Endometrial CancerPhase 2/3NCT03463252
Value of LNG-IUS as Fertility-preserving Treatment of EAH and EC
A Phase 2/3 study testing Progesterone, Mirena® and GnRH agonist in people with Endometrial Cancer and Atypical Endometrial Hyperplasia, run by West China Second University Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 40 years, women only
- Conditions the study is for
- Endometrial Cancer, Atypical Endometrial Hyperplasia
- What is being tested?
- Progesterone, Mirena® and GnRH agonist
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2018to 30 Dec 2030
- Phase
- Phase 2/3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 40 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- ≤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.
Show all 10Show fewer
- ≤ 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
Who cannot join
- 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：
Show all 10Show fewer
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
West China Second University Hospital
Chengdu, Sichuan, 610000
Zheng Ying, professor, +8613018256012, 935398163@qq.com
About this study
Official title: Value of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Fertility-preserving Treatment of Atypical Endometrial Hyperplasia and Early Endometrial Carcinoma
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.
- Being tested
- Progesterone, Mirena®, GnRH agonist
- Medical subject headings
- Endometrial Neoplasms, Endometrial Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProgesteroneDrug
Also called medroxyprogesterone acetate (MPA)
MPA oral 250mg-500mg qd for 3 months per cycle
Mirena®Device
Also called LNG-IUS
levonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle
GnRH agonistDrug
Also called GnRH-a
GnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Device: Mirena®; Drug: GnRH agonist |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6-12 months
Pregnancy Rate
The percentage of successful pregnancies in the CR patients.
Measured: 7-144 months
Live Birth Rate
The percentage of successfully alive baby delivery in the pregnant patients.
Measured: 16-144 months
Secondary outcomes (1)
Side-Affects Rate
The appearances of side-effects include weight gain, irregular vaginal bleeding, breast pain, appetite changes, nausea, vomiting, rash, jaundice, thromboembolism, hypertension, liver dysfunction, kidney dysfunction, glucose intolerance, and diabetes.
Measured: 1-144 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2018
- Study start1 Apr 2018
- Primary completion30 Dec 2025 (estimated)
- Study completion30 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Endometrial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 224 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West China Second University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zheng Ying, West China Second University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03463252
- Sponsor's protocol ID
- ZHENG Ying
- Status last verified
- Sep 2021
- First submitted
- 4 Mar 2018
- Last updated
- 13 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, Nakanishi T, Sasaki H, Saji F, Iwasaka T, Hatae M, Kodama S, Saito T, Terakawa N, Yaegashi N, Hiura M, Sakamoto A, Tsuda H, Fukunaga M, Kamura T. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007 Jul 1;25(19):2798-803. doi: 10.1200/JCO.2006.08.8344.
PubMed 17602085Rodolakis A, Biliatis I, Morice P, Reed N, Mangler M, Kesic V, Denschlag D. European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients. Int J Gynecol Cancer. 2015 Sep;25(7):1258-65. doi: 10.1097/IGC.0000000000000493.
PubMed 26186070Minig L, Franchi D, Boveri S, Casadio C, Bocciolone L, Sideri M. Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women. Ann Oncol. 2011 Mar;22(3):643-649. doi: 10.1093/annonc/mdq463. Epub 2010 Sep 28.
PubMed 20876910KELLEY RM, BAKER WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. doi: 10.1056/NEJM196102022640503. No abstract available.
PubMed 13752346Zhang Q, Qi G, Kanis MJ, Dong R, Cui B, Yang X, Kong B. Comparison among fertility-sparing therapies for well differentiated early-stage endometrial carcinoma and complex atypical hyperplasia. Oncotarget. 2017 May 3;8(34):57642-57653. doi: 10.18632/oncotarget.17588. eCollection 2017 Aug 22.
PubMed 28915701Wildemeersch D, Andrade A, Goldstuck N. Femilis((R)) 60 Levonorgestrel-Releasing Intrauterine System-A Review of 10 Years of Clinical Experience. Clin Med Insights Reprod Health. 2016 Aug 9;10:19-27. doi: 10.4137/CMRH.S40087. eCollection 2016.
PubMed 27547046Karimi-Zarchi M, Dehghani-Firoozabadi R, Tabatabaie A, Dehghani-Firoozabadi Z, Teimoori S, Chiti Z, Miratashi-Yazdi A, Dehghani A. A comparison of the effect of levonorgestrel IUD with oral medroxyprogesterone acetate on abnormal uterine bleeding with simple endometrial hyperplasia and fertility preservation. Clin Exp Obstet Gynecol. 2013;40(3):421-4.
PubMed 24283179Gallos ID, Shehmar M, Thangaratinam S, Papapostolou TK, Coomarasamy A, Gupta JK. Oral progestogens vs levonorgestrel-releasing intrauterine system for endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2010 Dec;203(6):547.e1-10. doi: 10.1016/j.ajog.2010.07.037.
PubMed 20934679Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.
PubMed 24286192Kim MK, Seong SJ, Kim JW, Jeon S, Choi HS, Lee IH, Lee JH, Ju W, Song ES, Park H, Ryu HS, Lee C, Kang SB. Management of Endometrial Hyperplasia With a Levonorgestrel-Releasing Intrauterine System: A Korean Gynecologic-Oncology Group Study. Int J Gynecol Cancer. 2016 May;26(4):711-5. doi: 10.1097/IGC.0000000000000669.
PubMed 26905333Practice Bulletin No. 149: Endometrial cancer. Obstet Gynecol. 2015 Apr;125(4):1006-1026. doi: 10.1097/01.AOG.0000462977.61229.de. No abstract available.
PubMed 25798986Colombo N, Creutzberg C, Amant F, Bosse T, Gonzalez-Martin A, Ledermann J, Marth C, Nout R, Querleu D, Mirza MR, Sessa C; ESMO-ESGO-ESTRO Endometrial Consensus Conference Working Group. ESMO-ESGO-ESTRO consensus conference on endometrial cancer: Diagnosis, treatment and follow-up. Radiother Oncol. 2015 Dec;117(3):559-81. doi: 10.1016/j.radonc.2015.11.013. Epub 2015 Dec 9.
PubMed 26683800Lee SW, Lee TS, Hong DG, No JH, Park DC, Bae JM, Seong SJ, Shin SJ, Ju W, Lee KH, Lee YK, Cho H, Lee C, Paek J, Kim HJ, Lee JW, Kim JW, Bae DS. Practice guidelines for management of uterine corpus cancer in Korea: a Korean Society of Gynecologic Oncology Consensus Statement. J Gynecol Oncol. 2017 Jan;28(1):e12. doi: 10.3802/jgo.2017.28.e12. Epub 2016 Oct 27.
PubMed 27894165Denny L, Quinn M. FIGO Cancer Report 2015. Int J Gynaecol Obstet. 2015 Oct;131 Suppl 2:S75. doi: 10.1016/j.ijgo.2015.06.024. No abstract available.
PubMed 26433677The American College of Obstetricians and Gynecologists Committee Opinion no. 631. Endometrial intraepithelial neoplasia. Obstet Gynecol. 2015 May;125(5):1272-1278. doi: 10.1097/01.AOG.0000465189.50026.20.
PubMed 25932867
Study at a glance
From the registry record, last updated by the sponsor on 13 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Value of Levonorgestrel-Releasing Intrauterine System (LNG-IUS) in the Fertility-preserving Treatment of Atypical Endometrial Hyperplasia and Early Endometrial Carcinoma
- ClinicalTrials.gov ID
- NCT03463252
- Acronym / sponsor ID
- ZHENG Ying
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 224 participants (estimated)
- Lead sponsor
- West China Second University HospitalUniversity, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 30 Dec 2025 (estimated)
- Study completion
- 30 Dec 2030 (estimated)
- First posted
- 13 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 9
| Arm | Type | Receives |
|---|---|---|
| MPA for EC without progesterone contraindication | Active comparator | Drug: ProgesteroneThe 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. |
| MPA+Mirena® for EC without contraindication | Experimental | Drug: Progesterone, Device: Mirena®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. |
| Mirena® for EC without contraindication | Experimental | Device: Mirena®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. |
| GnRH agonist+Mirena® for EC with contraindication | Active comparator | Device: Mirena®, Drug: GnRH agonistThe 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. |
| Mirena® for EC with contraindication | Experimental | Device: Mirena®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. |
| Mirena® for EAH without progesterone contraindication | Active comparator | Device: Mirena®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. |
| MPA for EAH without progesterone contraindication | Experimental | Drug: ProgesteroneThe 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. |
| Mirena® for EAH with progesterone contraindication | Active comparator | Device: Mirena®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. |
| GnRH-a+Mirena® for EAH with progesterone contraindication | Experimental | Device: Mirena®, Drug: GnRH agonistThe 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. |
Who may qualify
- Ages
- Up to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- ≤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);
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ProgesteroneAlso: medroxyprogesterone acetate (MPA)MPA oral 250mg-500mg qd for 3 months per cycle | Drug | MPA for EAH without progesterone contraindication, MPA for EC without progesterone contraindication, MPA+Mirena® for EC without contraindication |
| Mirena®Also: LNG-IUSlevonorgestrel intrauterine sustained release system (LNG-IUS) placed in uterus for 3 months per cycle | Device | 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 agonistAlso: GnRH-aGnRH-a intramuscular injection 3.75mg once a month for 3 months per cycle | Drug | GnRH agonist+Mirena® for EC with contraindication, GnRH-a+Mirena® for EAH with progesterone contraindication |
Primary outcome
Pathologic Response
Time frame: 6-12 months
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.
Pregnancy Rate
Time frame: 7-144 months
The percentage of successful pregnancies in the CR patients.
Live Birth Rate
Time frame: 16-144 months
The percentage of successfully alive baby delivery in the pregnant patients.
1 secondary outcome
Side-Affects Rate
Time frame: 1-144 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Sep 2021.
- Background: PubMed 17602085Ushijima K, Yahata H, Yoshikawa H, Konishi I, Yasugi T, Saito T, Nakanishi T, Sasaki H, Saji F, Iwasaka T, Hatae M, Kodama S, Saito T, Terakawa N, Yaegashi N, Hiura M, Sakamoto A, Tsuda H, Fukunaga M, Kamura T. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol. 2007 Jul 1;25(19):2798-803. doi: 10.1200/JCO.2006.08.8344.
- Background: PubMed 26186070Rodolakis A, Biliatis I, Morice P, Reed N, Mangler M, Kesic V, Denschlag D. European Society of Gynecological Oncology Task Force for Fertility Preservation: Clinical Recommendations for Fertility-Sparing Management in Young Endometrial Cancer Patients. Int J Gynecol Cancer. 2015 Sep;25(7):1258-65. doi: 10.1097/IGC.0000000000000493.
- Background: PubMed 20876910Minig L, Franchi D, Boveri S, Casadio C, Bocciolone L, Sideri M. Progestin intrauterine device and GnRH analogue for uterus-sparing treatment of endometrial precancers and well-differentiated early endometrial carcinoma in young women. Ann Oncol. 2011 Mar;22(3):643-649. doi: 10.1093/annonc/mdq463. Epub 2010 Sep 28.
- Background: PubMed 13752346KELLEY RM, BAKER WH. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med. 1961 Feb 2;264:216-22. doi: 10.1056/NEJM196102022640503. No abstract available.
- Background: PubMed 28915701Zhang Q, Qi G, Kanis MJ, Dong R, Cui B, Yang X, Kong B. Comparison among fertility-sparing therapies for well differentiated early-stage endometrial carcinoma and complex atypical hyperplasia. Oncotarget. 2017 May 3;8(34):57642-57653. doi: 10.18632/oncotarget.17588. eCollection 2017 Aug 22.
- Background: PubMed 27547046Wildemeersch D, Andrade A, Goldstuck N. Femilis((R)) 60 Levonorgestrel-Releasing Intrauterine System-A Review of 10 Years of Clinical Experience. Clin Med Insights Reprod Health. 2016 Aug 9;10:19-27. doi: 10.4137/CMRH.S40087. eCollection 2016.
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- Background: PubMed 24286192Orbo A, Vereide A, Arnes M, Pettersen I, Straume B. Levonorgestrel-impregnated intrauterine device as treatment for endometrial hyperplasia: a national multicentre randomised trial. BJOG. 2014 Mar;121(4):477-86. doi: 10.1111/1471-0528.12499. Epub 2013 Nov 28.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Progesterone, Mirena® and GnRH agonist in people with Endometrial Cancer and Atypical Endometrial Hyperplasia, run by West China Second University Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact ZHENG Ying, Professor (+8613018256012, 935398163@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Response (time frame: 6-12 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03463252, which also lists 22 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2021.