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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02283658
Recruitment Status : Unknown
Verified March 2017 by Mayo Clinic.
Recruitment status was:  Active, not recruiting
First Posted : November 5, 2014
Last Update Posted : March 6, 2018
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
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 Drug: Everolimus Other: Laboratory Biomarker Analysis Drug: Letrozole Phase 2

Detailed Description:


I. Demonstrate that the combination of letrozole and everolimus leads to a higher percentage of patients who are free of progression at 12 weeks (PFS 12) as compared with that observed in a previously reported phase 2 trial of letrozole alone for relapsed ovarian carcinomas.


I. Cancer antigen (CA)-125 response, progression-free survival (PFS), overall survival (OS), the confirmed response rate, and adverse events.


I. Identify molecular biomarkers associated with a response to treatment with letrozole and everolimus in patients with relapsed ovarian carcinomas.

II. Develop and determine if response rates to letrozole and everolimus in patient derived xenograft (PDX) avatars correlate to responses noted in the patients.


Patients receive everolimus orally (PO) once daily (QD) and letrozole PO QD 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 6 months for 2 years.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Trial of Letrozole and Everolimus in Relapsed Hormone Receptor Positive Ovarian, Fallopian Tube or Primary Peritoneal Carcinomas
Study Start Date : November 2014
Estimated Primary Completion Date : November 2018
Estimated Study Completion Date : November 2018

Arm Intervention/treatment
Experimental: Treatment (everolimus and letrozole)
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
Given PO
Other Names:
  • 42-O-(2-Hydroxy)ethyl Rapamycin
  • Afinitor
  • Certican
  • RAD 001
  • RAD001

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Letrozole
Given PO
Other Names:
  • CGS 20267
  • Femara

Primary Outcome Measures :
  1. Proportion of patients alive and PFS12 [ Time Frame: 12 weeks ]
    The proportion 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.

Secondary Outcome Measures :
  1. CA-125 response, defined as a 50% or greater reduction in baseline CA-125 [ Time Frame: Up to 2 years ]
    The treatment of letrozole and everolimus will be considered promising, based on CA-125, if the observed CA-125 response rate is 30% or more.

  2. Confirmed response rate, estimated using RECIST 1.1 criteria [ Time Frame: Up to 24 weeks ]
    A confirmed tumor response is defined to be either a complete response or partial response noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.

  3. Incidence of adverse events, graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 30 days post-treatment ]
    The maximum grade for each type of adverse event (AE) will be recorded for each patient, and frequency tables will be reviewed to determine AE patterns.

  4. OS [ Time Frame: Time from registration to death from any cause, assessed up to 2 years ]
    OS will be estimated using the method of Kaplan-Meier.

  5. PFS [ Time Frame: Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years ]
    PFS will be estimated using the method of Kaplan-Meier.

Other Outcome Measures:
  1. Expression of molecular biomarkers associated with a response to treatment with letrozole and everolimus in patients with relapsed ovarian carcinomas [ Time Frame: 28 days following treatment initiation ]
    The Fisher's Exact test will be used to measure the associations.

  2. Response rates to letrozole and everolimus in PDX avatars [ Time Frame: 28 days following treatment initiation ]
    Will determine if response rates to letrozole and everolimus in PDX avatars correlate to responses noted in the patients. The Fisher's Exact test will be used to measure the associations.

  3. Responsiveness of tumors to letrozole and everolimus [ Time Frame: 28 days following treatment initiation ]
    "Response" will be defined as tumors with at least a 50% reduction in tumor volume at study end. "Unresponsive" will be defined as tumors with less than 10% tumor volume reduction at study end. Intermediate values will be defined as "Stable". Tumor growth curves will be plotted graphically and notated to indicate the outcome status of the originating patients. End of study tumor volumes will be correlated with outcome status of the originating patient as well. The Fisher's Exact test will be used to measure the associations.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Patients currently receiving anticancer therapies or who have received anticancer therapies =< 4 weeks prior to registration (including chemotherapy, radiation therapy, antibody based therapy, etc.)
  • Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
  • Uncontrolled diabetes mellitus as defined by hemoglobin (Hb)A1c > 8% despite adequate therapy; note: patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
  • Chronic treatment with corticosteroids or other immunosuppressive agents; note: topical or inhaled corticosteroids are allowed
  • Patients who have received live attenuated vaccines =< 1 week prior to registration and during the study; note: patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
  • History of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
  • Prior therapy with everolimus or an aromatase inhibitor
  • Known brain metastasis
  • Active and chronic viral hepatitis (i.e. quantifiable serum hepatitis B virus [HBV]-deoxyribonucleic acid [DNA] and/or positive hepatitis B virus surface antigen [HBsAg], or quantifiable hepatitis C virus [HCV]-ribonucleic acid [RNA] in serum)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02283658

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United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
National Cancer Institute (NCI)
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Principal Investigator: Gerardo Colon-Otero Mayo Clinic

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Responsible Party: Mayo Clinic Identifier: NCT02283658     History of Changes
Other Study ID Numbers: MC1464
NCI-2014-02203 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC1464 ( Other Identifier: Mayo Clinic in Florida )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: November 5, 2014    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2017
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Endometrioid
Cystadenocarcinoma, Serous
Adenocarcinoma, Papillary
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms, Cystic, Mucinous, and Serous
Endometrial Neoplasms
Uterine Neoplasms
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents