Clinical Trials /

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

NCT02283658

Description:

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.

Related Conditions:
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Unknown status

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Everolimus and Letrozole in Treating Patients With Recurrent Hormone Receptor Positive Ovarian, Fallopian Tube, or Primary Peritoneal Cavity Cancer
  • Official Title: A Phase 2 Trial of Letrozole and Everolimus in Relapsed Hormone Receptor Positive Ovarian, Fallopian Tube or Primary Peritoneal Carcinomas

Clinical Trial IDs

  • ORG STUDY ID: MC1464
  • SECONDARY ID: NCI-2014-02203
  • SECONDARY ID: MC1464
  • SECONDARY ID: P30CA015083
  • NCT ID: NCT02283658

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

Interventions

DrugSynonymsArms
Everolimus42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001Treatment (everolimus and letrozole)
LetrozoleCGS 20267, FemaraTreatment (everolimus and letrozole)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      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.

      SECONDARY OBJECTIVES:

      I. Cancer antigen (CA)-125 response, 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
      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.

      OUTLINE:

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (everolimus and letrozole)ExperimentalPatients 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.
  • Everolimus
  • Letrozole

Eligibility Criteria

        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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Proportion of patients alive and PFS12
Time Frame:12 weeks
Safety Issue:
Description: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

Measure:CA-125 response, defined as a 50% or greater reduction in baseline CA-125
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Confirmed response rate, estimated using RECIST 1.1 criteria
Time Frame:Up to 24 weeks
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:OS
Time Frame:Time from registration to death from any cause, assessed up to 2 years
Safety Issue:
Description:OS will be estimated using the method of Kaplan-Meier.
Measure:PFS
Time Frame:Time from registration to the first of either disease progression or death from any cause, assessed up to 2 years
Safety Issue:
Description:PFS will be estimated using the method of Kaplan-Meier.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Mayo Clinic

Last Updated