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Metastatic Breast CancerPhase 2MAINTAINNCT02632045

Study of Efficacy of Ribociclib After Progression on CDK4/6 Inhibition in Patients With HR+ HER2- Advanced Breast Cancer

A Phase 2 study testing LEE-011 and Fulvestrant in people with Metastatic Breast Cancer and Breast Carcinoma, run by Melissa K Accordino at 13 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

This is a randomized trial for patients with metastatic hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have progressed on an aromatase inhibitor plus a CDK4/6 inhibitor (either palbociclib or ribociclib) to either fulvestrant alone or fulvestrant with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer, Breast Carcinoma
What is being tested?
LEE-011 and Fulvestrant
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
169 participants
Where
13 sitesUnited States
Study dates
Mar 2016to 4 Jan 2022
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

  • Men or women at least 18 years of age with histologically or cytologically confirmed adenocarcinoma of the breast with unresectable or metastatic disease.
  • Most recent tumor biopsy or surgical resection specimen must be either estrogen-receptor (ER) positive, progesterone receptors (PgR) positive, or both, as defined by immunohistochemistry (IHC) ≥1% (as per the American Society of Clinical Oncology (ASCO)-College of American Pathologists (CAP) guidelines).
  • HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+ (i.e. indeterminate), a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing. (as per the ASCO-CAP guidelines).
  • Postmenopausal status or receiving ovarian ablation with a GnRH agonist such as goserelin. Postmenopausal status ( is defined by any one of the following criteria:
  • Prior bilateral oophorectomy.
  • Age ≥60 years.
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  • Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and follicle stimulating hormone (FSH), luteinizing hormone (LH), and estradiol in the postmenopausal range per local normal If the patient does not meet criteria for postmenopausal status but is receiving ovarian ablation therapy with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin, the patient is eligible for this study, provided that the GnRH agonist is started at least 2 weeks prior to C1D1 of anti-estrogen therapy.
  • Have evidence of measurable or unmeasurable disease.
  • Eastern Cooperative Group (ECOG) performance status of 0 or 1.
  • No prior cdk 4/6 inhibitor (Closed to Accrual). If patient has not previously received letrozole, letrozole will be supplied by Novartis. If previously progressed on letrozole, another aromatase inhibitor that the patient has not previously received is allowed, per standard of care (anastrazole or exemestane, not supplied by study). Ribociclib will be supplied by Novartis. If patient has previously received letrozole, anastrazole, and exemestane, (s)he is not eligible. For scenario 1, patients are allowed to have started the aromatase inhibitor within 4 consecutive weeks prior to protocol registration. For instance, it is acceptable for patient who will be treated with letrozole in scenario #1, to have started letrozole within 4 consecutive weeks prior to protocol registration. No prior fulvestrant allowed.
  • Scenario 2: the patient must have received an aromatase inhibitor (letrozole, arimidex, exemestane) or tamoxifen or fulvestrant plus palbociclib as standard of care or received a CDK4/6 inhibitor (palbociclib or ribociclib or abemaciclib), and demonstrated evidence of disease progression. If the patient was enrolled in a randomized clinical trial involving ribociclib or abemaciclib or palbociclib (such as the MONALEESA or PALOMA series of trials), then it must be known after study discontinuation and unblinding that the patient received the investigational drug and not placebo. Ribociclib or abemaciclib or palbociclib can also be given as standard of care. Documentation of progression and duration of response on aromatase inhibitor or tamoxifen plus CDK 4/6 inhibitor should be provided whenever possible. If patient received prior fulvestrant, exemestane must be the hormone therapy backbone in the randomization. If patient received prior exemestane, fulvestrant must be the hormone therapy backbone in the randomization. If neither has been administered, selection of fulvestrant or exemestane in the randomization will be per investigator discretion.
  • Adequate baseline laboratory studies (hematologic and chemistry), including the following parameters:
  • Absolute neutrophil count ≥ 1500 per microliter, Platelets ≥ 75,000 per microliter, Hemoglobin level ≥ 8.0 gm/dL on screening complete blood count.
  • Potassium, sodium, total calcium (corrected only in the case of hypoalbuminemia), magnesium, and phosphorus within normal limits of the local laboratory (screening values can be rechecked after electrolyte repletion and before the first dose of study medication, if necessary).
  • Serum creatinine level ≤ 1.5 mg/dL or estimated glomerular filtration rate > 50 mL/min.
  • In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × the upper limit of normal (ULN). If the patient has liver metastases, ALT and AST should be < 5 × ULN.
  • Total bilirubin ≤ 1.5 x ULN. (In patients with well documented Gilbert's Syndrome, total bilirubin ≤ 3 × ULN with direct bilirubin within normal range.)
  • international normalized ratio (INR) ≤ 1.5
  • a) Written informed consent and HIPAA authorization obtained from the subject/legal representative prior to performing any protocol-related procedures b) Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
  • Must be able to swallow ribociclib and oral aromatase inhibitor, such as letrozole or exemestane.

Who cannot join

  • Patient has a known hypersensitivity to any of the excipients of ribociclib, aromatase inhibitors (such as letrozole) or fulvestrant
  • Active central nervous system (CNS) disease. History of CNS metastases or cord compression is allowable if the patient has been clinically stable for at least 4 weeks since completion of definitive treatment and is off systemic steroids. In the case of brain metastases, the patient must have stable or improved imaging at least 4 weeks after completion of definitive treatment. If there is evidence of active leptomeningeal disease, the patient is ineligible.
  • Identified as having visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis. Visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease.
  • Received more than 1 prior systemic chemotherapy in the unresectable or metastatic setting. If the patient received 1 prior systemic chemotherapy, the patient is eligible. Having received prior therapies for breast cancer (such as everolimus or experimental agents) does not affect eligibility for this study.
  • Completion of major surgery, chemotherapy, targeted therapy (such as everolimus or experimental agents_ or radiation within 14 days prior to starting investigational drug or has not recovered from major side effects. There is no required washout period from completion of prior anti-estrogen therapy (either scenario) or prior CDK 4/6 inhibitor (if scenario 2) to initiation of ribociclib/placebo and anti-estrogen on trial.
  • Residual acute toxic effects of prior anti-cancer therapy that have not resolved to CTCAE v.4 Grade ≤1. Exception to this criterion: patients with grade 1 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion, are allowed to enter the study.
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  • Presence of a concurrent malignancy or malignancy diagnosed within 5 years of randomization, with the exception of basal or squamous cell carcinoma, non-melanomatous skin cancer, curatively resected cervical cancer, localized prostate cancer treated with curative intent, and stage I colorectal cancer treated with curative resection.
  • Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patient has a known history of HIV infection (testing not mandatory).
  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including any of the following:
  • History of myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
  • Documented cardiomyopathy
  • Patient has a known Left Ventricular Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO).
  • Long QT syndrome or family history of long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
  • Risk factors for Torsades de Pointe (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesaemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia ii. Concomitant medications(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting study drug) iii. Inability to determine the QTc interval
  • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular block (e.g., bifascicular block, Mobitz type II and third degree Atrioventricular (AV) block)
  • Systolic Blood Pressure (SPB) >160 or <90 mmHg.
  • Corrected QT interval (QTcF) > 450 msec (QT interval using Fridericia's correction) on screening electrocardiogram. If QTc prolongation is felt to be related to electrolyte imbalance, an EKG can be repeated after correction of electrolytes. Mean resting heart rate 50-100 bpm (determined from ECG).
  • The presence of any other concurrent severe and/or uncontrolled medical condition that would, in the investigator or treating physician's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol. This includes uncontrolled infections that could potentially be exacerbated by anti-neoplastic treatment, active untreated or uncontrolled fungal bacterial or viral infections, etc.
  • Currently receiving treatment, including medications and herbal preparations, with known strong inducers or inhibitors of cytochrome p450 enzymes CYP3A4/5 medications that have a narrow therapeutic window and are predominately metabolized through CYP3A4/5 or herbal preparations/medications, dietary supplements, which cannot be discontinued prior to receiving investigational drug. Anti-retrovirals, anti-microbials, and anti-arrhythmics are the most common medications that interact with these enzyme. Please refer to Section 5: Pharmaceutical Information and Appendix B for more information and a list of drugs that should not be used concurrently with ribociclib.
  • Patients who are receiving any other investigational agents concurrently or have received investigational agents within 14 days or 5 half-lives of the compound or active metabolites, whichever is longer before the first dose of the study treatment.
  • 15 Patient is concurrently using hormone replacement therapy. 16. Subject is pregnant or nursing. Serum or urine Beta-Human chorionic gonadotropin (HCG) must be checked in all pre- and peri-menopausal patients. (Fulvestrant is pregnancy category D and CDK4/6 inhibitors have demonstrated teratogenicity/fetotoxicity in animal studies.)

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites
  • Northside Hospital, Inc.

    Atlanta, Georgia, 30342

  • University of Alabama at Birmingham (UAB)

    Birmingham, Alabama, 35294

  • Northwestern Medical Hospital

    Chicago, Illinois, 60611

  • Northwell Health/Monter Cancer Center

    Lake Success, New York, 11042

  • University of Wisconsin School of Medicine

    Madison, Wisconsin, 53792-001

  • Vanderbilt-Ingham Cancer Center

    Nashville, Tennessee, 37232

  • NYU Langone Medical Center

    New York, New York, 10016

  • Mount Sinai Medical Center

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032

  • Weill Cornell Medical Center

    New York, New York, 10065

  • Stony Brook Cancer Center

    Stony Brook, New York, 11794

  • Albert Einstein University / Montefiore Medical Center

    The Bronx, New York, 10461

  • The University of Kansas Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: A randoMized phAse II trIal of fulvestraNt wiTh or Without Ribociclib After Progression on AntI-estrogeN Therapy Plus Cyclin-dependent Kinase 4/6 Inhibition in Patients With Unresectable or Metastatic Hormone Receptor +, HER2 - Breast Cancer (MAINTAIN Trial)

This is a randomized trial for patients with metastatic hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have progressed on an aromatase inhibitor plus a CDK4/6 inhibitor (either palbociclib or ribociclib) to either fulvestrant alone or fulvestrant with ribociclib (LEE-011). The purpose of the trial is to determine whether there is continued benefit for patients to remain on a CDK4/6 inhibitor at the time of switching anti-estrogen therapy. As ribociclib and palbociclib have a similar toxicity and drug profile and mechanism of action, the investigators feel that it is appropriate for patients to receive either drug with an aromatase inhibitor prior to randomization.

Read the detailed description

Despite advances in early detection and therapeutic options, unresectable or metastatic breast cancer remains incurable and is one of the leading causes of cancer-related mortality. Breast cancer is a molecularly heterogeneous disease. This study will be evaluating estrogen receptor (ER) expression positivity and/or progesterone receptor (PgR) positivity of breast cancer with the absence of over-expression or amplification of HER2.

Inhibitors of the cyclin dependent kinases 4 and 6 (CDK4/6) have been developed and demonstrated impressive activity in patients with ER-positive HER2-negative breast cancer with marked improvements in progression free survival. This question is asking whether CDK 4/6 inhibition should be continued with hormone therapy in patients who will be switching their hormone therapy in the metastatic breast cancer setting.

Being tested
LEE-011, Fulvestrant, Placebo
Keywords
Breast Neoplasms, Breast Cancer, Breast Carcinoma, Breast tumors, Cancer of the Breast
Medical subject headings
Breast Neoplasms

What participants receive

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

  • LEE-011Drug

    Also called ribociclib

    600 mg capsule (3x 200 mg capsules)

  • FulvestrantDrug

    Also called Faslodex

    500 mg injection

  • PlaceboDrug

    Also called No other name

    600 mg capsule (3x 200 mg capsules)

Study groups in NCT02632045
Study groupRoleWhat they receive
Ribociclib (LEE-011)/FulvestrantExperimentalLEE-011 is administered orally, 600mg, daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Receives: Drug: LEE-011; Drug: Fulvestrant
Placebo/FulvestrantPlacebo comparatorPlacebo is administered orally, 600mg daily for 3 weeks and 1 week off. Fulvestrant is administered intramuscularly, 500mg, every 2 weeks x 3, then every 4 weeks.
Receives: Drug: Fulvestrant; Drug: Placebo

What is being measured

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

  1. Progression Free Survival (PFS)

    Progression free survival (PFS) is defined as the interval from the time of randomization until objective disease progression (local assessment) or death from any cause. Disease status will be assessed with comprehensive radiographic studies every three treatment cycles (approximately every 12 weeks (+/- 1 week)). Disease progression as assed by RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Measured: Up to approximately 30 months

Secondary outcomes (2)
  1. Overall Response Rate (ORR)

    Evaluation of disease will be made according to RECIST criteria (version 1.1) in patients with measurable disease. As this study will enroll patients with measureable and un-measurable disease as defined by RECIST v1.1, ORR will only be assessed in evaluable patients. ORR = complete response (disappearance of all target lesions; ny pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm) + partial response (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters).

    Measured: measured every 12 weeks, up to 6 months

  2. Clinical Benefit Rate (CBR)

    CBR defined as the number of participants with complete response (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm) + partial response (At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters) + stable disease (Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for disease progression, taking as reference the smallest sum of the diameters while on study) at ≥ 24 weeks of follow up per RESIST 1.1 criteria.

    Measured: Up to 24 weeks

Timeline

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

  1. First posted16 Dec 2015 (estimated)
  2. Study startMar 2016
  3. Primary completion4 Jan 2022
  4. Study completion4 Jan 2022

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
Double blind
Who is masked
Participant, Investigator
Enrolment
169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02632045
Sponsor's protocol ID
AAAP9506
Acronym
MAINTAIN
Status last verified
Dec 2024
First submitted
14 Dec 2015
Last updated
6 Dec 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LEE-011 and Fulvestrant in people with Metastatic Breast Cancer and Breast Carcinoma, run by Melissa K Accordino at 13 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 20 inclusion and 22 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 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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. Some participants in this study may receive a placebo. 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 6 Dec 2024). 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?

Progression Free Survival (PFS) (time frame: Up to approximately 30 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 6 Dec 2024.

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