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Phase II Study of Intrauterine Device (IUD) Alone or in Combination With Everolimus in Endometrial Cancer

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ClinicalTrials.gov Identifier: NCT02397083
Recruitment Status : Recruiting
First Posted : March 24, 2015
Last Update Posted : July 16, 2018
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

You are being asked to take part in this study because you have endometrial hyperplasia (a pre-cancerous growth of the lining of the uterus) and/or early-stage endometrial cancer.

The goal of this clinical research study is to learn if the Mirena intrauterine device (levonorgestrel IUD), alone or in combination with everolimus, is effective for the treatment of endometrial hyperplasia and/or early-stage endometrial cancer.

This is an investigational study. The levonorgestrel IUD is commercially available and FDA approved as a form of birth control. The use of the IUD itself to treat endometrial cancer is investigational. Everolimus is FDA approved and commercially available to treat kidney, breast, and pancreatic cancers. The combination of everolimus and the levonorgestrel IUD in this study to treat endometrial cancer is investigational.

Up to 270 patients will be enrolled in this study. Up to 250 will take part at MD Anderson and up to 20 will take part at the Harris Health System.


Condition or disease Intervention/treatment Phase
Endometrial Cancer Device: Levonorgestrel Intrauterine Device (LIUD) Drug: Everolimus Behavioral: Questionnaire Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 2015
Estimated Primary Completion Date : September 2026
Estimated Study Completion Date : September 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Levonorgestrel Intrauterine Device (LIUD)

Participants undergo treatment with the LIUD. Placement of LIUD done at the time of the dilation and curettage (D&C) or during a routine clinic visit.

At 3 months after procedure, participants whose disease has completely responded to treatment, randomized to remain on study for 3 more months using LIUD alone.

Quality of life (QOL) questionnaire completed at baseline visit.

Device: Levonorgestrel Intrauterine Device (LIUD)
Participants undergo treatment with the LIUD. Placement of LIUD done at the time of the dilation and curettage (D&C) or during a routine clinic visit.
Other Names:
  • LIUD
  • Intrauterine device
  • IUD
  • Mirena Levonorgestrel Intrauterine device

Behavioral: Questionnaire
Quality of life (QOL) questionnaire completed at baseline visit.
Other Name: Survey

Experimental: Levonorgestrel Intrauterine Device (LIUD) + Everolimus

Participants undergo treatment with the LIUD. Placement of LIUD done at the time of the dilation and curettage (D&C) or during a routine clinic visit.

At 3 months after procedure, participants whose disease has completely responded to treatment, randomized to continue the LIUD in combination with Everolimus. Everolimus administered at 10 mg taken by mouth daily for three months.

Quality of life (QOL) questionnaire completed at baseline visit.

Device: Levonorgestrel Intrauterine Device (LIUD)
Participants undergo treatment with the LIUD. Placement of LIUD done at the time of the dilation and curettage (D&C) or during a routine clinic visit.
Other Names:
  • LIUD
  • Intrauterine device
  • IUD
  • Mirena Levonorgestrel Intrauterine device

Drug: Everolimus
At 3 months after LIUD procedure, participants receive Everolimus administered at 10 mg taken by mouth daily for three months.
Other Names:
  • Afinitor
  • Zortress
  • RAD001

Behavioral: Questionnaire
Quality of life (QOL) questionnaire completed at baseline visit.
Other Name: Survey




Primary Outcome Measures :
  1. Response Rate [ Time Frame: 6 months ]

    Progressive disease (PD) defined as presence of grades 2 or 3 endometrioid adenocarcinoma or presence of serous, clear cell or carcinosarcoma histology types. Complete response (CR) defined as no evidence of cancer or atypia on specimen. Simple or complex hyperplasia without atypia considered a CR.

    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.



Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 6 months ]
    Kaplan-Meier product-limit estimator used to estimate event-free survival (EFS) and overall survival (OS), and duration of response, and log-rank test used to compare treatment arms.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. All patients with a diagnosis of complex atypical hyperplasia OR grade 1 endometrioid endometrial carcinoma on endometrial biopsy or D & C within three months of study enrollment
  2. Prior progesterone treatment for either diagnosis is ALLOWED.
  3. Ability to comply with endometrial biopsies every 3 months
  4. Age >/= 18 years
  5. ECOG performance status </= 2
  6. Adequate bone marrow function as shown by: absolute neutrophil count (ANC) >/= 1.5 x 10^9/L; Platelets >/=100 x 10^9/L; Hb >9 g/dL;
  7. Adequate liver function as shown by: a) Total serum bilirubin </= 2.0 mg/dL; b) Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) </= 2.5x Upper Limit of Normal (ULN); c) International Normalized Ratio (INR) </= 2; factor 10A drawn if patient on anticoagulant Eliquis
  8. Adequate renal function: serum creatinine </=1.5x ULN
  9. Fasting serum cholesterol </= 300 mg/dL OR </= 7.75 mmol/L AND fasting triglycerides </= 2.5x 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;
  10. Signed informed consent obtained prior to any screening procedures.

Exclusion Criteria:

  1. Patients with grade 2-3 endometrioid, uterine serous, clear cell, mucinous, squamous, transitional cell, sarcomas, or carcinosarcoma histology
  2. Evidence of extrauterine spread of disease on imaging or during surgical evaluation.
  3. Patients who have prior therapy with everolimus or any other mTOR inhibitor.
  4. 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;
  5. Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus);
  6. Known intolerance or hypersensitivity to progesterone or its excipients
  7. 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 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.
  8. Uncontrolled diabetes mellitus as defined by 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;
  9. 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 O2 saturation 88% or less at rest on room air), e. active, bleeding diathesis;
  10. Chronic treatment with corticosteroids or other immunosuppressive agents. Topical or inhaled corticosteroids are allowed
  11. Patients who have a known history of human immunodeficiency virus (HIV) seropositivity
  12. 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-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines
  13. Other malignancies within the past 3 years except for basal or squamous cell carcinoma of the skin
  14. Active (acute or chronic) or uncontrolled severe infections (not responding to antibiotics), including acute pelvic inflammatory disease
  15. Congenital or acquired uterine anomaly which distorts the uterine cavity
  16. Genital actinomycosis
  17. 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
  18. Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing.
  19. Women who are pregnant or nursing (lactating) women
  20. 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.

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 ClinicalTrials.gov identifier (NCT number): NCT02397083


Contacts
Contact: Shannon Westin, MD 713-794-4314

Locations
United States, Texas
Memorial City Recruiting
Houston, Texas, United States, 77024
Lyndon B. Johnson General Hospital (LBJ) Recruiting
Houston, Texas, United States, 77026
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
The Woman's Hospital of Texas Recruiting
Houston, Texas, United States, 77054
Sponsors and Collaborators
M.D. Anderson Cancer Center
Novartis
Investigators
Principal Investigator: Shannon Westin, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT02397083     History of Changes
Other Study ID Numbers: 2014-0944
NCI-2015-00919 ( Other Identifier: NCI CTRP )
First Posted: March 24, 2015    Key Record Dates
Last Update Posted: July 16, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Endometrial Cancer
Everolimus
Afinitor
Zortress
RAD001
Endometrial hyperplasia
Intrauterine device
IUD
Levonorgestrel intrauterine device
LIUD
Mirena
Questionnaires
Survey
Quality of life
QOL

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Everolimus
Sirolimus
Uterine Diseases
Genital Diseases, Female
Levonorgestrel
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Contraceptives, Oral, Synthetic
Contraceptives, Oral