Ribociclib and Letrozole in Treating Patients With Relapsed ER Positive Ovarian, Fallopian Tube, Primary Peritoneal, or Endometrial Cancer

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02657928
• Date of registration: 14/01/2016
• Prospective Registration: Yes
• Primary sponsor: Mayo Clinic
• Public title: Ribociclib and Letrozole in Treating Patients With Relapsed ER Positive Ovarian, Fallopian Tube, Primary Peritoneal, or Endometrial Cancer
• Scientific 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.
• Date of first enrolment: July 8, 2016
• Target sample size: 40
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/show/NCT02657928
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Gerardo Colon-Otero
• Affiliation: Mayo Clinic

Key inclusion & exclusion 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


Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Postmenopausal

Recurrent Fallopian Tube Carcinoma

Estrogen Receptor Positive

Recurrent Primary Peritoneal Carcinoma

Recurrent Ovarian Carcinoma

Recurrent Uterine Corpus Carcinoma

Intervention(s)

Drug: Letrozole

Other: Laboratory Biomarker Analysis

Drug: Ribociclib

Primary Outcome(s)

Percentage of Patients Alive and Free of Progression at 12 Weeks (PFS12) [Time Frame: At 12 weeks]

Secondary Outcome(s)

The Number of Patients With CA-125 Response [Time Frame: Up to 2 years]

The Number of Treatment-related Grade 3 or Higher Adverse Events [Time Frame: Up to 30 days post-treatment]

Progression-free Survival [Time Frame: From registration to the first of either disease progression or death from any cause, assessed up to 2 years]

Overall Survival [Time Frame: From registration to death from any cause, assessed up to 2 years]

The Number of Patients With Confirmed Response (Complete Response or Partial Response) [Time Frame: Up to 2 years]

Secondary ID(s)

NCI-2015-02181

P30CA015083

MC1561

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Cancer Institute (NCI)

Results

• Results available: Yes
• Date Posted: 18/10/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02657928