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

Trial Summary

What is the purpose of this trial?

This phase II trial studies if a single session of palliative radiation therapy can help improve symptoms of gynecologic cancers that have spread to other places in the body (metastatic) and that affect quality of life as well or more so than multiple sessions (which is the standard of care). Palliative radiation therapy may help patients with metastatic gynecologic cancers live more comfortably. Researchers also want to learn how radiation affects the immune system and to compare the effects of giving one radiation treatment to giving multiple radiation treatments.

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.

What data supports the effectiveness of this treatment for malignant female reproductive system cancer?

Research shows that stereotactic body radiation therapy (SBRT) has been effective in treating various cancers, including gynecological cancers, by delivering precise, high-dose radiation to tumors. Additionally, intensity-modulated radiotherapy (IMRT) has shown favorable outcomes for cervical cancer, suggesting potential benefits for other female reproductive system cancers. ^{1 2 3 4 5}

Is palliative radiation therapy for malignant female reproductive system cancer generally safe for humans?

Research shows that stereotactic body radiation therapy (SBRT), a type of radiation treatment, is generally safe for treating gynecological cancers, with mild side effects like increased vaginal discharge and no long-term side effects reported in some cases. ^{6 7 8 9 10}

How is the treatment of 3D-CRT, IMRT, and VMAT for malignant female reproductive system cancer different from other treatments?

This treatment uses advanced radiation techniques like 3D-CRT, IMRT, and VMAT, which allow for precise targeting of cancer cells while minimizing damage to surrounding healthy tissue. These methods can reduce side effects compared to traditional radiation therapy and may improve quality of life by allowing higher doses of radiation to be delivered safely. ^{1 11 12 13 14}

Research Team

Lauren Colbert

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

References

1. Greece 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. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Emerging application of stereotactic body radiation therapy for gynecologic malignancies. [2018]

3. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for pelvic boost in gynecological cancer patients with local recurrence or unsuitable for intracavitary brachytherapy. [2021]

4. Germany 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. [2021]

5. United States 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. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy for oligometastatic gynecologic malignancies: A systematic review. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Imaging-Guided Stereotactic Body Radiation Therapy for Medically Inoperable Endometrial Cancer. [2023]

8. Poland 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Comparison of MR-guided radiotherapy accumulated doses for central lung tumors with non-adaptive and online adaptive proton therapy. [2023]

11. England 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. [2018]

12. England 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. [2018]

13. United States 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. [2023]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Whole pelvic intensity-modulated radiotherapy for gynecological malignancies: A review of the literature. [2019]