Palliative Radiation Therapy for Malignant Female Reproductive System Cancer

Recruiting at 2 trial locations

Overseen By Lauren Colbert

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Systemic therapy

Disqualifiers: Prior pelvic radiation, Second malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

108 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a single session of radiation therapy can ease symptoms of certain metastatic female reproductive system cancers, compared to the usual multiple sessions. The goal is to improve patient comfort and assess the impact on the immune system. The trial includes two groups: one receiving a single radiation treatment and the other receiving multiple treatments. Women with a confirmed diagnosis of metastatic gynecologic cancer who experience pain or bleeding might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop any systemic therapy (treatment affecting the whole body) at least 21 days before starting radiation. If you are on such medications, you will need to stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the three types of radiation therapy under study—3-Dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), and Volume Modulated Arc Therapy (VMAT)—are generally safe for treating gynecologic cancers.

3D-CRT has demonstrated safety with low levels of side effects in patients with gynecological cancer. It does not cause severe side effects, and patients have reported a better quality of life after treatment.

IMRT is another promising option. Research indicates that it can precisely target cancer while protecting healthy tissues. This precision helps reduce treatment interruptions and is linked to an improved quality of life for patients.

VMAT is a newer radiation technique. Studies have shown it can deliver radiation in a very targeted way, leading to fewer side effects and better outcomes for patients.

Overall, these treatments have been well-tolerated by patients in past studies, demonstrating safety and effectiveness in managing symptoms of gynecologic cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the different radiation therapy approaches being explored for malignant female reproductive system cancers because they offer potential improvements in treatment flexibility and effectiveness. Unlike traditional radiation treatments that typically require multiple sessions over several weeks, the experimental arm allows for a single radiation dose with the possibility of a second dose based on individual response, potentially reducing treatment time and burden on patients. Additionally, the use of advanced techniques like Intensity-Modulated Radiation Therapy (IMRT) and Volume Modulated Arc Therapy (VMAT) allows for more precise targeting of tumors, which could minimize damage to surrounding healthy tissues and reduce side effects. This approach aims to tailor treatment to the individual's needs, potentially leading to better outcomes and enhanced quality of life.

What evidence suggests that this trial's radiation therapies could be effective for metastatic gynecologic cancers?

This trial compares different radiation therapy approaches for treating gynecologic cancers. Studies have shown that 3D Conformal Radiation Therapy (3D-CRT), one of the treatments in this trial, accurately targets tumors, which is crucial for preventing cancer spread. Intensity-Modulated Radiation Therapy (IMRT), another treatment option, has shown better results in controlling cancer and improving survival, especially when other treatments have failed. Volume Modulated Arc Therapy (VMAT), also tested in this trial, delivers precise treatment while protecting healthy tissues, resulting in fewer side effects. These treatments have improved quality of life by reducing pain and other symptoms in patients with advanced gynecologic cancers. ^{1 6 7 8 9}

Who Is on the Research Team?

Lauren Colbert

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for women with metastatic gynecologic cancers experiencing pain or bleeding. Participants must have a life expectancy over 3 months, be able to consent, and use contraception if of childbearing potential. Exclusions include prior pelvic radiation, active participation in other interventional radiation trials within 30 days, psychiatric disorders affecting trial compliance, pregnancy or breastfeeding through 120 days post-treatment.

Inclusion Criteria

Patient able to provide properly obtained written informed consent

My gynecologic cancer has spread, confirmed by tests.

I have pelvic disease causing pain or bleeding that can be measured.

Exclusion Criteria

I have another cancer that needs treatment, as decided by my doctor.

Documented psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

I haven't had systemic therapy in the last 21 days before my first radiation dose.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Therapy

Patients undergo either single fraction or multi-fraction palliative radiation therapy to improve quality of life

2-3 weeks

1-10 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life improvements after radiation therapy

Up to 1 year

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• 3-Dimensional Conformal Radiation Therapy
• Intensity-Modulated Radiation Therapy
• Volume Modulated Arc Therapy

Trial Overview The study compares single-session palliative radiation therapy's effectiveness against multiple sessions (standard care) for symptom relief in metastatic gynecologic cancer patients. It also examines the impact on the immune system and quality of life using various advanced radiation techniques.

How Is the Trial Designed?

Group I: Arm A (radiation therapy) Experimental Treatment 5 Interventions

Patients undergo standard of care radiation therapy in the form of 3D CRT, IMRT, or VMAT at the physician's discretion for 1 fraction in the absence of disease progression or unacceptable toxicity. Patients with \< 30% decrease in the SIS may receive an additional fraction on day 21 at the physician's discretion.

Group II: Arm B (radiation therapy) Active Control 5 Interventions

Patients undergo standard of care radiation therapy in the form of 3D CRT, IMRT, or VMAT at the physician's discretion over 2 weeks for 10 fractions in the absence of disease progression or unacceptable toxicity.

3-Dimensional Conformal Radiation Therapy is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in European Union as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Canada as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Japan as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in China as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Approved in Switzerland as 3D-CRT for:

• Various types of cancer, including gynecologic cancers

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 55 patients with painful spinal metastases, stereotactic body radiotherapy (SBRT) did not show significant differences in quality of life, fatigue, or emotional distress compared to conventional three-dimensional conformal radiotherapy (3DCRT) at multiple follow-up points.

The findings suggest that SBRT is not associated with worse quality of life outcomes compared to 3DCRT, indicating its potential as a safe palliative treatment option, but further research with larger sample sizes is needed to confirm these results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life Following Stereotactic Body Radiotherapy Versus Three-Dimensional Conformal Radiotherapy for Vertebral Metastases: Secondary Analysis of an Exploratory Phase II Randomized Trial. Sprave, T., Verma, V., Förster, R., et al.[2018]

In a study of 60 patients with spinal metastases, both intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) resulted in significant increases in bone density after 3 and 6 months, with no significant differences between the two methods.

IMRT showed improved pain relief at 3 months compared to baseline, but this effect did not persist at 6 months, while overall pain response was similar between IMRT and 3DCRT at both time points.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone density and pain response following intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for vertebral metastases - secondary results of a randomized trial. Sprave, T., Verma, V., Förster, R., et al.[2018]

Intensity-modulated radiation therapy (IMRT) significantly improves dose conformity and reduces radiation exposure to critical organs like the rectum and bladder compared to conformal radiotherapy (CRT) and 4-field box boost (4FB) in women with gynecologic cancers.

In a study of 12 patients, IMRT reduced the volume of the rectum receiving high doses by 22% and the bladder by 19%, which may lead to fewer side effects, although some patients still experienced grade 3 rectal bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric comparison of intensity-modulated, conformal, and four-field pelvic radiotherapy boost plans for gynecologic cancer: a retrospective planning study. Chan, P., Yeo, I., Perkins, G., et al.[2018]

In a study involving 18 patients with early-stage central lung tumors, online adaptive intensity modulated proton therapy (IMPT) significantly reduced the mean dose to the bronchial tree compared to MR-guided radiotherapy (MRgRT), suggesting a safer treatment option with lower toxicity risks.

Both non-adaptive and online adaptive IMPT showed significant reductions in the mean doses to the ipsilateral lung and heart compared to MRgRT, indicating improved dose sparing for organs-at-risk during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. Rabe, M., Palacios, MA., van Sörnsen de Koste, JR., et al.[2023]

Volumetric modulated arc therapy (VMAT) provides comparable or better target volume coverage for gynaecological cancers than intensity modulated radiation therapy (IMRT), with similar planning target volume (PTV) metrics.

VMAT significantly spares organs at risk (OAR) more effectively than IMRT, resulting in lower doses to critical areas like the bowel and bladder, while also reducing treatment delivery times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of volumetric modulated arc therapy (VMAT) in gynaecological radiation therapy: A dosimetric comparison of intensity modulated radiation therapy versus VMAT. Knapp, P., Eva, B., Reseigh, G., et al.[2023]

Stereotactic body radiation therapy (SBRT) shows high efficacy for treating oligometastatic gynecologic cancers, with response rates ranging from 49% to 97% and local control rates of 71% to 100% across multiple studies involving 667 patients.

While SBRT is generally safe, with no severe toxicities reported in over half of the studies, there is a notable risk of disease progression occurring outside the treated areas, indicating the need for further research into combining SBRT with systemic therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for oligometastatic gynecologic malignancies: A systematic review. Yegya-Raman, N., Cao, CD., Hathout, L., et al.[2021]

In a study of 205 prostate cancer patients treated with stereotactic body radiation therapy (SBRT), 99% completed the treatment without severe acute side effects, indicating that this method is safe and well-tolerated.

The most common acute side effects were mild to moderate, with 50.7% experiencing grade II genitourinary issues and 31.7% experiencing grade I gastrointestinal issues, but no patients had severe (grade ≥ 4) toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute side effects after definitive stereotactic body radiation therapy (SBRT) for patients with clinically localized or locally advanced prostate cancer: a single institution prospective study. Jorgo, K., Polgar, C., Stelczer, G., et al.[2022]

In a study of 25 gynecological cancer patients, stereotactic body radiotherapy (SBRT) for pelvic boost irradiation resulted in a 72% initial response rate, indicating its efficacy for patients with pelvic recurrence or those unsuitable for brachytherapy.

The 1-year in-field relapse-free survival rates were 64.5% for the salvage group and 90.0% for the definitive group, with acceptable early toxicities, including only one case of serious complication, suggesting SBRT is a safe option for local dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for pelvic boost in gynecological cancer patients with local recurrence or unsuitable for intracavitary brachytherapy. Cheng, HY., Liang, JA., Hung, YC., et al.[2021]

In a study of six medically inoperable endometrial cancer patients, triple-tandem high-dose-rate (HDR) brachytherapy resulted in mild acute toxicity, indicating it is a safe treatment option for patients with significant comorbidities.

HDR brachytherapy delivered lower doses to surrounding normal tissues compared to stereotactic body radiotherapy (SBRT), suggesting it may be a more effective option for minimizing damage to healthy organs during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triple-tandem high-dose-rate brachytherapy for early-stage medically inoperable endometrial cancer: Initial report on acute toxicity and dosimetric comparison to stereotactic body radiation therapy. Kauffmann, G., Wu, T., Al-Hallaq, H., et al.[2018]

Stereotactic body radiotherapy (SBRT) for women with oligometastatic gynecological tumors showed a high local control rate of 92.5% at both 12 and 24 months, indicating its efficacy in managing localized metastases.

The treatment was associated with low toxicity, with no severe acute side effects (grade > 3) and only mild late effects, suggesting that SBRT is a safe option for patients with oligometastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience. Smile, TD., Reddy, CA., Qiao-Guan, G., et al.[2022]

Stereotactic body radiation therapy (SBRT) has shown clinical efficacy in treating early-stage non-small-cell lung cancer and oligometastases in the lung and liver, leading to its exploration in gynecological cancers.

The article reviews key clinical trials and discusses the potential new therapeutic roles of SBRT in managing persistent or recurrent gynecological cancers, highlighting its growing importance in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging application of stereotactic body radiation therapy for gynecologic malignancies. Mayr, NA., Huang, Z., Sohn, JW., et al.[2018]

In a study comparing volumetric modulated arc therapy (VMAT) to conventional 3D conformal radiotherapy (3DCRT) in cervical cancer patients, VMAT significantly reduced late small bowel toxicity, suggesting a potential improvement in long-term patient outcomes.

However, VMAT was associated with a higher risk of acute urinary toxicity, indicating that while it may reduce certain long-term side effects, it could lead to more immediate complications, particularly in patients with low body mass index (BMI) or those experiencing significant acute toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conventional 3D conformal radiotherapy and volumetric modulated arc therapy for cervical cancer: Comparison of clinical results with special consideration of the influence of patient- and treatment-related parameters. Dröge, LH., von Sivers, FF., Schirmer, MA., et al.[2021]

Intensity-modulated radiotherapy (IMRT) is increasingly being used to treat gynecological cancers, showing promise in reducing side effects like gastrointestinal and genitourinary toxicities compared to traditional 3D-conformal radiotherapy.

IMRT allows for higher doses of radiation and better chemotherapy intensification, which may improve treatment outcomes, with ongoing trials focusing on its application for cervical and endometrial cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Whole pelvic intensity-modulated radiotherapy for gynecological malignancies: A review of the literature. Hymel, R., Jones, GC., Simone, CB.[2019]

An 86-year-old woman with early-stage endometrial carcinoma, who was medically inoperable, successfully underwent stereotactic body radiotherapy (SBRT) and achieved complete metabolic and radiological responses.

The treatment was well-tolerated with only mild side effects, and the patient remained disease-free after one year, suggesting that SBRT could be a safe and effective option for patients with inoperable early-stage endometrial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Imaging-Guided Stereotactic Body Radiation Therapy for Medically Inoperable Endometrial Cancer. Dincer, N., Abacioglu, UM., Tezcanli, E., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-3-genital-neoplasms-female-2021-5c647

Palliative Radiation Therapy for Malignant Female ... Research shows that stereotactic body radiation therapy (SBRT) has been effective in treating various cancers, including gynecological cancers, by delivering ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12422066/

3D Conformal Radiotherapy Versus the Conventional Box ... Results: The 3D-CRT demonstrated significantly higher conformity (CI: 0.92 ± 0.03; p=0.001) and better homogeneity (HI: 0.08 ± 0.01; p=0.002) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452109420302232

Outcomes After Salvage Radiation Therapy for Recurrent ... Our study demonstrates that localized recurrence of endometrial cancer after surgery with initial observation can be successfully salvaged with good control ...

4. nature.com nature.com/articles/s41598-020-74356-7

Clinical analysis of conformal and intensity-modulated ... Compared with normal three-dimensional conformal radiotherapy (3D-CRT), IMRT can provide better dose distribution and reduce the dose of organs ...

5. cureus.com cureus.com/articles/3663-intensity-modulated-radiation-therapy-versus-3d-conformal-radiotherapy-for-postoperative-gynecologic-cancer-are-they-covering-the-same-planning-target-volume

Intensity-Modulated Radiation Therapy Versus 3D ... Pelvic radiotherapy has been classically delivered with three-dimensional conformal radiation therapy (3DCRT) using a four-field (4FLD) box ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7358686/

The efficacy of three-dimensional conformal radiation ... The patients experienced significant pain response and improved QoL compared with baseline, especially in the first two weeks after radiation.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12014840/

Efficacy of palliative hemostatic radiotherapy for tumor ... Palliative hemostatic radiotherapy for locally advanced pelvic gynecological malignancies is safe and effective in achieving high control rates of hemostasis in ...

8. jsurgmed.com jsurgmed.com/article/view/421803

Acute toxicities of three-dimensional conformal ... Conclusion: 3D-CRT is a safe treatment with acceptable low toxicity levels in gynecological cancer patients, and it does not adversely affect ...

9. my.clevelandclinic.org my.clevelandclinic.org/health/procedures/3d-conformal-radiation-therapy-3d-crt

3D-CRT (Three-Dimensional Conformal Radiation Therapy) By using 3D-CRT, radiation oncologists get a three-dimensional view of cancerous tumors and nearby healthy organs. That perspective helps them map a tumor's ...