Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC

NCT03463252 | Recruiting Phase 2

• 1 other identifier: ZHENG Ying
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 1

Brief Summary

Primary end points: This clinical trial is aimed to analyze the effectiveness of Levonorgestrel-Releasing Intrauterine System (LNG-IUS, Mirena®) in the fertility-sparing treatment of atypical endometrial hyperplasia and early endometrial carcinoma, including pathology response and pregnancy outcome. Second end points: To analyze the appearances of side-effects.

Conditions

Endometrial Cancer; Atypical Endometrial Hyperplasia

Outcome Measures

Primary Outcomes (3)

• Pathologic Response

  Pathologic response to medicine treatment is categorized as complete response (CR), partial response (PR), no change (NC), and progressive disease (PD). CR is defined as the absence of any hyperplastic or cancerous lesion. PR is defined as the residual lesion with degeneration and atrophy of endometrial glands. NC is defined as residual lesion without degeneration or atrophy of endometrial glands. PD is defined as the appearance of endometrial cancer for EAH and grade 2 (G2) or 3 for EC.

  6-12 months

• Pregnancy Rate

  The percentage of successful pregnancies in the CR patients.

  7-144 months

• Live Birth Rate

  The percentage of successfully alive baby delivery in the pregnant patients.

  16-144 months

Secondary Outcomes (1)

• Side-Affects Rate

  1-144 months

Study Arms (9)

MPA for EC without progesterone contraindication

ACTIVE COMPARATOR

The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles.

Drug: Progesterone

MPA+Mirena® for EC without contraindication

EXPERIMENTAL

The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles.

Drug: Progesterone; Device: Mirena®

Mirena® for EC without contraindication

EXPERIMENTAL

The enrolled patient (endometrial cancer without contraindication of oral high dose progesterone) is allocated to one of three groups, MPA only, MPA+LNG-IUS, LNG-IUS only, by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles.

Device: Mirena®

GnRH agonist+Mirena® for EC with contraindication

ACTIVE COMPARATOR

The enrolled patient (endometrial cancer with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles.

Device: Mirena®; Drug: GnRH agonist

Mirena® for EC with contraindication

EXPERIMENTAL

The enrolled patient (endometrial cancer with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if endometrial cancer is still present after 3 cycles.

Device: Mirena®

Mirena® for EAH without progesterone contraindication

ACTIVE COMPARATOR

The enrolled patient (atypical endometrial hyperplasia without contraindication of oral high dose progesterone) is allocated to either MPA or LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles.

Device: Mirena®

MPA for EAH without progesterone contraindication

EXPERIMENTAL

The enrolled patient (atypical endometrial hyperplasia without contraindication of oral high dose progesterone) is allocated to either MPA or LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles.

Drug: Progesterone

Mirena® for EAH with progesterone contraindication

ACTIVE COMPARATOR

The enrolled patient (atypical endometrial hyperplasia with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles.

Device: Mirena®

GnRH-a+Mirena® for EAH with progesterone contraindication

EXPERIMENTAL

The enrolled patient (atypical endometrial hyperplasia with contraindication of oral high dose progesterone) is allocated to either GnRH-a+ LNG-IUS or only LNG-IUS by randomization. Continuous treatment for 3 months is one cycle. Hysteroscopic evaluation and biopsy will procedure every cycle. Patients with partial response or in stable condition, after 2 cycles, will receive continuous treatment for one more cycle again. Patients with complete response after 2 or 3 cycles are encouraged to pregnancy. The consideration of giving up fertility-sparing treatment is recommended: 1) if patient have documented progression on the biopsies; 2) if EAH is still present after 3 cycles.

Device: Mirena®; Drug: GnRH agonist

Interventions

Progesterone DRUG

MPA oral 250mg-500mg qd for 3 months per cycle

Also known as: medroxyprogesterone acetate (MPA)

MPA for EAH without progesterone contraindication; MPA for EC without progesterone contraindication; MPA+Mirena® for EC without contraindication

Mirena® DEVICE

levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle

Also known as: LNG-IUS

GnRH agonist+Mirena® for EC with contraindication; GnRH-a+Mirena® for EAH with progesterone contraindication; MPA+Mirena® for EC without contraindication; Mirena® for EAH with progesterone contraindication; Mirena® for EAH without progesterone contraindication; Mirena® for EC with contraindication; Mirena® for EC without contraindication

GnRH agonist DRUG

GnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle

Also known as: GnRH-a

GnRH agonist+Mirena® for EC with contraindication; GnRH-a+Mirena® for EAH with progesterone contraindication

Eligibility Criteria

• Age: Up to 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• ≤40 years of age:
• Having a strong desire for fertility preservation;
• Histological diagnosis is confirmed as well-differentiated (grade 1) endometrioid adenocarcinoma by the designated gynecological pathologists, and the progesterone receptors (PgRs) is positive in immunohistochemistry;
• Disease limited to the endometrium (stage 1A) on MRI;
• Serum CA125/199 level is within normal limit (Laparoscopic exploration to rule out ovarian tumor or another metastasis if necessary);
• Patients should have undergone counseling to learn fertility-preserving treatment is not standard of care for the treatment of EC, volunteered to participate in this study, signed the informed consent form, and agreed to participated in clinical follow-up.

You may not qualify if:

• Patients have allergies or contraindications (except for thromboembolic disease, liver dysfunction, hypertension, and diabetes) for the involved drugs;
• Patients have lynch syndrome (LS);
• Patients have contraindications for pregnancy;
• Patients have serious underlying disease, malignancies at other site(s), acute liver or kidney disease, acute liver or kidney diseases, acute or subacute genital tract infections and congenital or acquired abnormal uterine development (that may make intrauterine device placement impossible);
• Patients refuse to participate in clinical follow-up or sign the informed consent form.
• For Patients With Endometrial atypical hyperplasia：
• ≤ 40 years of age
• Having a strong desire for fertility preservation
• Histological diagnosis is confirmed as atypical endometrial hyperplasia (EAH) by the designated gynecological pathologists
• Having volunteered to participate in this study, signed the informed consent form, and agreed to participate in clinical follow-up
• Patients have allergies or contraindications (except for thromboembolic disease, liver dysfunction, hypertension, and diabetes) for the involved drugs
• Patients have contraindications for pregnancy
• Patients have serious underlying disease, malignancies at other site(s), acute liver or kidney disease, acute or subacute genital tract infections, and congenital or acquired abnormal uterine development (that may make intrauterine device placement impossible)
• Patients refuse to participate in clinical follow-up or sign the informed consent form.

Sponsors & Collaborators

• West China Second University Hospital: lead

Study Sites (1)

West China Second University Hospital

Chengdu, Sichuan, 610000, China

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Endometrial Neoplasms; Endometrial Hyperplasia

Interventions

Progesterone; Medroxyprogesterone Acetate; Gonadotropin-Releasing Hormone; ricin A-GnRH conjugate

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones; Medroxyprogesterone; Hydroxyprogesterones; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Central Study Contacts

ZHENG Ying, Professor

CONTACT

+8613018256012; 935398163@qq.com

CHEN Si Jing, postgraduate

CONTACT

+86218380361314; Zhy_chd@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor/Associate Director/Supervisor of Master Student

Study Record Dates

• First Submitted: March 4, 2018
• First Posted: March 13, 2018
• Study Start: April 1, 2018
• Primary Completion: December 30, 2025
• Study Completion (Estimated): December 30, 2030
• Last Updated: September 13, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)