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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

To improve overall survival in patients with metastatic cervical cancer by loco-regional therapy with personalized ultra-fractionated radiation

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 data supports the effectiveness of ultrafractionated radiation therapy for cervical cancer?

Research shows that stereotactic ablative body radiotherapy (SABR), a component of ultrafractionated radiation therapy, is effective and safe as a boost for cervical cancer when traditional brachytherapy is not possible. This suggests that ultrafractionated radiation therapy could be a promising option for treating cervical cancer. ^{1 2 3 4 5}

Is ultrafractionated radiation therapy generally safe for humans?

Stereotactic ablative body radiotherapy (SABR), a form of ultrafractionated radiation therapy, has been shown to be safe and well-tolerated in treating various conditions like liver tumors, prostate cancer, and lung cancer, with careful planning and setup techniques. ^{2 4 6 7 8}

How is ultrafractionated radiation therapy different from other treatments for cervical cancer?

Ultrafractionated radiation therapy, also known as stereotactic body radiation therapy (SBRT) or stereotactic ablative body radiation (SABR), is unique because it delivers high doses of radiation in fewer sessions with high precision, making it a potential alternative for patients who cannot undergo brachytherapy. This approach can be more convenient and cost-effective, and it has been shown to be feasible and well-tolerated in clinical trials. ^{2 4 5 9 10}

Research Team

Kevin Albuquerque, MD

Principal Investigator

UT Southwestern Medical Center

Eligibility Criteria

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.

I am 18 years old or older.

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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 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]

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) 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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy for early stage lung cancer and lung metastases in a New Zealand population. [2021]

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

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Pelvic re-irradiation using stereotactic ablative radiotherapy (SABR): A systematic review. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy boost for cervical cancer when brachytherapy boost is not feasible. [2022]

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

A Phase II Trial of Stereotactic Ablative Radiation Therapy as a Boost for Locally Advanced Cervical Cancer. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Image-guided stereotactic ablative radiotherapy for the liver: a safe and effective treatment. [2015]

7. Israel pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiation for Stage I Lung Cancer in Israel: A Retrospective Single-Center Report. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Risk-adapted stereotactic ablative radiotherapy for central and ultra-central lung tumours. [2020]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy via helical tomotherapy to replace brachytherapy for brachytherapy-unsuitable cervical cancer patients - a preliminary result. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Moving from standardized to personalized boxes and pears in radiation planning for cervical cancer. [2015]