inhibitor (AI) or tamoxifen, but may not include prior fulvestrant. In the metastatic setting, 1-2 prior lines of endocrine therapy are allowed.
• Participants may have received radiotherapy for palliative purpose, but must not be experiencing \> grade 1 treatment related toxicities, and must have completed treatment \> 14 days prior to registration.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of study agents in participants \<18 years of age, children are excluded from this study.
• ECOG performance status 0-1 (see Appendix A).
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count \> 1,500/µL
• Platelets \> 100,000/µL
• Hemoglobin \> 9g/dL

You may not qualify if:

• Participants who have had endocrine, chemotherapy, and/or biologic therapy within 14 days prior to entering the study or those who have not recovered from any prior treatment-related toxicities (must recover to no more than grade 1. Alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 toxicity not constituting a safety risk based on investigator's judgment are acceptable).
• Participants who are receiving concurrent therapy with other investigational agents.
• Rapidly progressive, symptomatic, visceral spread of disease placing participant at risk of life-threatening complications in the short term.
• Participants with active brain metastases. Stable treated brain metastases are allowed (this includes participants who have documented radiologic stability at least 4 weeks after radiotherapy, and do not require systemic steroids for management of symptoms from CNS metastatic lesions).
• Participants who have discontinued prior palbociclib for toxicity, or have needed more than one dose or schedule reduction for toxicity from prior palbociclib therapy. If a participant required a single dose reduction during prior palbociclib therapy and tolerated it well, for example prior dosing at 100 mg qd 3 weeks on 1 week off schedule, than that dose may be selected for this trial.
• History of allergic reactions to palbociclib or attributed to compounds of similar chemical or biologic composition to palbociclib.
• Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v4.03 Grade ≥ 3)
• Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A isoenzymes are ineligible. Lists including medications and substances known or with the potential to interact with the CYP3A isoenzymes are provided in Appendix B, and can also be found within Section 5.4. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• Current use of drugs listed in Appendix C that are known to prolong the QT interval (See Appendix C)
• Prior organ transplantation including allogenic stem-cell transplantation
• Current use of immunosuppressive medication, except for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection requiring systemic therapy, clinically significant cardiovascular disease including: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication, uncontrolled diabetes mellitus, or psychiatric illness/social situations that would limit compliance with study requirements. Ability to comply with study requirements is to be assessed by each investigator at the time of screening for study participation.
• Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Participants with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment are eligible.
• Known history of testing positive for HIV or known acquired immunodeficiency syndrome, or need to receive combination antiretroviral therapy for HIV
• Known history of immune-mediated conditions including colitis, inflammatory bowel disease requiring steroid or immunosuppressive therapy, pneumonitis, or pulmonary fibrosis.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Pfizer: collaborator

Study Sites (22)

University of Miami

Miami, Florida, 33136, United States

Location

Emory University - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

The University of Kansas Cancer Center - North

Kansas City, Kansas, 64154, United States

Location

The University of Kansas Cancer Center - Overland Park

Overland Park, Kansas, 66210, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

Eastern Maine Medical Center

Bangor, Maine, 04401, United States

Location

Boston Medical Center

Boston, Massachusetts, 02188, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Dana-Farber at St. Elizabeth's Medical Center

Brighton, Massachusetts, 02135, United States

Location

DF/BWCC at Milford Regional Medical Center

Milford, Massachusetts, 01757, United States

Location

DF/BWCC in clinical affiliation with South Shore Hospital

South Weymouth, Massachusetts, 02190, United States

Location

The University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, 64064, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Dana-Farber/New Hampshire Oncology-Hematology

Londonderry, New Hampshire, 03053, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Baylor University

Houston, Texas, 77030, United States

Location

Aurora Cancer Care

Milwaukee, Wisconsin, 53215, United States

Location

Related Publications (1)

• Mayer EL, Ren Y, Wagle N, Mahtani R, Ma C, DeMichele A, Cristofanilli M, Meisel J, Miller KD, Abdou Y, Riley EC, Qamar R, Sharma P, Reid S, Sinclair N, Faggen M, Block CC, Ko N, Partridge AH, Chen WY, DeMeo M, Attaya V, Okpoebo A, Alberti J, Liu Y, Gauthier E, Burstein HJ, Regan MM, Tolaney SM. PACE: A Randomized Phase II Study of Fulvestrant, Palbociclib, and Avelumab After Progression on Cyclin-Dependent Kinase 4/6 Inhibitor and Aromatase Inhibitor for Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor-Negative Metastatic Breast Cancer. J Clin Oncol. 2024 Jun 10;42(17):2050-2060. doi: 10.1200/JCO.23.01940. Epub 2024 Mar 21.

  PMID: 38513188 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Fulvestrant; avelumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Project Manager
• Organization: Dana-Farber Cancer Institute

ctopm@dfci.harvard.edu

617-632-3800

Study Officials

• Erica L Mayer, MD MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Physician, Susan F Smith Center for Women's Cancers

Study Record Dates

• First Submitted: May 5, 2017
• First Posted: May 10, 2017
• Study Start: September 5, 2017
• Primary Completion: December 31, 2022
• Study Completion (Estimated): December 30, 2026
• Last Updated: September 11, 2026
• Results First Posted: December 12, 2023

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (22)