Brief Title
Ribociclib and Letrozole in Treating Patients With Relapsed ER Positive Ovarian, Fallopian Tube, Primary Peritoneal, or Endometrial Cancer
Official Title
A Phase 2 Trial of Ribociclib (LEE011) and Letrozole in ER Positive Relapsed Ovarian Cancer, Fallopian Tube Cancer, Primary Peritoneal Carcinomas, and Endometrial Cancers.
Brief Summary
This phase II trial studies how well ribociclib and letrozole work in treating patients with
estrogen receptor (ER) positive ovarian, fallopian tube, primary peritoneal, or endometrial
cancer that has returned (come back) after a period of improvement. Ribociclib may stop the
growth of tumor cells by blocking some enzymes needed for cell growth. Cancer cells that are
estrogen receptor positive may need estrogen to grow. Letrozole lowers the amount of estrogen
made by the body and this may stop the growth of tumor cells that need estrogen to grow.
Giving ribociclib together with letrozole may be an effective treatment in patients with
ovarian, fallopian tube, primary peritoneal, or endometrial cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. Demonstrate if the combination of letrozole and ribociclib (LEE011) leads to a higher
percentage of patients who are progression free at 12 weeks (PFS 12) as compared with that
observed in prior studies with single agent letrozole.
SECONDARY OBJECTIVES:
I. Demonstrate if the combination of letrozole and ribociclib (LEE011) leads to a higher
cancer antigen 125 (CA-125) response rate in patients with relapsed ER positive ovarian
cancers and endometrial cancers as compared to that observed in previously reported single
agent letrozole studies.
II. Median progression-free survival (PFS), overall survival (OS), the confirmed response
rate, and adverse events.
TERTIARY OBJECTIVES:
I. Identify molecular biomarkers associated with a response to treatment with letrozole and
ribociclib (LEE011) (in patients with relapsed ovarian carcinomas and endometrial cancers).
II. Develop patient derived xenograft (PDX) avatars on tumors from participants for possible
future translational study evaluating a potential correlation between responses in the PDX
model to patients' responses.
OUTLINE:
Patients receive ribociclib orally (PO) daily and letrozole PO daily on days 1-28. Courses
repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3-6 months for 2 years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Percentage of Patients Alive and Free of Progression at 12 Weeks (PFS12)
Secondary Outcome
Progression-free Survival
Condition
Estrogen Receptor Positive
Intervention
Laboratory Biomarker Analysis
Study Arms / Comparison Groups
Treatment (ribociclib and letrozole)
Description: Patients receive ribociclib PO daily and letrozole PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
40
Start Date
July 8, 2016
Completion Date
July 1, 2021
Primary Completion Date
May 21, 2018
Eligibility Criteria
Inclusion Criteria:
- Ability to understand and the willingness to sign a written informed consent document
- Post-menopausal
- Histologically confirmed recurrent ovarian, fallopian tube or primary peritoneal
carcinoma or endometrial cancer in post-menopausal women; NOTE: pure clear cell and
pure mucinous carcinomas are ineligible; platinum sensitive, platinum resistant and
platinum refractory disease are eligible; no limitations in the number of prior
regimens
- Patient has disease amenable to biopsy and is agreeable to undergo a biopsy; NOTE:
under unusual circumstances, submission of ascites material may be acceptable if a
biopsy is not possible; this exception will require approval by one of the study
principal investigators
- Willing to provide tissue samples for ER and retinoblastoma (RB) staining
- Measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST) criteria
- Tumors must stain positive for estrogen receptor (>= 10%) by immunohistochemistry
(IHC)
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
- Absolute neutrophil count (ANC) >= 1000/mm^3
- Platelet count >= 100,000/mm^3
- Hemoglobin >= 9.0 g/dL
- Total bilirubin =< 1 x upper limit of normal (ULN); or total bilirubin =< 3.0 x ULN
with direct bilirubin =< 1.5 x ULN in patients with well-documented Gilbert's syndrome
- Aspartate transaminase (aspartate aminotransferase [AST]) =< 2.5 x ULN (=< 5 x ULN in
patients with liver metastasis)
- International normalized ratio (INR) =< 2
- Creatinine =< 1.5 mg/dL
- Potassium =< ULN (or corrected to =< ULN with supplements prior to registration)
- Total calcium (corrected for serum calcium) =< ULN (or corrected to =< ULN with
supplements prior to registration)
- Magnesium =< ULN (or corrected to =< ULN with supplements prior to registration)
- Sodium =< ULN (or corrected to =< ULN with supplements prior to registration)
- Phosphorus =< ULN (or corrected to =< ULN with supplements prior to registration)
- Ability to swallow study medication
- Provide informed written consent
- Willing to return to enrolling institution for follow-up (during the active monitoring
phase of the study)
- Willing to provide tissue samples for correlative research purposes
Exclusion Criteria:
- Patients who have central nervous system (CNS) involvement unless they meet ALL of the
following criteria:
- >= 4 weeks from prior therapy completion (including radiation and/or surgery) to
starting the study treatment
- Clinically stable CNS tumor at the time of screening and not receiving steroids
and/or enzyme-inducing anti-epileptic medications for brain metastases
- Patient has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, cause unacceptable safety risks, contraindicate
patient participation in the clinical study or compromise compliance with the protocol
(e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled
fungal, bacterial or viral infections, etc.)
- Clinically significant, uncontrolled heart disease or cardiac repolarization
abnormalities and/or recent events including any of the following:
- History of acute coronary syndromes (including myocardial infarction, unstable
angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
symptomatic pericarditis within 6 months prior to screening
- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)
- Documented cardiomyopathy
- Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated
acquisition (MUGA) scan or echocardiogram (ECHO) at screening
- Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia),
complete left bundle branch block, high-grade atrioventricular (AV) block (e.g.
bifascicular block, Mobitz type II and third-degree AV block) long QT syndrome or
family history of long QT syndrome
- Idiopathic sudden death or congenital long QT syndrome
- Risk factors for torsades de pointe (TdP) including uncorrected hypokalemia or
hypomagnesemia, history of cardiac failure, or history of clinically
significant/symptomatic bradycardia
- Concomitant use of medication(s) with a known risk to prolong the QT interval
and/or known to cause torsades de pointe that cannot be discontinued (within 5
half-lives or 7 days prior to starting study drug) or replaced by safe
alternative medication
- Inability to determine the QT interval on screening (corrected QT interval
[QTcF], using Fridericia's correction)
- Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening
- Bradycardia (heart rate < 50 at rest), by electrocardiogram (ECG) or pulse, at
screening
- Tachycardia (heart rate > 110 at rest), by ECG or pulse at screening
- Inability to determine the QTcF interval on the ECG (i.e.: unreadable or not
interpretable) or QTcF > 450 msec (using Fridericia's correction); NOTE: all as
determined by screening ECG
- Patient is currently receiving any of the following medications and cannot be
discontinued =< 7 days prior to starting study drug: known strong inducers or
inhibitors of cytochrome P450 family 3, subfamily A, polypeptide 4/5 (CYP3A4/5)
including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges or
that have a narrow therapeutic window and are predominantly metabolized through
CYP3A4/5 or herbal preparations/medications or dietary supplements
- Patient is currently receiving or has received systemic corticosteroids within =< 2
weeks prior to starting study drug, or who have not fully recovered from side effects
of such treatment; NOTE: the following uses of corticosteroids are permitted: single
doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive
airways diseases), eye drops or local injections (e.g., intra-articular)
- Patient has received radiotherapy =< 4 weeks or limited field radiation for palliation
=< 2 weeks prior to starting study drug, and who has not recovered to grade 1 or
better from related side effects of such therapy (exceptions include alopecia) and/or
in whom >= 30% of the bone marrow was irradiated
- Patient has had major surgery =< 14 days prior to registration or has not recovered
from major side effects (tumor biopsy is not considered as major surgery)
- Known to be human immunodeficiency virus (HIV) positive (testing not mandatory)
- Patient has a known hypersensitivity to any of the excipients of ribociclib
- Patient is currently receiving warfarin or other Coumarin-derived anticoagulant for
treatment, prophylaxis or otherwise; NOTE: therapy with apixaban, dabigatran, heparin,
low molecular weight heparin (LMWH) or fondaparinux is allowed
- Participation in a prior investigational study within 30 days prior to enrollment or
=< 5 half-lives of the investigational product, whichever is longer
- Patient has not recovered from all toxicities related to prior anticancer therapies to
National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE)
version 4.0 grade < 3 (exception to this criterion: patients with any grade of
alopecia or neuropathy are allowed to enter the study)
- Patient with a Child-Pugh score B or C
- 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 significant small
bowel resection)
- Prior therapy with ribociclib or an aromatase inhibitor (letrozole, anastrozole or
exemestane)
- Patient has received systemic chemotherapy =< 3 weeks prior to registration
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Gerardo Colon-Otero, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02657928
Organization ID
MC1561
Secondary IDs
NCI-2015-02181
Responsible Party
Sponsor
Study Sponsor
Mayo Clinic
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Gerardo Colon-Otero, Principal Investigator, Mayo Clinic
Verification Date
May 2019