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Metastatic Breast CancerPhase 2NCT02384239

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

A Phase 2 study testing Palbociclib, Tamoxifen and Fulvestrant in people with Metastatic Breast Cancer and Hormone Receptor Positive, run by University of California, San Francisco at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Palbociclib, Tamoxifen and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
9 sitesUnited States
Study dates
19 Oct 2015to 31 Jan 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • Medically confirmed ovarian failure.
  • OR
  • 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.
  • 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)
  • aspartate aminotransferase (AST) / (serum glutamic-oxaloacetic transaminase (SGOT) < 2.5 X institutional upper limit of normal
  • alanine aminotransferase (ALT) / (serum glutamic-pyruvic transaminase (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

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of Chicago

    Chicago, Illinois, 60637

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Vanderbilt University

    Nashville, Tennessee, 37240

  • University of California, San Francisco

    San Francisco, California, 94143

  • Georgetown University

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

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

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.

Read the detailed description

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.

PRIMARY OBJECTIVES:

  1. To evaluate the incidence of grade 3/4 neutropenia in patients with hormone receptor positive (HR+) advanced breast cancer previously exposed to chemotherapy, treated with fulvestrant or tamoxifen (tamoxifen citrate) in combination with palbociclib at a dose of 100mg or 125mg.

SECONDARY OBJECTIVES:

  1. To evaluate progression-free survival with 100 mg and 125 mg dosing of palbociclib.

II. To evaluate inhibition of retinoblastoma (RB) phosphorylation in tumor and in skin at 100 mg and 125 mg dosing of palbociclib.

III. To evaluate the correlation between inhibition of RB phosphorylation in skin and tumor.

IV. To evaluate the correlation between inhibition of RB phosphorylation and progression-free survival (PFS).

  1. To evaluate the objective response and clinical benefit rate of palbociclib given at 100 mg or 125 mg.

VI. To evaluate the toxicity associated with palbociclib given at 100 mg and 125 mg in combination with fulvestrant or tamoxifen.

VII. To evaluate markers of resistance to palbociclib and fulvestrant or tamoxifen in circulating plasma tumor deoxyribonucleic acid (DNA) (ptDNA).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive low-dose palbociclib orally (PO) on days 1-21. Patients also receive tamoxifen citrate PO on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of cycle 1 and then on day 1 only in subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive high-dose palbociclib PO on days 1-21. Patients also receive tamoxifen citrate PO on days 1-28 or fulvestrant IM on days 1 and 15 of cycle 1 and then on day 1 only in subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PalbociclibDrug

    Also called Ibrance

    Given orally (PO)

  • TamoxifenDrug

    Also called Tamoxifen 20mg

    Given orally (PO)

  • FulvestrantDrug

    Also called Faslodex

    Given by intramuscular (IM) injection.

Study groups in NCT02384239
Study groupRoleWhat they receive
Palbociclib 100mg and, fulvestrant or tamoxifenExperimentalPalbociclib 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)
Receives: Drug: Palbociclib; Drug: Tamoxifen; Drug: Fulvestrant
Palbociclib 125mg and, fulvestrant or tamoxifenExperimentalPalbociclib 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)
Receives: Drug: Palbociclib; Drug: Tamoxifen; Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 24 months

Secondary outcomes (6)

  1. Progression-free Survival (PFS)

    PFS defined as the interval from study entry to the first documented evidence of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as at least a 20% increase in the sum of the longest diameter (SLD) of target lesions, taking as reference the smallest sum SLD recorded since the treatment started and minimum 5 mm increase over the nadir, or the appearance of one or more new lesions. Patients who remain progression-free at the time of analysis will be censored at their last date of follow-up.

    Measured: Up to 24 months

  2. Proportion of Participants With Demonstrated Clinical Benefit

    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) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

    Measured: 24 weeks

  3. Proportion of Participants With an Objective Response

    Defined as the proportion of patients whose best overall response, according to RECIST, is either complete response (CR), a partial response (PR) at 24 weeks. Only those patients who have measurable disease present at baseline, have received at least one cycle of therapy, and have had their disease re-evaluated will be considered evaluable for response.

    Measured: 24 weeks

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

    Median change in percent positive cells of Ki-67 from baseline will be reported with IQR

    Measured: Up to 24 months

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

    Median change in percent positive cells of Total-Rb from baseline will be reported with interquartile range (IQR)

    Measured: Up to 24 months

  6. Median Change in Percent Positive Cells From Baseline of pS780-Rb

    Median change in percent positive cells of pS780-Rb from baseline will be reported with IQR

    Measured: Up to 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2015 (estimated)
  2. Study start19 Oct 2015
  3. Primary completion31 Jan 2021
  4. Study completion31 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02384239
Sponsor's protocol ID
147522
Other IDs
NCI-2015-01791
Status last verified
Feb 2022
First submitted
10 Feb 2015
Last updated
16 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Palbociclib, Tamoxifen and Fulvestrant in people with Metastatic Breast Cancer and Hormone Receptor Positive, run by University of California, San Francisco at 9 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Grade 3 or 4 Neutropenia (time frame: Up to 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02384239.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2022.

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