AzTrials
AzTrials

Endometrial CancerPhase 2NCT04743999

Evaluation of Outcomes in Women Undergoing Multimodality Treatment for Advanced Stage Endometrial Carcinoma

A Phase 2 study testing Quality of life questionnaire in people with Endometrial Cancer, run by Henry Ford Health System at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Patients with FIGO stage III endometrial carcinoma often require multimodality adjuvant therapy to improve survival and recurrence rates; however, the optimal adjuvant therapy sequence is yet to be established. Several studies have tried to answer this question including RTOG 9708, PORTEC-3, and GOG 258. Read more about this study

Who is it for?
Ages 18 to 90 years, women onlyHealthy volunteers can take part
Conditions the study is for
Endometrial Cancer
What is being tested?
Quality of life questionnaire
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
27 Feb 2020to 27 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 to 90 years
  • Women only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • FIGO stage III uterine carcinoma
  • candidates for combined modality treatment (surgery, chemotherapy with carbo/Taxol, and radiation therapy)

Who cannot join

  • Patients who are not FIGO stage III
  • patients with carcinosarcoma histology
  • patients who are ineligible for combined modality treatment

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Henry Ford Cancer Institute

    Detroit, Michigan, 48202

Other trials in United States

About this study

Official title: Prospective Evaluation of Quality of Life and Treatment-related Side Effects of Women Undergoing Multimodality Treatment for Advanced Stage Endometrial Carcinoma

Patients with FIGO stage III endometrial carcinoma often require multimodality adjuvant therapy to improve survival and recurrence rates; however, the optimal adjuvant therapy sequence is yet to be established.

Several studies have tried to answer this question including RTOG 9708, PORTEC-3, and GOG 258. Collectively, these studies show that concurrent chemotherapy and radiation (chemoRT) with cisplatin followed by additional chemotherapy (CT) and CT alone are acceptable regimens. However, both strategies show that distant recurrence remains a problem when CT is delayed after RT, and local control is compromised without RT.

Read more

We wish to prospectively assess outcomes of women with advanced endometrial carcinoma who receive concurrent chemoRT with a carboplatin/paclitaxel-based regimen.

A total of 60 patients with FIGO stage III uterine carcinoma will be prospectively enrolled after undergoing surgical staging (currently accruing). CT will start approximately 4 weeks after surgery. Patients will receive 6 cycles of carboplatin (AUC 6) and paclitaxel (175 mg/m2).

RT will be given during CT cycles 1-3. External beam RT will be given via intensity-modulated RT in once-daily fractions of 1.8-2.0 Gy for a total dose of 44-45 Gy to the pelvis (vaginal cuff, pelvic LN, and para-aortic lymph nodes). If there is grossly visible nodal disease seen at the time of treatment planning, a boost to 54 Gy will be given to those areas. If the patient has cervical stromal invasion, we will recommend that she receive a brachytherapy boost.

Data will be collected on OS and PFS endpoints. Data will also be collected on provider- and patient-reported treatment toxicity. Patients will receive a series of questionnaires at baseline, 3, 6, 12, and 24 months after surgery. These are prospectively-validated questionnaires and include FACT-G, FACT-En, FACT/GOG-NTX, and FACT-C.

For statistical analyses, continuous and categorical variables will be analyzed. Kaplan-Meier survival estimates will be calculated for local control and survival end points. For each patient, disease characteristics and adjuvant treatment will be placed in a simple logistic regression model for predicting survival endpoints. A multivariate analysis will be performed for exploratory purposes. Hazard ratios and 95% confidence intervals will be reported. Tests will be considered significant at p < 0.05.

Read the detailed description

Purpose: To prospectively determine patients' quality of life (QOL) and treatment-related toxicity outcomes with adjuvant multimodality treatment (chemotherapy and radiation treatment) in women with advanced endometrial carcinoma after surgical staging.

Specific Aims:

  1. To prospectively determine QOL after adjuvant treatment using the prospectively-validated FACT questionnaires at baseline, 3, 6, 12, and 24 months after surgical staging
  2. To prospectively determine the rate of any grade 2 or higher treatment-related side effects: mainly bone marrow suppression, lymphedema, diarrhea, and others. Additionally, we will collect information about the rate of completion of planned adjuvant treatment (number of chemotherapy cycles, dose reduction or chemotherapy delay, radiation treatment interruption, etc.).
  3. To prospectively collect survival outcome endpoints after adjuvant treatment (recurrence-free, disease-specific and overall survival).

Introduction and Rationale: Endometrial cancer is the most common gynecologic malignancy in the United States and ranks second in gynecologic cancer mortality following only ovarian cancer. More than 84% of patients present with International Federation of Gynecology and Obstetrics (FIGO) stage I-II disease. By definition, patients with advanced-stage uterine carcinoma (FIGO stages III-IV) are those with extrauterine disease and are at significant risk of dying from uterine cancer. They constitute a very heterogeneous group of patients with varying risk factors yielding highly variable clinical outcomes. Within the same FIGO stage, patients with disease involving multiple extrauterine sites fare worse compared to patients with involvement of a single site (1).

Postoperatively, patients with advanced stage disease often require adjuvant therapy(s) to reduce the chance of tumor recurrence with the potential to improve survival. However, the optimal adjuvant therapy is yet to be established with several options available for adjuvant treatment.

Rationale for multimodality treatment with chemotherapy and radiation treatment (CMT):

Current treatment recommendations for advanced stage endometrial cancer consist of multiple approaches including chemotherapy alone, radiotherapy (RT) alone, or combined modality treatment (CMT) (2).

GOG 122 study, which was a phase III trial, randomized patient with advanced endometrial carcinoma to adjuvant chemotherapy alone versus whole abdomen RT (WART). Outcomes of this study showed that the chemotherapy arm had an improved 5-year progression-free survival (PFS) and overall survival (OS) compared to RT alone. However, this trial showed that if chemotherapy is given alone, that rate of local recurrence approaches 20% (3).

The safety of CMT with concurrent chemotherapy and RT (chemoRT) was explored in RTOG 9708, which was a phase II trial that evaluated outcomes in patients receiving concurrent chemoRT. All patients received adjuvant pelvic RT (45 Gy) concurrent with cisplatin followed by four additional cycles of cisplatin and paclitaxel. The 4-year OS and PFS for patients with stage III disease were 77% and 72%, respectively. Rates of grade 1 toxicity were found in 16% of patients, grade 2 in 41%, grade 3 in 16%, and grade 4 in 5%. This study demonstrated that concurrent chemoRT is safe with excellent local control (4).

More recent studies have sought to compare chemoRT to chemotherapy or radiation alone. PORTEC-3 was a phase III randomized trial comparing adjuvant RT alone to concurrent chemoRT. The RT dose was 48.6 Gy in 27 fractions and chemotherapy was concurrent cisplatin followed by an additional 4 cycles of carboplatin and paclitaxel. For women with stage III disease, the addition of chemotherapy to radiation treatment showed benefit in terms of improvement in FFS. An analysis of toxicity outcomes found that 60% of patients in the chemoRT arm experienced a grade 3 or greater adverse event compared to 12% in the RT alone arm (p<0.0001) (5).

GOG 258 study was recently published and was similar to PORTEC-3 except that it compared concurrent chemoRT to adjuvant chemotherapy alone. Patients were randomized to receive concurrent chemoRT (45 Gy in 25 fractions concurrent with cisplatin followed by 4 cycles of carboplatin and paclitaxel) or chemotherapy alone. The results of this study showed that chemoRT was associated with a lower 5-year incidence of vaginal and regional lymphatic recurrence. However, distant recurrence rates were higher in the chemoRT arm compared to chemotherapy alone (6).

The above studies helped to establish concurrent chemoRT with cisplatin followed by adjuvant carboplatin/paclitaxel as a valid adjuvant treatment approach for women with advanced endometrial carcinoma.

A retrospective review from Washington University included 51 women with stage III-IV endometrial carcinoma who received CMT with carboplatin/paclitaxel-based regimen concurrent with RT and assessed survival and toxicity outcomes. The chemotherapy regimen given was carboplatin/paclitaxel for 4-6 cycles and RT was 48-51.2 Gy. Patients also received a vaginal brachytherapy boost. They found that 48 patients (94%) completed chemotherapy and 16 patients (30%) required chemotherapy dose-reduction. Thirty-four patients experienced grade 3-4 toxicities, most of which were hematologic. Over 80% of patients required leukocyte growth factor injections. There were seven late grade 3-4 toxicities (4 GI, 2 GU, and 1 ongoing neuropathy). They found a median PFS of 42.8 months, median OS of 44.9 months, and 3-year OS of 80% (7). This study suggests that concurrent chemoRT using a carbotaxol-based regimen has favorable outcomes, a tolerable side effect profile, and the potential to reduce overall treatment duration.

Building off of the results of the above retrospective study as well as the aforementioned randomized trials, we wish to prospectively assess outcomes of women with advanced endometrial carcinoma who receive the same concurrent chemoRT with a carboplatin/paclitaxel-based regimen.

Being tested
Quality of life questionnaire
Medical subject headings
Endometrial Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Quality of life questionnaireOther

    We will evaluate patients' quality of life with a series of questionnaires at baseline, 3, 6, 12, and 24 months after surgical staging. These are prospectively validated questionnaires and include FACT-G (physical and functional well-being sections), FACT-En (additional concerns section), FACT/GOG-NTX-4 (additional concerns section), and FACT-C (items C3 and C5).These sections will be combined into one single form for ease of completion for the patients (a total of 36 items).

Study groups in NCT04743999
Study groupRoleWhat they receive
Quality of life evaluationExperimentalThis prospective arm will consist of evaluating quality of life outcomes in women in women with advanced endometrial cancer undergoing adjuvant concurrent chemotherapy with carbo/Taxol and radiation therapy. Assessments will occur following surgery (baseline), 3, 6, 12, and 24 months.
Receives: Other: Quality of life questionnaire

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Assessment of Physical and Functional Well-being as Assessed by the FACT-G Questionnaire

    The Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire is a prospectively validated form that assesses physical side effects of treatment (eg pain, nausea, fatigue) as well as treatment's functional impact (eg ability to work, enjoy hobbies). Scale: 0-4. 0: Not at all, 4: Very much

    Values reported as "0.00 (0.00)" are accurate in all outcome measures.

    Measured: Baseline, 3-month, 6-month, 12-month, 24-month

  2. Assessment of Severity of Various Treatment-related Side Effects as Assessed by the FACT-En Questionnaire

    The Functional Assessment of Cancer Therapy - Endometrial (FACT-EN) questionnaire is a prospectively-validated questionnaire that asks patients to rated the severity of various possible treatment side effects (eg GI pain, pelvic pain, shortness of breath) Scale: 0-4. 0: Not at all, 4: Very much

    Measured: Baseline, 3-month, 6-month, 12-month, 24-month

  3. Assessment of Severity of Neurotoxicity Side Effects as Assessed by the FACT/GOG-NTX-4 Scale

    The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity 4 Item Version (FACT/GOG-NTX-4) scale is a prospectively-validated questionnaire that assesses the severity of side effects related to neurotoxicity (paresthesia, pain in hands/feet) Scale: 0-4. 0: Not at all, 4: Very much

    Measured: Baseline, 3-month, 6-month, 12-month, 24-month

  4. Assessment of Severity of GI Side Effects as Assessed by the FACT-C Questionnaire

    The Functional Assessment of Cancer Therapy - Colorectal (FACT-C) scale is a prospectively-validated questionnaire that asses GI-related side effects (diarrhea, fecal incontinence) Scale: 0-4. 0: Not at all, 4: Very much

    Measured: Baseline, 3-month, 6-month, 12-month, 24-month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2021
  2. Study start27 Feb 2020
  3. Primary completion27 Jun 2023
  4. Study completion27 Jun 2023

Why it stopped: Low accrual

Resources

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
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04743999
Sponsor's protocol ID
13551
Status last verified
Mar 2024
First submitted
3 Feb 2021
Last updated
29 Mar 2024
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Elshaikh MA, Yashar CM, Wolfson AH, Cardenes HR, Erickson B, Jhingran A, Jolly S, Kidd E, Lee LJ, Mayr NA, Moore D, Rao GG, Small W Jr, Varia MA, Wahl AO, Yuh W, Gaffney DK; Expert Panel on Radiation Oncology-Gynecology:. ACR appropriateness Criteria(R) advanced stage endometrial cancer. Am J Clin Oncol. 2014 Aug;37(4):391-6. doi: 10.1097/COC.0000000000000098.

    PubMed 24977691
  • NCCN Guidelines Version 3.2019 Endometrial Carcinoma

  • Randall ME, Filiaci VL, Muss H, Spirtos NM, Mannel RS, Fowler J, Thigpen JT, Benda JA; Gynecologic Oncology Group Study. Randomized phase III trial of whole-abdominal irradiation versus doxorubicin and cisplatin chemotherapy in advanced endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol. 2006 Jan 1;24(1):36-44. doi: 10.1200/JCO.2004.00.7617. Epub 2005 Dec 5.

    PubMed 16330675
  • Greven K, Winter K, Underhill K, Fontenesci J, Cooper J, Burke T. Final analysis of RTOG 9708: adjuvant postoperative irradiation combined with cisplatin/paclitaxel chemotherapy following surgery for patients with high-risk endometrial cancer. Gynecol Oncol. 2006 Oct;103(1):155-9. doi: 10.1016/j.ygyno.2006.02.007. Epub 2006 Mar 20.

    PubMed 16545437
  • de Boer SM, Powell ME, Mileshkin L, Katsaros D, Bessette P, Haie-Meder C, Ottevanger PB, Ledermann JA, Khaw P, Colombo A, Fyles A, Baron MH, Jurgenliemk-Schulz IM, Kitchener HC, Nijman HW, Wilson G, Brooks S, Carinelli S, Provencher D, Hanzen C, Lutgens LCHW, Smit VTHBM, Singh N, Do V, D'Amico R, Nout RA, Feeney A, Verhoeven-Adema KW, Putter H, Creutzberg CL; PORTEC study group. Adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): final results of an international, open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 Mar;19(3):295-309. doi: 10.1016/S1470-2045(18)30079-2. Epub 2018 Feb 12.

    PubMed 29449189
  • Matei D, Filiaci V, Randall ME, Mutch D, Steinhoff MM, DiSilvestro PA, Moxley KM, Kim YM, Powell MA, O'Malley DM, Spirtos NM, Small W Jr, Tewari KS, Richards WE, Nakayama J, Matulonis UA, Huang HQ, Miller DS. Adjuvant Chemotherapy plus Radiation for Locally Advanced Endometrial Cancer. N Engl J Med. 2019 Jun 13;380(24):2317-2326. doi: 10.1056/NEJMoa1813181.

    PubMed 31189035
  • Wilkinson-Ryan I, Binder PS, Pourabolghasem S, Al-Hammadi N, Fuh K, Hagemann A, Thaker P, Schwarz J, Grigsby P, Mutch D, Powell M. Concomitant chemotherapy and radiation for the treatment of advanced-stage endometrial cancer. Gynecol Oncol. 2014 Jul;134(1):24-8. doi: 10.1016/j.ygyno.2014.05.002. Epub 2014 May 10.

    PubMed 24823648

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Quality of life questionnaire in people with Endometrial Cancer, run by Henry Ford Health System at 1 site in United States.

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 2 inclusion and 3 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: stopped early, as of the sponsor's last update on 29 Mar 2024. 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 United States. 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 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.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 29 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Assessment of Physical and Functional Well-being as Assessed by the FACT-G Questionnaire (time frame: Baseline, 3-month, 6-month, 12-month, 24-month). The study lists 4 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 NCT04743999, which also lists 7 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 29 Mar 2024.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in