Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer

NCT02283658 | Completed Phase 2 Results DMC

• 3 other identifiers: MC1464NCI-2014-02203P30CA015083
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

This pilot, phase II trial studies how well everolimus and letrozole work in treating patients with hormone receptor positive ovarian, fallopian tube, or primary peritoneal cavity cancer that has come back. Everolimus and letrozole may stop the growth of tumor cells by blocking some the enzymes needed for cell growth.

Conditions

Ovarian Endometrioid Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Alive and Progression Free Survival at 12 Weeks

  The percentage of PFS12 successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true success proportion will be calculated according to the exact binomial method. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), Disease progression in evaluable patients will be defined as one or more of the following: * Any new disease and/or clear progression of evaluable disease; OR * 2 fold elevation in CA-125 from its lowest level (either initial level or nadir, whichever is lowest, since study enrollment) combined with CA-125 elevation confirmed by re-assay at any time.

  12 weeks

Secondary Outcomes (5)

• Percentage of Participants With CA-125 Response

  Up to 2 years

• Confirmed Response Rate, Estimated Using RECIST 1.1 Criteria

  Up to 24 weeks

• Number of Participants Experiencing Adverse Events

  Up to 30 days post-treatment

• Overall Suravival(OS)

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

• Progression Free Survival (PFS)

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

Other Outcomes (3)

• Expression of Molecular Biomarkers Associated With a Response to Treatment With Letrozole and Everolimus in Patients With Relapsed Ovarian Carcinomas

  28 days following treatment initiation

• Response Rates to Letrozole and Everolimus in PDX Avatars

  28 days following treatment initiation

• Responsiveness of Tumors to Letrozole and Everolimus

  28 days following treatment initiation

Study Arms (1)

Treatment (everolimus and letrozole)

EXPERIMENTAL

Patients receive everolimus PO QD and letrozole PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001

Treatment (everolimus and letrozole)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (everolimus and letrozole)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Treatment (everolimus and letrozole)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed estrogen receptor positive (greater than 10%) recurrent ovarian, fallopian tube or primary peritoneal carcinoma in post-menopausal women; note: pure clear cell and pure mucinous carcinomas are ineligible; both 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 will require approval by one of the study principal investigators
• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
• Absolute neutrophil count (ANC) \>= 1500/mm\^3
• Platelet count \>= 100,000/mm\^3
• Hemoglobin \> 9.0 g/dL
• Total serum bilirubin =\< 2 mg/dL
• Aspartate transaminase (AST) =\< 2.5 x upper limit of normal (ULN) (=\< 5 x ULN in patients with liver metastasis)
• International normalized ratio (INR) =\< 2
• Creatinine =\< 1.5 x ULN
• Fasting serum cholesterol =\< 300 mg/dL or =\< 7.75 mmol/L and fasting triglycerides =\< 2.5 x ULN; in case of any of these thresholds be exceeded, the patient can only be included after initiation of appropriate lipid lowering medications
• 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

You may not qualify if:

• Any of the following
• Pregnant women
• Nursing women
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens including but not limited to any of the following that would limit compliance with study requirements:
• Ongoing or active severe infection
• Liver disease such as cirrhosis
• Decompensated liver disease
• Symptomatic congestive heart failure (New York heart Association class III or IV)
• Unstable angina pectoris, serious uncontrolled cardiac arrhythmia, myocardial infarction =\< 6 months prior to registration
• Known severely impaired lung function (spirometry and diffusing capacity of the lung for carbon monoxide \[DLCO\] 50% or less of normal and oxygen \[O2\] saturation 88% or less at rest on room air)
• Active bleeding diathesis
• Psychiatric illness
• Known to be human immunodeficiency virus (HIV) positive
• Receiving any other investigational agent =\< 4 weeks prior to registration which would be considered as treatment for the primary neoplasm
• Other active malignancy =\< 3 years prior to registration; exceptions: non-melanotic skin cancer or carcinoma-in-situ of the cervix, uterus or breast; note: if there is a history of prior malignancy, they must not be receiving other specific treatment for their cancer

Sponsors & Collaborators

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

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms

Interventions

Everolimus; Letrozole

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)

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

Results Point of Contact

• Title: Gerardo Colon-Otero, M.D.
• 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: November 3, 2014
• First Posted: November 5, 2014
• Study Start: November 14, 2014
• Primary Completion: June 15, 2016
• Study Completion: June 21, 2018
• Last Updated: October 23, 2020
• Results First Posted: March 31, 2020

Record last verified: 2020-09

Locations

US (2)