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Trial record 44 of 405 for:    LEVONORGESTREL

Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer

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ClinicalTrials.gov Identifier: NCT02397083
Recruitment Status : Recruiting
First Posted : March 24, 2015
Last Update Posted : September 27, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE March 18, 2015
First Posted Date  ICMJE March 24, 2015
Last Update Posted Date September 27, 2019
Actual Study Start Date  ICMJE September 23, 2015
Estimated Primary Completion Date September 30, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • Response rate (levonorgestrel intrauterine device [LIUD] alone) [ Time Frame: At 3 months ]
    Estimated with a 2-sided 90% confidence interval.
  • Response rate (levonorgestrel intrauterine device [LIUD] alone) [ Time Frame: 6 months ]
    Estimated with a 2-sided 90% confidence interval.
  • Response rate for levonorgestrel intrauterine device (LIUD) alone or in combination with everolimus after LIUD failure (i.e., failure to achieve complete response after initial 3 months of LIUD alone) [ Time Frame: 6 months ]
    Fisher's exact test will be used to compare response rates by 6 months between the LIUD alone arm and the LIUD plus everolimus arm. Estimated on each arm with a 2-sided 90% confidence interval.
Original Primary Outcome Measures  ICMJE
 (submitted: March 18, 2015)
Response Rate [ Time Frame: 6 months ]
Fisher's exact test used to compare response rates by 6 months between the LIUD alone arm and the LIUD + everolimus arm. Participants receive endometrial biopsy (EMB) to check the status of the disease.
Change History Complete list of historical versions of study NCT02397083 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2019)
  • Incidence of adverse events [ Time Frame: Up to 11 years ]
    Tabulated by treatment arm, severity, and relationship to study drug.
  • Progression free survival [ Time Frame: Up to 11 years ]
    Estimated using the Kaplan-Meier product-limit estimator. The log-rank test will be used to compare treatment arms.
  • Overall survival [ Time Frame: Up to 11 years ]
    Estimated using the Kaplan-Meier product-limit estimator. The log-rank test will be used to compare treatment arms.
  • Response duration [ Time Frame: Up to 4 weeks after completion of study treatment ]
    Estimated using the Kaplan-Meier product-limit estimator. The log-rank test will be used to compare treatment arms.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 18, 2015)
Overall survival [ Time Frame: 6 months ]
Kaplan-Meier product-limit estimator used to estimate overall survival, progression-free survival, and duration of response, and log-rank test to compare treatment arms.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Levonorgestrel-Releasing Intrauterine System With or Without Everolimus in Treating Patients With Atypical Hyperplasia or Stage IA Grade 1 Endometrial Cancer
Official Title  ICMJE Phase II Study of the Levonorgestrel Intrauterine Device Alone or in Combination With the mTORC1 Inhibitor, Everolimus, for the Treatment of Complex Atypical Hyperplasia and Stage Ia Grade 1 Endometrial Cancer
Brief Summary This randomized phase II trial studies how well levonorgestrel-releasing intrauterine system works when given alone or with everolimus in treating patients with atypical hyperplasia (a pre-cancerous growth of the lining of the uterus) or stage IA grade 1 endometrial cancer. The levonorgestrel-releasing intrauterine system is designed to prevent pregnancy by releasing a hormone called levonorgestrel, which is a type of progesterone. Progesterone is a common type of hormone that is used to prevent pregnancy and may prevent or slow tumor cell growth. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether the levonorgestrel-releasing intrauterine system works better with or without everolimus in treating patients with atypical hyperplasia or stage IA grade 1 endometrial cancer.
Detailed Description

PRIMARY OBJECTIVES:

I. Estimate the efficacy of the levonorgestrel intrauterine device (LIUD) (levonorgestrel-releasing intrauterine system) alone to treat complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial carcinoma with response rate.

II. Estimate the efficacy of the LIUD in combination with everolimus to treat LIUD-refractory complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial carcinoma with response rate.

SECONDARY OBJECTIVES:

I. Document the toxicity profile of the levonorgestrel intrauterine device alone or in combination with everolimus using the National Institutes of Health-National Cancer Institute (NIH-NCI) Common Terminology Criteria for Adverse Events version (v) 4.0.

II. Estimate overall survival (OS) and event-free survival (EFS) of patients with complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial cancer treated with the levonorgestrel IUD alone or in combination with everolimus.

III. Estimate the response duration associated with the levonorgestrel IUD alone or in combination with everolimus in patients with complex atypical hyperplasia or stage Ia grade 1 endometrioid endometrial cancer.

EXPLORATORY OBJECTIVE:

I. Determine if response to therapy can be predicted based on the molecular profile of the tumor, including estrogen-induced genes and relevant pathway members, or by change in gene expression after therapy.

OUTLINE:

Patients undergo placement of the LIUD on day 1. Patients achieving stable disease at 3 months are randomized to 1 of 2 treatment arms. Patients with complete response may continue treatment with the LIUD.

ARM I: Patients continue treatment with the LIUD for up to 9 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients continue treatment with the LIUD and receive everolimus orally (PO) once daily (QD) on days 1-28. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 6, 9, and 12 months and then every 6 months thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Atypical Endometrial Hyperplasia
  • FIGO Grade 1 Endometrial Endometrioid Adenocarcinoma
  • FIGO Grade 2 Endometrial Endometrioid Adenocarcinoma
Intervention  ICMJE
  • Drug: Everolimus
    Given PO
    Other Names:
    • 42-O-(2-Hydroxy)ethyl Rapamycin
    • Afinitor
    • Certican
    • RAD 001
    • RAD001
    • Votubia
    • Zortress
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Device: Levonorgestrel-Releasing Intrauterine System
    Placed in the uterus
    Other Name: Mirena
Study Arms  ICMJE
  • Experimental: Arm I (LIUD)
    Patients continue treatment with the LIUD for up to 9 months in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Device: Levonorgestrel-Releasing Intrauterine System
  • Experimental: Arm II (LIUD, everolimus)
    Patients continue treatment with the LIUD and receive everolimus PO QD on days 1-28. Treatment repeats every 28 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: Everolimus
    • Other: Laboratory Biomarker Analysis
    • Device: Levonorgestrel-Releasing Intrauterine System
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: March 18, 2015)
270
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 30, 2026
Estimated Primary Completion Date September 30, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • All patients with a diagnosis of complex atypical hyperplasia OR, grade 1 endometrioid OR focal grade 2 adenocarcinoma in predominately grade 1 disease endometrial carcinoma on endometrial biopsy or dilation and curettage (D & C) within three months of study enrollment
  • Prior progesterone treatment is ALLOWED
  • Ability to comply with endometrial biopsies every 3 months
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
  • Platelets >= 100 x 10^9/L
  • Hemoglobin (Hb) > 9 g/dL
  • Total serum bilirubin =< 2.0 mg/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN)
  • International normalized ratio (INR) =< 2; factor 10A drawn if patient on anticoagulant Eliquis
  • Serum creatinine =< 1.5 x ULN
  • Fasting serum cholesterol =< 300 mg/dL OR =< 7.75 mmol/L AND fasting triglycerides =< 2.5 x ULN; NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
  • Signed informed consent obtained prior to any screening procedures

Exclusion Criteria:

  • Patients with grade 2-3 endometrioid, uterine serous, clear cell, mucinous, squamous, transitional cell, sarcomas, or carcinosarcoma histology
  • Evidence of extrauterine spread of disease on imaging or during surgical evaluation
  • Patients who have prior therapy with everolimus or any other mammalian target of rapamycin (mTOR) inhibitor
  • Patients currently receiving anticancer therapies (including chemotherapy, radiation therapy, hormonal, or antibody-based therapy); prior treatment should have a washout period of 28 days or 4 1/2 half-lives (7 days), whichever is shorter
  • Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
  • Known intolerance or hypersensitivity to progesterone or its excipients
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus (e.g., inability to take oral medication or a requirement for intravenous [IV] alimentation, prior surgical procedures affecting absorption, malabsorption syndrome, and active peptic ulcer disease) are excluded; subjects with ulcerative colitis, inflammatory bowel disease, or a partial or complete small bowel obstruction are also excluded, as are any patients who cannot swallow the capsule whole
  • Uncontrolled diabetes mellitus as defined by hemoglobin A1c (HbA1c) > 8% despite adequate therapy; 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
  • Patients who have any severe and/or uncontrolled medical conditions such as: a) unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction =< 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; b) symptomatic congestive heart failure of New York Heart Association class III or IV; c) active (acute or chronic) or uncontrolled severe infection (not responding to antibiotics), liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus-deoxyribonucleic acid [HBV-DNA] and/or positive hepatitis B surface antigen [HbsAg], quantifiable hepatitis C virus-ribonucleic acid [HCV-RNA]); d) 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); e) active, bleeding diathesis
  • Chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed
  • Patients who have a known history of human immunodeficiency virus (HIV) seropositivity
  • Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; 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
  • Other malignancies within the past 3 years except for basal or squamous cell carcinoma of the skin
  • Active (acute or chronic) or uncontrolled severe infections (not responding to antibiotics), including acute pelvic inflammatory disease
  • Congenital or acquired uterine anomaly which distorts the uterine cavity
  • Genital actinomycosis
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
  • Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
  • Women who are pregnant or nursing (lactating) women
  • Women of child-bearing potential (WOCBP), defined as women physiologically capable of becoming pregnant, must use one additional highly effective methods of contraception in addition to the LIUD during the study and 8 weeks after; acceptable effective contraception methods include combo of the following: a) barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository; b) total abstinence or; c) male/female sterilization; women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation > six weeks prior to randomization
  • Women who are on contraindicated medications to everolimus must have confirmation from their physician that they may change or discontinue the medication if randomized to the LIUD + everolimus arm
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shannon Westin 713-794-4314 swestin@mdanderson.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02397083
Other Study ID Numbers  ICMJE 2014-0944
NCI-2015-00919 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2014-0944 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
P50CA098258 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Shannon N Westin M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP