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

West China Second University Hospital

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Endometrial Cancer; Atypical Endometrial Hyperplasia

Treatments: Device: Mirena®; Drug: Progesterone; Drug: GnRH agonist

Study type: Interventional

Funder types: Other

Identifiers

NCT03463252

ZHENG Ying

Details and patient eligibility

About

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.

Enrollment: 224 estimated patients

Sex: Female

Ages: Under 40 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

For Patients With Endometrial Cancer：

Inclusion Criteria:

• ≤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.

Exclusion Criteria:

• 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：

Inclusion Criteria:

• ≤ 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

Exclusion Criteria:

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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224 participants in 9 patient groups

MPA for EC without progesterone contraindication

Active Comparator group

Description:

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.

Treatment:

Drug: Progesterone

MPA+Mirena® for EC without contraindication

Experimental group

Description:

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.

Treatment:

Drug: Progesterone

Device: Mirena®

Mirena® for EC without contraindication

Experimental group

Description:

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.

Treatment:

Device: Mirena®

GnRH agonist+Mirena® for EC with contraindication

Active Comparator group

Description:

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.

Treatment:

Drug: GnRH agonist

Device: Mirena®

Mirena® for EC with contraindication

Experimental group

Description:

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.

Treatment:

Device: Mirena®

Mirena® for EAH without progesterone contraindication

Active Comparator group

Description:

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.

Treatment:

Device: Mirena®

MPA for EAH without progesterone contraindication

Experimental group

Description:

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.

Treatment:

Drug: Progesterone

Mirena® for EAH with progesterone contraindication

Active Comparator group

Description:

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.

Treatment:

Device: Mirena®

GnRH-a+Mirena® for EAH with progesterone contraindication

Experimental group

Description:

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.

Treatment:

Drug: GnRH agonist

Device: Mirena®