Ultrafractionated Radiation Therapy for Cervical Cancer

Overseen By Jonathan VanPelt

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Investigational agents

Disqualifiers: Prior pelvic radiation, Inflammatory bowel, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if ultra-fractionated radiation therapy can extend the lives of people with metastatic cervical cancer. The treatment uses a specialized form of radiation, personalized to target cancer in the pelvic area. The trial seeks participants recently diagnosed with cervical cancer that has spread or those with recurring cancer in the pelvis who are undergoing standard systemic treatment. Individuals with stable, treatable brain cancer may still qualify. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, you cannot be on other investigational agents for cancer treatment, and you should discuss your current medications with the trial team to ensure they don't interfere with the study.

What prior data suggests that ultra-fractionated radiation therapy is safe for cervical cancer patients?

Research has shown that ultra-fractionated radiation therapy, which involves administering radiation in smaller, more frequent doses, has generally been well-tolerated in past studies. These studies have examined similar radiation treatments for various cancers, including cervical cancer. In one study, patients who received this type of radiation therapy experienced improvements in disease control and, in some cases, lived longer. Side effects were reported but were often mild and manageable.

Another study on stereotactic body radiation therapy, a related method using precise, high-dose radiation, found it safe and effective for many patients. This suggests that the risks are relatively low, although some unwanted effects may occur, as with any treatment.

Since this trial is in an early phase, it primarily focuses on confirming the safety of this treatment in humans. The treatment has shown enough promise in earlier studies to warrant further testing, but safety remains under close observation. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatment options for cervical cancer, which often involve conventional radiation therapy delivered over several weeks, ultra-fractionated radiation therapy is unique because it delivers higher doses of radiation in fewer sessions. This approach could potentially reduce the overall treatment time significantly. Researchers are excited about this method because it aims to enhance convenience for patients and may minimize the side effects typically associated with prolonged radiation treatments. By concentrating the radiation doses, there's also the possibility of improving the effectiveness of the treatment against cancer cells.

What evidence suggests that ultra-fractionated radiation therapy is effective for cervical cancer?

Research shows that ultrafractionated radiation therapy, studied in this trial, might offer a promising treatment for metastatic cervical cancer. Studies on similar treatments, such as stereotactic body radiation therapy (SBRT), have demonstrated successful cancer control in the targeted area in over 80% of cases. This indicates that the cancer often stops growing where the treatment is applied. SBRT has also proven effective for other tumor types, suggesting it could work well for cervical cancer too. The therapy is generally safe, and most patients tolerate it well. This evidence supports the potential effectiveness of ultrafractionated radiation therapy for cervical cancer. ^{3 4 6 7 8}

Who Is on the Research Team?

Kevin Albuquerque, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed stage IVB cervical cancer that has spread, and who are within 6 months of starting systemic therapy. Participants must have a performance status indicating they can care for themselves (ECOG 0-3) and be able to consent. Women must use birth control during the study. Those with treated or treatable brain metastases may join, but not if they've had pelvic radiation or have certain uncontrolled illnesses.

Inclusion Criteria

I can care for myself but may not be able to do heavy physical work.

Ability to understand and the willingness to sign a written informed consent

I have advanced cervical cancer and started treatment within the last 6 months.

Exclusion Criteria

Subjects may not be receiving any other investigational agents for the treatment of the cancer under study

I have had radiation treatment to my pelvic area.

I do not have active inflammatory bowel or collagen vascular disease, nor am I on immunosuppressants.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead In

An interim safety evaluation will be conducted in a minimum of 10 assessable patients who received at least 3 radiation treatments with 90 days follow up

90 days

3 visits (in-person)

Treatment

Participants receive personalized ultra-fractionated stereotactic adaptive radiotherapy (PULSAR) in 5 treatments

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including local-regional progression and QOL assessments

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Ultra-fractionated radiation therapy

Trial Overview The trial tests ultra-fractionated radiation therapy aimed at improving survival in patients with metastatic cervical cancer. It focuses on treating the local region where the cancer started to see if this approach helps alongside standard systemic treatments.

How Is the Trial Designed?

Group I: Safety Lead In Experimental Treatment 1 Intervention

An interim safety evaluation will be conducted in a minimum of 10 assessable patients who received at least 3 radiation treatments (pulses) with 90 days follow up after radiation OR who experience a dose-limiting toxicity, as defined below. Patients not meeting these requirements will still count towards the overall trial enrollment target, however, the safety lead-in will continue until 10 fully assessable patients are reached (estimate 17 total patients needed for 40% attrition). These patients initially will be enrolled to the base dose-level of 8.5Gy/fraction.

Ultra-fractionated radiation therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Ultra-hypofractionated radiation therapy for:

• Prostate cancer
• Breast cancer
• Cervical cancer

Approved in United States as Ultra-hypofractionated radiation therapy for:

• Prostate cancer
• Breast cancer
• Cervical cancer

Approved in Canada as Ultra-hypofractionated radiation therapy for:

• Prostate cancer
• Breast cancer

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Elekta Limited

Industry Sponsor

Trials

13

Recruited

8,900+

Published Research Related to This Trial

Stereotactic ablative body radiotherapy (SABR) demonstrated a high efficacy in treating inoperable liver tumors, with 72.7% of patients showing partial regression and 27.3% achieving complete remission three months post-treatment.

The treatment was well-tolerated, with no severe toxicity (grade 2 or higher) reported, and resulted in one- and two-year overall survival rates of 85.4% and 68.8%, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided stereotactic ablative radiotherapy for the liver: a safe and effective treatment. Van De Voorde, L., Vanneste, B., Houben, R., et al.[2015]

Stereotactic ablative radiation therapy (SAbR) was assessed as a potential alternative to brachytherapy for patients with locally advanced cervical cancer, but the study faced challenges with safety and efficacy, leading to the closure of the trial after 15 of 21 patients completed it due to toxicity concerns.

The 2-year survival rates were lower than expected, with local control at 70.1% and significant grade ≥ 3 toxicity (26.7%) primarily affecting the rectum, indicating that patient selection and tumor size are critical factors in determining the success of SAbR in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Trial of Stereotactic Ablative Radiation Therapy as a Boost for Locally Advanced Cervical Cancer. Albuquerque, K., Tumati, V., Lea, J., et al.[2020]

Recent advancements in radiation therapy for cervical cancer, such as intensity-modulated radiation therapy (IMRT) and image-guided brachytherapy (IGBT), are improving local control of the disease while reducing toxicity to normal tissues.

The shift towards IGBT and three-dimensional volume-based prescriptions is leading to better treatment outcomes, and SBRT is emerging as a potential option for patients with limited metastases, although more research is needed to confirm its efficacy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Moving from standardized to personalized boxes and pears in radiation planning for cervical cancer. Mesko, S., Kamrava, M.[2015]

Stereotactic ablative body radiotherapy (SABR) boost for cervical cancer patients who cannot undergo brachytherapy showed promising efficacy, with 3-year local control and overall survival rates of 80.9% and 77.1%, respectively, based on a study of 25 patients.

The treatment was generally well-tolerated, with only 5 patients experiencing grade 3 toxicity, and no severe grade 4-5 toxicities reported, indicating that SABR boost can be a safe alternative when brachytherapy is not an option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy boost for cervical cancer when brachytherapy boost is not feasible. Lee, TH., Song, C., Kim, IA., et al.[2022]

Stereotactic body radiation therapy (SBRT) using helical tomotherapy (HT) showed a 78% locoregional control rate at 3 years for nine cervical cancer patients who were unsuitable for brachytherapy, indicating its efficacy as a treatment option.

While two patients experienced significant acute toxicity, the overall safety profile was acceptable, with manageable side effects and no severe long-term toxicities reported, suggesting that SBRT via HT is a viable alternative for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy via helical tomotherapy to replace brachytherapy for brachytherapy-unsuitable cervical cancer patients - a preliminary result. Hsieh, CH., Tien, HJ., Hsiao, SM., et al.[2022]

Stereotactic ablative radiotherapy (SABR) has been shown to be feasible and well tolerated for low- and intermediate-risk prostate cancer patients, with promising results from large randomized studies comparing it to conventional treatments.

While SABR shows potential benefits and cost-effectiveness, there is currently insufficient data to recommend its use for high-risk prostate cancer patients outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. Loblaw, A.[2021]

In a study of 102 patients receiving stereotactic ablative radiotherapy (SABR) for lung cancer and lung oligometastases, the three-year local control rates were 85% for primary lung cancer and 82% for metastatic lesions, which are comparable to global outcomes.

No severe toxicities (grade three) were reported, indicating that SABR is a safe treatment option, although Māori patients with primary lung cancer experienced significantly worse progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for early stage lung cancer and lung metastases in a New Zealand population. Geary, RL., Yasin, NABH., Lin, F., et al.[2021]

Stereotactic ablative radiation therapy (SABR) for stage I lung cancer at Sheba Medical Center showed a median overall survival of 46 months and a 3-year survival rate of 59%, indicating its efficacy as a treatment for inoperable patients.

The treatment demonstrated excellent local control at 88% and had manageable toxicity, with only 8.4% of patients experiencing chest wall pain and a low incidence of severe side effects, suggesting it is a safe option for patients with early-stage lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report. Appel, S., Lawrence, YR., Goldstein, J., et al.[2022]

Stereotactic Ablative Radiotherapy (SABR) for central and ultra-central lung tumors shows promising outcomes, with median overall survival of 46 months and disease-free survival of 33 months among 137 patients treated between 2009 and 2016.

While central tumors had a better prognosis (median OS of 57 months) compared to ultra-central tumors (37 months), both types had high local control rates (95% at 1 year and 81% at 2 years) and relatively low severe toxicity rates (7.3% grade 3-5 toxicities).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk-adapted stereotactic ablative radiotherapy for central and ultra-central lung tumours. Lenglet, A., Campeau, MP., Mathieu, D., et al.[2020]

Stereotactic ablative radiotherapy (SABR) for re-irradiation of recurrent pelvic cancer shows promise, with local control rates ranging from 51% to 100% in a review of 205 patients across 17 studies, although the studies were mostly small and retrospective.

The treatment appears to be well-tolerated, with only a few cases of severe toxicities (grade 3 and 4), suggesting that SABR could be a feasible option for patients with limited treatment choices, but more prospective studies are needed to establish a formal treatment pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review. Murray, LJ., Lilley, J., Hawkins, MA., et al.[2023]

Citations

1. withpower.com withpower.com/trial/phase-3-carcinoma-adenosquamous-9-2021-12c59

Ultrafractionated Radiation Therapy for Cervical Cancer Stereotactic ablative body radiotherapy (SABR) demonstrated a high efficacy in treating inoperable liver tumors, with 72.7% of patients showing partial ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10340138/

Stereotactic Body Radiation Therapy in Gynecologic ... The current literature shows that SBRT in gynecologic oligometastases is safe and effective, resulting in 2-year local control rates exceeding 80%.

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24010028

Stereotactic body radiotherapy in oligometastatic cervical ... This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiotherapy in a large cohort of patients with ...

4. e-roj.org e-roj.org/include/download.php?filedata=1598%7Croj-2023-01046.pdf

exploring efficacy and safety-Part 3. Genitourinary a Hypofractionated radiotherapy (RT) has become a trend in the modern era, as advances in RT tech- niques, including intensity-modulated RT ...

5. ro-journal.biomedcentral.com ro-journal.biomedcentral.com/articles/10.1186/s13014-021-01877-4

Stereotactic ablative body radiotherapy boost for cervical ... SABR boost for cervical cancer was effective and tolerable. Although it cannot substitute brachytherapy, it can be a treatment option when brachytherapy is not ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11467485/

Evidence-based clinical recommendations for ... In this review, we aimed to summarize the representative evidence and current trends in clinical studies on hypofractionated RT for GU and GY cancers ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05021237

Personalized Ultra-fractionated Stereotactic Adaptive ... Improvements in disease control, prevention of morbid local symptoms and even survival have been demonstrated when treating the primary in other cancer types 3, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11844808/

Current State of Stereotactic Body Radiation Therapy for ... Stereotactic body radiation therapy (SBRT) involves the delivery of high-dose, highly precise radiation therapy to focal sites of gross tumor involvement.