A Study of Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Metastatic Breast Cancer

NCT02384239 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 147522NCI-2015-01791
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 9

Brief Summary

This phase II trial studies the side effects of palbociclib when given together with fulvestrant or tamoxifen citrate in treating patients with hormone receptor positive breast cancer that has spread from where it started to nearby tissue or lymph nodes (locally advanced) or has spread to other places in the body (metastatic). Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Hormone therapy using fulvestrant or tamoxifen citrate may fight breast cancer by blocking the use of estrogen by the tumor cells. Giving palbociclib together with fulvestrant or tamoxifen citrate may work better in treating hormone receptor positive breast cancer.

Conditions

Metastatic Breast Cancer; Hormone Receptor Positive

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Grade 3 or 4 Neutropenia

  Grade 3/4 neutropenia as defined by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.03 in patients with prior exposure to 1-3 lines of chemotherapy for metastatic breast cancer

  Up to 24 months

Secondary Outcomes (6)

• Progression-free Survival (PFS)

  Up to 24 months

• Proportion of Participants With Demonstrated Clinical Benefit

  24 weeks

• Proportion of Participants With an Objective Response

  24 weeks

• Median Change in Percent Positive Cells From Baseline of Ki-67

  Up to 24 months

• Median Change in Percent Positive Cells From Baseline of Total-Rb

  Up to 24 months

Study Arms (2)

Palbociclib 100mg and, fulvestrant or tamoxifen

EXPERIMENTAL

Palbociclib dose 100mg, and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)

Drug: Palbociclib; Drug: Tamoxifen; Drug: Fulvestrant

Palbociclib 125mg and, fulvestrant or tamoxifen

EXPERIMENTAL

Palbociclib dose 125mg and either fulvestrant (500 mg IM on days 1 and 15 in the first 28 days, then every 28 days thereafter) or tamoxifen (20 mg PO daily by physician choice)

Drug: Palbociclib; Drug: Tamoxifen; Drug: Fulvestrant

Interventions

Palbociclib DRUG

Given orally (PO)

Also known as: Ibrance

Palbociclib 100mg and, fulvestrant or tamoxifen; Palbociclib 125mg and, fulvestrant or tamoxifen

Tamoxifen DRUG

Given orally (PO)

Also known as: Tamoxifen 20mg

Palbociclib 100mg and, fulvestrant or tamoxifen; Palbociclib 125mg and, fulvestrant or tamoxifen

Fulvestrant DRUG

Given by intramuscular (IM) injection.

Also known as: Faslodex

Palbociclib 100mg and, fulvestrant or tamoxifen; Palbociclib 125mg and, fulvestrant or tamoxifen

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically proven diagnosis of breast cancer with evidence of metastatic or locally advanced disease, not amenable to resection or radiation therapy with curative intent.
• Patients 18 years of age or older, Female patients should be either:
• Postmenopausal, as defined by at least one of the following criteria:
• Age \>=60 years;
• Age \<60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause;
• Documented bilateral oophorectomy;
• Medically confirmed ovarian failure.
• Pre/peri-menopausal, ie, not meeting the criteria for being postmenopausal who are also receiving ongoing treatment with Luteinizing hormone-releasing hormone (LHRH) agonists (goserelin or leuprolide). The first injection should occur at least two weeks before study start.
• Documentation of ER-positive and/or PR-positive tumor (≥1% positive stained cells) based on most recent tumor biopsy (unless bone-only disease,discuss with study PI if results are discordant) utilizing an assay consistent with local standards.
• Documented human epidermal growth factor receptor 2 negative (HER2-) tumor based on local testing on most recent tumor biopsy: HER2-negative tumor is determined as immunohistochemistry score 0/1+ or negative by in situ hybridization (FISH/CISH/SISH) defined as a HER2/CEP17 ratio \<2 or for single probe assessment a HER2 copy number \<4.
• Must have received prior treatment with an Mechanistic target of rapamycin (mTOR) or phosphatidylinositol 3-kinase (PI3K) inhibitor
• Up to 2 prior lines of chemotherapy are allowed in the metastatic setting.
• Any number of lines of prior hormone therapy are allowed
• Patients with clear progression on either tamoxifen or fulvestrant should receive the alternate agent. Patients with clear progression on both drugs are not eligible.
• Ability to have a skin and tumor biopsy. Patients without accessible tumor for biopsy will be considered on a case by case basis.

You may not qualify if:

• Prior treatment with any cyclin-dependent kinase (CDK) inhibitor, and/or both fulvestrant and tamoxifen in the metastatic setting with clear progression.
• Patients with advanced/metastatic, symptomatic, visceral spread, at risk of life-threatening complications in the short term by investigator assessment.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before randomization .
• Current use of food or drugs known to be potent CYP3A4 inhibitors, drugs known to be potent CYP3A4 inducers (for examples, see the prohibited medications section), and drugs that are known to prolong the QT interval. See prohibited meds in appendix 5.
• Major surgery, chemotherapy, radiotherapy, or other anti-cancer therapy within 2 weeks before randomization.
• Any other malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.
• QTc interval \>480 msec (based on the mean value of the triplicate ECGs), family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation or Torsade de Pointes.
• QTc (Bazett) = QT/√RR
• Any of the following within 6 months prior to study enrollment: myocardial infarction, severe/unstable angina, ongoing cardiac dysrhythmias of NCI CTCAE Grade \>=2, symptomatic congestive heart failure, or cerebrovascular accident excluding transient ischemic attack.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of palbociclib, such as history of GI surgery with may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease or diarrhea of CTCAE v4.0 Grade \>1.
• Prior hematopoietic stem cell or bone marrow transplantation.
• Abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants (that cannot be safely held for biopsy) that would preclude tumor and skin biopsies.
• For fulvestrant: Ongoing anticoagulation that would preclude an IM injection
• For tamoxifen: Documented hypercoagulable state not receiving anticoagulation
• Known or possible hypersensitivity to palbociclib (CTCAE v4.0).

Sponsors & Collaborators

• University of California, San Francisco: lead
• Translational Breast Cancer Research Consortium: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (9)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Vanderbilt University

Nashville, Tennessee, 37240, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

palbociclib; Tamoxifen; Fulvestrant

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; 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: Dr. Hope Rugo, MD
• Organization: University of California, San Francisco

Hope.Rugo@ucsf.edu

(415) 353-7618

Study Officials

• Hope S Rugo, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: Professor

Study Record Dates

• First Submitted: February 10, 2015
• First Posted: March 10, 2015
• Study Start: October 19, 2015
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: March 16, 2022
• Results First Posted: March 16, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)