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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02384239
Recruitment Status : Recruiting
First Posted : March 10, 2015
Last Update Posted : January 25, 2018
Information provided by (Responsible Party):
Hope Rugo, MD, University of California, San Francisco

Brief Summary:

Approximately 70 patients with HR+ advanced breast cancer will be enrolled. All patients will receive either fulvestrant (500 mg IM every 2 weeks x 3 then every four weeks) or tamoxifen (20 mg PO daily by physician choice). Pre-menopausal women must be in chemical menopause.

Arm 1 will receive palbociclib 100 mg qd, days 1-21 every 28 days. Arm 2 will receive palbociclib 125 mg qd, days 1-21 every 28 days. Restaging will be performed every 8 weeks. Therapy will be continued until PD or unacceptable toxicity.

Patients will be randomly allocated in a 1:1 ratio to take either 100 mg or 125 mg of palbociclib. Randomized treatment assignments will be made by permuted blocks, generated by our collaborating statistician at Dana-Farber Cancer Institute.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Hormone Receptor Positive Drug: Palbociclib Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Palbociclib in Combination With Fulvestrant or Tamoxifen as Treatment for Hormone Receptor Positive Metastatic Breast Cancer Previously Exposed to Inhibitors of the PI3K Pathway: A Phase II Study With Pharmacodynamics Markers
Study Start Date : October 2015
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : August 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Palbociclib 100mg
Treatment arm palbociclib dose 100mg + fulvestrant or tamoxifen
Drug: Palbociclib
Other Name: Ibrance

Experimental: Palbociclib 125mg
Treatment arm palbociclib dose 125mg + fulvestrant or tamoxifen
Drug: Palbociclib
Other Name: Ibrance

Primary Outcome Measures :
  1. Tumor Progression as measured by RECIST 1.1 [ Time Frame: 16 weeks ]
    Measured by RECIST 1.1

Secondary Outcome Measures :
  1. Progression-free Survival [ Time Frame: 24 months ]
    Number of months without progression as defined by RECIST 1.1

  2. RB phosphorylation in skin [ Time Frame: Baseline ]
    Skin biopsy lab measurement

  3. RB phosphorylation in tumor [ Time Frame: Baseline ]
    Tissue biopsy lab measurement

  4. Clinical Benefit Rate [ Time Frame: Up to 24 months ]
    Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) or stable disease (SD).

  5. Number of Adverse Events [ Time Frame: Every four weeks ]

  6. Tumor markers of resistance [ Time Frame: Baseline ]
    Measured by circulating plasma DNA

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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 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 HER2-negative 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 mTOR or 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.
  • Patients who cannot be biopsied will not be replaced (although up to 5 ineligible/inevaluable patients can be replaced)
  • A patient without biopsy amenable tumor must be cleared by the PI of the study; up to 10 patients without biopsy amenable tumor will be allowed in each arm of the study.
  • Patients without accessible tumor for biopsy must provide archived tumor from the most recent biopsy available
  • Bone marrow, hepatic, and renal function as follows:

Adequate bone marrow function:

  • leukocytes > 2500/mL
  • absolute neutrophil count > 1,000/mL
  • platelets > 100,000/mL"

Adequate hepatic function:

  • total bilirubin within normal institutional limits (unless Gilbert's disease with elevated indirect bilirubin only)
  • AST(SGOT) < 2.5 X institutional upper limit of normal
  • ALT(SGPT) < 2.5 X institutional upper limit of normal
  • Adequate renal function:
  • creatinine within normal institutional limits
  • Measurable or evaluable disease as defined by RECIST version 1.1. Tumor lesions previously irradiated or subjected to other loco-regional therapy will only be deemed measurable if progression at the treated site after completion of therapy is clearly documented.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Resolution of acute toxic effects of prior therapy or surgical procedures to National Cancer Institute (NCI) CTCAE Grade ≤1 (except alopecia)
  • Ability to understand a written informed consent document, and the willingness to sign it

Exclusion Criteria:

  • Prior treatment with any 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).
  • Known human immunodeficiency virus infection.
  • Other severe acute or chronic medical or psychiatric condition, including recent or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Participation in other studies involving investigational drug(s) (Phases 1-4) within 2 weeks before randomization the current study.
  • Women should not become pregnant or breastfeed whilst on this study. Birth control methods are acceptable and will be discussed with study participants.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02384239

Contact: Hope S Rugo, MD 415 353-7618
Contact: Amy N DeLuca, B.S 415-353-7288

United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94143
Contact: Amy DeLuca    415-353-7288   
Contact: Ivy Wong    415-353-7873   
Principal Investigator: Hope Rugo, M.D.         
United States, District of Columbia
Georgetown University Recruiting
Washington, District of Columbia, United States, 20007
Contact: Nellie Novielli    202-784-3923   
Contact: Julie Castle    202-687-2209   
Principal Investigator: Claudine Issacs, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Nana Owusu    773-702-2065   
Contact: Glenna Smith    773-834-2143   
Principal Investigator: Rita Nanda, MD         
United States, Indiana
Indiana University Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Robbie Comito    317-274-0935   
Principal Investigator: Anna Maria Storniolo, MD         
United States, Maryland
Johns Hopkins University Recruiting
Baltimore, Maryland, United States, 21287
Contact: Bridget Walsh    410-502-3613   
Principal Investigator: Vered Stearns, MD         
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Lauren Fisher    617-632-4321   
Contact: Nicole Ryabin    617-632-6767   
Principal Investigator: Erica Mayer, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Richelle Pelton    734-763-2960   
Principal Investigator: Catherine Van Poznak, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37240
Contact: Mikala Barnes    615-875-0072   
Contact: Kathleen Sanders    615-343-4091    kathleen.sanders@Vanderbilt.Edu   
Principal Investigator: Ingrid Mayer, MD         
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Claudette Foreman    713-798-7315   
Contact: Anne Pavlick    713-798-7814   
Principal Investigator: Polly Niravath, MD         
Sponsors and Collaborators
University of California, San Francisco

Responsible Party: Hope Rugo, MD, Professor, University of California, San Francisco Identifier: NCT02384239     History of Changes
Other Study ID Numbers: 147522
NCI-2015-01791 ( Registry Identifier: Clinical Trials Reporting Program )
First Posted: March 10, 2015    Key Record Dates
Last Update Posted: January 25, 2018
Last Verified: January 2018

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Estrogen Receptor Antagonists
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action