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

NCT02657928 | Completed Phase 2 Results DMC

• 3 other identifiers: MC1561NCI-2015-02181P30CA015083
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

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.

Conditions

Estrogen Receptor Positive; Postmenopausal; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Recurrent Uterine Corpus Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Alive and Free of Progression at 12 Weeks (PFS12)

  The percentage of patients who are progression-free at 12 weeks (PFS12) is defined as patients who are alive and progression free at 12 weeks. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator.

  At 12 weeks

Secondary Outcomes (5)

• Progression-free Survival

  From registration to the first of either disease progression or death from any cause, assessed up to 2 years

• Overall Survival

  From registration to death from any cause, assessed up to 2 years

• The Number of Patients With CA-125 Response

  Up to 2 years

• The Number of Patients With Confirmed Response (Complete Response or Partial Response)

  Up to 2 years

• The Number of Treatment-related Grade 3 or Higher Adverse Events

  Up to 30 days post-treatment

Other Outcomes (2)

• Creation of Patient Derived Xenograft Models for Future Translational Experiments

  28 days following treatment initiation

• Molecular Biomarkers Associated With a Response to Treatment With Letrozole and Ribociclib

  Baseline

Study Arms (1)

Treatment (ribociclib and letrozole)

EXPERIMENTAL

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.

Other: Laboratory Biomarker Analysis; Drug: Letrozole; Drug: Ribociclib

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ribociclib and letrozole)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Treatment (ribociclib and letrozole)

Ribociclib DRUG

Given PO

Also known as: LEE-011, LEE011

Treatment (ribociclib and letrozole)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• Colon-Otero G, Zanfagnin V, Hou X, Foster NR, Asmus EJ, Wahner Hendrickson A, Jatoi A, Block MS, Langstraat CL, Glaser GE, Dinh TA, Robertson MW, Camoriano JK, Butler KA, Copland JA, Weroha SJ. Phase II trial of ribociclib and letrozole in patients with relapsed oestrogen receptor-positive ovarian or endometrial cancers. ESMO Open. 2020 Oct;5(5):e000926. doi: 10.1136/esmoopen-2020-000926.

  PMID: 33109627 DERIVED

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Letrozole; ribociclib

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Fallopian Tube Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Gerardo Colon-Otero, MD
• Organization: Mayo Clinic

gcolonotero@mayo.edu

904/953-2000

Study Officials

• Gerardo Colon-Otero

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2016
• First Posted: January 18, 2016
• Study Start: July 8, 2016
• Primary Completion: May 21, 2018
• Study Completion: October 7, 2020
• Last Updated: October 26, 2021
• Results First Posted: October 18, 2019

Record last verified: 2021-10

Locations

US (3)