Adjuvant Therapy for Endometrial Cancer
(RAINBO Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Overseen byMelanie E Powell, Md PhD
Age: 18+
Sex: Female
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Leiden University Medical Center
Must not be taking: PARP inhibitors, PD(L)1 inhibitors, CYP3A inhibitors, CYP3A inducers
Disqualifiers: Other malignancy, Prior pelvic radiation, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial tests new treatments for endometrial cancer based on the cancer's genetic makeup. Patients are grouped by their cancer type and given tailored treatments combining radiation, chemotherapy, and targeted drugs. The aim is to find the most effective and least harmful treatments for each specific type of endometrial cancer. Dostarlimab has shown promising results in treating endometrial cancer, with a trial curing 100% of CRC patients without severe adverse events.
Will I have to stop taking my current medications?
The trial requires a washout period (time without taking certain medications) for specific drugs. If you are taking strong or moderate CYP3A inhibitors or inducers, you will need to stop them 2 to 5 weeks before starting the trial medication. Please consult with the trial team for guidance on your specific medications.
What data supports the effectiveness of the drug combination including medroxyprogesterone acetate for endometrial cancer?
Research shows that medroxyprogesterone acetate, a component of the treatment, has been effective in treating advanced endometrial cancer, with some patients experiencing partial responses and prolonged survival. Additionally, combination therapies including medroxyprogesterone acetate have shown promising results in achieving complete remission in some cases of recurrent endometrial cancer.
12345Is the treatment generally safe for humans?
Medroxyprogesterone acetate (Depo-Provera) has been shown to be safe in various studies, with minor side effects like menstrual irregularities and amenorrhea (absence of menstruation) reported. It is effective and safe for conditions like endometrial hyperplasia and has been used in contraceptive formulations with a good safety profile.
16789How does the drug used in adjuvant therapy for endometrial cancer differ from other treatments?
The adjuvant therapy for endometrial cancer may involve the use of medroxyprogesterone acetate (MPA), which is a hormone therapy that can be taken orally and is used to treat hormone-dependent tumors. This treatment is unique because it offers an alternative to conventional treatments, especially for maintenance therapy, and is easy to administer over long periods.
1241011Eligibility Criteria
This trial is for patients with endometrial cancer, categorized by their cancer's molecular profile. They must have a WHO performance status of 0-2, weigh over 30 kg, and have no distant metastases or major surgeries within the last 28 days. Patients should not have had prior treatments that conflict with the trial drugs and must be able to follow up for treatment.Inclusion Criteria
I have had my uterus and both ovaries removed with no visible disease left.
I can take care of myself but may not be able to do heavy physical work.
Patients must be accessible for treatment and follow-up
+5 more
Exclusion Criteria
I have had another type of cancer in the last 5 years.
I have had radiation therapy to my pelvic area before.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive adjuvant chemoradiation followed by specific therapies based on molecular profile: olaparib, durvalumab, progestogens, or no adjuvant therapy
1-2 years
Follow-up
Participants are monitored for recurrence-free survival and other outcomes
3-5 years
Participant Groups
The RAINBO program includes four trials testing new adjuvant therapies in endometrial cancer based on molecular profiles: p53abn-RED for p53 abnormal cancers; MMRd-GREEN for mismatch repair deficient; NSMP-ORANGE when there's no specific profile; POLEmut-BLUE for POLE mutant cancers.
8Treatment groups
Experimental Treatment
Active Control
Group I: p53abn-RED trial: experimentalExperimental Treatment4 Interventions
Adjuvant radiotherapy and chemotherapy followed by olaparib (lynparza), 300 mg twice daily, for one year
Group II: POLEmut-BLUE trial: main cohortExperimental Treatment1 Intervention
No adjuvant therapy in women with:
* stage IA (not confined to polyp), grade 3, pN0, with or without LVSI
* stage IB, grade 1 or 2, pNx/N0, with or without LVSI
* stage IB, grade 3, pN0, without substantial LVSI
* stage II (microscopic), grade 1 or 2, pN0, without substantial LVSI
Group III: POLEmut-BLUE trial: exploratory cohortExperimental Treatment3 Interventions
No adjuvant therapy or vaginal brachytherapy or pelvic external beam radiotherapy in women with:
* stage IA grade 3 - stage III not included in main cohort of the POLEmut-BLUE trial
* Multiple molecular classifiers Stage IA (not confined to polyp), grade 3 - Stage III
Group IV: NSMP-ORANGE trial: experimentalExperimental Treatment4 Interventions
Adjuvant radiotherapy followed by oral progestagens (medroxyprogesterone acetate or megestrol acetate) for two years
Group V: MMRd-GREEN trial: experimentalExperimental Treatment3 Interventions
Adjuvant radiotherapy combined with and followed by durvalumab, 1500 mg intravenous once every 4 weeks for in total 1 year (13 cycles)
Group VI: MMRd-GREEN trial: controlActive Control3 Interventions
Adjuvant pelvic external beam radiotherapy +/- chemotherapy
Group VII: NSMP-ORANGE trial: controlActive Control3 Interventions
Adjuvant radiotherapy and chemotherapy
Group VIII: p53abn-RED trial: controlActive Control3 Interventions
Adjuvant radiotherapy and chemotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
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Who Is Running the Clinical Trial?
Leiden University Medical CenterLead Sponsor
Dutch Gynaecological Oncology GroupCollaborator
University College London (sponsor NSMP-ORANGE trial)Collaborator
AstraZenecaIndustry Sponsor
Canadian Institutes of Health Research (CIHR)Collaborator
National Cancer Institute, FranceCollaborator
Cancer Research UK & UCL Cancer Trials CentreCollaborator
Leiden University Medical center (sponsor MMRd-GREEN trial)Collaborator
Institute Gustave Roussy (sponsor p53abn-RED trial)Collaborator
Comprehensive Cancer Centre The NetherlandsCollaborator
References
[Oral high doses of medroxyprogesterone acetate (MPA) in the treatment of advanced phases of breast and endometrial cancer]. [2013]The results of a pilot study on the use of oral medroxyprogesterone acetate (Provera-Upjohn) at high dose in a series of 50 consecutive women with advanced breast (30 cases) and endometrial carcinoma (20 cases) are reported. Patients with progressive disease, non liable to further conventional treatments, received MPA (500 mg/day orally) for 90 days. The evaluation of results have shown only partial responses: in 9/30 (30%) of women with disseminated breast carcinoma (median duration of response 10 months, median survival 15 months), and in 6/20 (30%) of patients with advanced endometrial carcinoma (median duration of response 15 months, median survival not reached at 28 months of follow-up). Even if with a lower response rate, as compared to the results obtained with parenteral formulation, the oral MPA maintains its therapeutic effectiveness in these hormonodependent tumors: easy to handle during the long term treatments, oral MPA could be a useful alternative also for maintenance therapy.
Combination chemotherapy for advanced endometrial adenocarcinoma. [2019]Two patients with measurable recurrent endometrial adenocarcinoma achieved complete remission proven by second-look operation. Both patients were treated with a combination of melphalan, 5-fluorouracil and medroxyprogesterone acetate.
Genome-wide CRISPR screening reveals ADCK3 as a key regulator in sensitizing endometrial carcinoma cells to MPA therapy. [2023]The effectiveness of conservative treatment of endometrial carcinoma (EC) with oral progesterone therapy, such as medroxyprogesterone acetate (MPA), can be blunted due to primary or acquired resistance, but the underlying mechanisms remain incompletely defined.
Case report: prolonged durable clinical benefit and low toxicity from combination endocrine therapy in a patient with recurrent endometrial carcinoma. [2023]Endometrial carcinoma is the most common gynecologic cancer, with increasing incidence and mortality. Combination endocrine therapy comprised of tamoxifen and progestational agents has demonstrated promising results in treating recurrent disease. This case report describes the prolonged clinical benefit of treatment with tamoxifen and megestrol acetate in a woman with recurrent, metastatic endometrial endometrioid carcinoma positive for estrogen (ER) and progesterone receptors (PR).
Tamoxifen, megestrol acetate, and beta interferon in endometrial cancer. [2020]22 patients with endometrial cancer were studied. Twelve (54.5%) between 45 and 66 years were treated for six days before surgery with 160 mg per os of Megestrol acetate administered twice daily plus Beta interferon 3,000,000 IU- on alternate days for a week, plus Tamoxifen--two cp of 10 mg daily for six days. Before and after surgery and associated medical therapies the steroid receptor values (ER and PgR) were checked. After treatment an average increase was observed of the ER (19 fmol/mg) and PgR (17 fmol/mg). Of the twelve patients one died of a stroke during the study (8.33%); five (41.67%) showed complete remission (CR); four (33.34%) a partial remission (PR) and two (16.67%) were not responders (NR).
Current options for injectable contraception in the United States. [2013]Two injectable forms of hormonal contraception, depot medroxyprogesterone acetate (DMPA, Depo-Provera) and medroxyprogesterone acetate/estradiol cypionate (MPA/E(2)C, Lunelle), are now available to American women. Both formulations have demonstrated high degrees of efficacy, safety, and ease of use in international and U.S. trials. Data on DMPA have shown a number of noncontraceptive and therapeutic benefits, the most prominent of which is an 80% reduction in the risk of endometrial cancer. Although such benefits are less documented for MPA/E(2)C, they are expected to be similar to those seen with DMPA and oral contraceptives. Minor side effects of both formulations include menstrual irregularities in the early months of treatment and amenorrhea with DMPA. Patient counseling about the potential for these side effects, as well as possible risks, is important to long-term successful use of these contraceptive methods.
Clinical trial to evaluate pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after subcutaneous administration of Depo-Provera. [2021]To evaluate the pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate after a single subcutaneous injection in the abdomen of 150 or 300 mg Depo-Provera and compare results to two injections of Depo-SubQ Provera 104 given 3 months apart.
A randomized crossover study to evaluate local tolerability following subcutaneous administration of a new depot medroxyprogesterone acetate contraceptive formulation. [2023]This study aimed to evaluate and compare local tolerability of investigational drug TV-46046 and reference drug Depo-subQ Provera 104, both containing medroxyprogesterone acetate (MPA) as an active ingredient.
Depo-Provera Versus Norethisterone Acetate in Management of Endometrial Hyperplasia Without Atypia. [2018]The objective of this study was to assess effectiveness and safety of Depo-Provera (medroxyprogesterone acetate) in treatment of endometrial hyperplasia (EH) and to compare it with norethisterone acetate (NETA) as an oral progestogen treatment. One hundred forty six women aged 35 to 50 years with abnormal uterine bleeding and diagnosed as having EH were randomized to receive either Depo-Provera, one injection every 3 months for 6 months (2 doses), or oral cyclic NETA, 15 mg daily for 14 days per cycle for 6 months. Primary outcome measure was regression of EH. Secondary outcome variables were side effects of treatment, persistence/progression of EH during follow-up period. After 6 months of treatment, Depo-Provera was more successful in achieving regression of nonatypical EH than NETA (67 [91.8%] of 73 women vs 49 [67.1%] of 73, respectively), and the difference between the 2 groups was statistically significant (relative risk: 1.37; 95% confidence interval: 1.15-1.63, P = .048*). Adverse effects were relatively common with moderate differences between the 2 groups. This is the first randomized study comparing Depo-Provera with an oral progestogen as a treatment for EH. Depo-Provera is an effective and safe treatment for EH without atypia.
Stage I endometrial carcinoma: the role of neoadjuvant progesterone therapy. [2019]A prospective study was devised in 1980 to assess the effect on survival of neoadjuvant Provera as part of the primary treatment of endometrial carcinoma in conjunction with surgery and radiotherapy. Between June 1980 and June 1985, 218 patients with Stage I adenocarcinoma of the corpus uteri were allocated on the basis of hospital of presentation to receive either neoadjuvant treatment with medroxyprogesterone acetate (MPA) 100 mg t.i.d. p.o. from diagnosis for 90 days, or no adjuvant treatment (the control group). The minimum follow-up was 5 years. There was no significant difference between the overall actuarial survival in the treatment group (123 cases) and that in the control group (95 cases). This was 83.7% and 69.2% at 5 and 10 years respectively in the treatment group and 78.9% and 70.7% in the control group (P > 0.1).
Adjuvant endocrine treatment with medroxyprogesterone acetate or tamoxifen in stage I and II endometrial cancer--a multicentre, open, controlled, prospectively randomised trial. [2019]Endometrial cancer is a hormone-dependent disease and therefore an adjuvant hormonal therapy might improve the outcome in the early stages of the disease. Between 1983 and 1989, we conducted a randomised trial of 388 patients who received either medroxyprogesterone acetate (MPA) (n=133) or tamoxifen (n=121) orally for 2 years, or were observed only (n=134) after surgical therapy. The aim was to evaluate whether an adjuvant treatment can improve disease-free and overall survival rates. After a median follow-up period of 56 months (range 3-199 months), we observed no differences in the disease-free and overall survival rates for the tamoxifen group compared with the control or the MPA group. Side-effects were more frequent and severe in the MPA-group than in the tamoxifen group. In patients with early endometrial cancer, adjuvant endocrine treatment did not significantly improve the outcome. However, tamoxifen did have some beneficial effects on coexisting morbidity.