SBRT + Atezolizumab for Cervical Cancer

Not currently recruiting at 1 trial location

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Brain metastasis, Autoimmune disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining atezolizumab, an immune system-boosting drug, with a precise form of radiation therapy called SBRT (Stereotactic Body Radiation Therapy) can improve treatment outcomes for cervical cancer compared to using atezolizumab alone. It targets individuals with cervical cancer that has recurred, is persistent, or has metastasized. Participants must have at least two measurable cancerous lesions and be willing to undergo a biopsy. The study seeks individuals dealing with these specific forms of cervical cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications (drugs that lower the body's immune response) at least 2 weeks before starting the study treatment. However, some exceptions apply, such as low-dose or short-term use of certain medications.

Will I have to stop taking my current medications?

The trial requires that you stop taking systemic immunosuppressive medications (like certain steroids or drugs that suppress the immune system) at least 2 weeks before starting the study treatment. However, some exceptions apply, such as low-dose or short-term use of these medications.

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

Research has shown that combining atezolizumab with stereotactic body radiation therapy (SBRT) is generally safe for patients with metastatic cervical cancer. A recent study found no major safety concerns with this treatment. Atezolizumab, an immunotherapy, aids the immune system in fighting cancer, while SBRT targets tumors with high-dose radiation. This combination has been tested in individuals with similar conditions, yielding positive safety results, with no severe or unexpected side effects. For those considering participation in a trial with this treatment, earlier studies have found it manageable for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of stereotactic body radiation therapy (SBRT) followed by atezolizumab for cervical cancer because it introduces a novel approach to treatment. While standard care often involves chemotherapy and radiation, this combination leverages the precision of SBRT to target tumors with high doses of radiation, followed by atezolizumab, an immunotherapy drug that encourages the immune system to attack cancer cells. This approach not only aims to minimize damage to healthy tissues, but also enhances the body's natural defenses against cancer, potentially leading to improved outcomes compared to traditional treatments.

What evidence suggests that SBRT + Atezolizumab could be effective for cervical cancer?

In this trial, participants will receive a combination therapy of Stereotactic Body Radiation Therapy (SBRT) followed by atezolizumab. Research has shown that atezolizumab can effectively treat cervical cancer, with patients remaining cancer-free for an average of 13.7 months, compared to 10.4 months for those not receiving the drug. This suggests that atezolizumab extends the period patients remain free of cancer.

Stereotactic Body Radiation Therapy (SBRT) has also shown promise in controlling cervical cancer. While it cannot completely replace other treatments, SBRT has been effective in managing and reducing tumor size. Together, these treatments offer hope for those with cervical cancer that has recurred or spread to other parts of the body. ^{6 7 8 9 10}

Who Is on the Research Team?

Kamran Ahmed, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Are You a Good Fit for This Trial?

This trial is for adults with recurrent, persistent, or metastatic cervical cancer who are in good enough health to undergo treatment (ECOG ≤ 2 or Karnofsky ≥ 60). They must have measurable disease and at least two distinct lesions. Those with a history of certain other cancers within the last two years, active autoimmune diseases, immune deficiencies, or recent systemic immunosuppressive treatments cannot participate.

Inclusion Criteria

My cancer has grown at a site previously treated with radiation.

I agree to a biopsy or providing previous biopsy samples.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I have cancer that has spread to my brain.

I haven't had cancer, except for certain low-risk types, in the last 2 years.

I do not have an active autoimmune disease or immune deficiency, except for controlled thyroid issues or type 1 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic body radiation therapy (SBRT)

1 week

1 visit (in-person)

Treatment

Participants receive atezolizumab following SBRT

Up to 24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Stereotactic body radiation therapy (SBRT)

Trial Overview The study aims to determine if combining Atezolizumab (an immunotherapy drug) with Stereotactic Body Radiation Therapy (SBRT), which is a precise high-dose radiation therapy, can improve response rates in patients compared to using Atezolizumab alone for treating cervical cancer.

How Is the Trial Designed?

Group I: Combination Therapy Experimental Treatment 2 Interventions

Stereotactic body radiation therapy (SBRT) followed by atezolizumab, 1 week later.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a study of 80 women with locally advanced cervical cancer, nimotuzumab combined with chemotherapy and radiotherapy showed a disease control rate of 88%, indicating it can effectively stabilize the disease in most patients.

The treatment was well tolerated, with median progression-free survival of 8.21 months and median overall survival of 11.96 months, suggesting it may be a viable alternative for patients who have relapsed after initial therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of nimotuzumab combined with chemoradiotherapy in Chinese patients with locally advanced cervical cancer. Chen, YF., Tang, WB., Pan, XX., et al.[2020]

Cervical cancer remains a significant global health issue, particularly in low- and middle-income countries, where patients often present with advanced disease.

Recent advancements in treatment, particularly the use of immunotherapy (pembrolizumab), have improved overall survival rates for patients with advanced cervical cancer, establishing it as the standard of care in both first-line and second-line treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic therapy for advanced cervical cancer: Leveraging the historical threshold of overall survival. Paulino, E., de Melo, AC., de Andrade, DAP., et al.[2023]

SHR-1701, a bispecific fusion protein targeting PD-L1 and TGFβ, shows promising clinical activity in patients with advanced or recurrent cervical cancer.

This study provides proof of principle that targeting the TGFβ pathway with bispecific antibodies could be an effective new therapeutic strategy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer. Miller, KM., Friedman, CF.[2023]

In a phase II study involving 10 patients with advanced cervical cancer, the combination of atezolizumab and bevacizumab resulted in an objective response rate (ORR) of 0%, indicating that this treatment did not effectively shrink tumors as hoped.

Despite the lack of confirmed responses, the disease control rate was 60%, with a median progression-free survival of 2.9 months and overall survival of 8.9 months, suggesting some patients experienced stable disease, although safety concerns included two high-grade neurologic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. Friedman, CF., Snyder Charen, A., Zhou, Q., et al.[2021]

In a study of 4 patients with advanced cervical cancer treated with pembrolizumab, all patients tolerated the treatment well, with one patient achieving a remarkable 21-month progression-free survival, indicating potential efficacy of this PD-1 inhibitor.

Biomarker analysis revealed that patients with a combined positive score (CPS) for PD-L1 of ≥1 and specific somatic mutations, such as in PIK3CA, may benefit from pembrolizumab, suggesting that further research into predictive biomarkers could enhance patient selection for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. Ngoi, NYL., Heong, V., Lee, XW., et al.[2020]

Pembrolizumab, a PD-1 inhibitor, has been approved by the FDA as a second-line treatment for recurrent or metastatic cervical cancer in patients with a PD-L1 combined positive score of at least 1.

In a phase II trial, pembrolizumab demonstrated an objective response rate of 14.3%, indicating its potential efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab OK'd for Cervical Cancer. [2019]

PD-1/PD-L1 inhibitors, such as pembrolizumab, have been approved by the FDA for treating recurrent or metastatic cervical cancer, showing established clinical benefits in pivotal trials like Keynote 028 and Checkmate 358.

These inhibitors represent a promising new treatment option for patients with cervical cancer who have limited effective therapies available, particularly after chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors in Cervical Cancer. Liu, Y., Wu, L., Tong, R., et al.[2023]

Cervical cancer affects a significant number of patients, with 15-61% developing advanced disease after diagnosis, and current treatment options have not improved the 5-year survival rate over the last 30 years.

Recent advancements in tumor genomic testing have identified a 28.4% actionability rate for targetable mutations in cervical cancer, indicating potential for personalized treatment strategies using targeted agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer. Crowley, FJ., O'Cearbhaill, RE., Collins, DC.[2022]

In 2021, the approval of pembrolizumab, both alone and in combination with chemotherapy, marked a significant advancement in the treatment of advanced cervical cancer, providing new options for patients with recurrent or metastatic disease.

Upcoming approvals for other PD-1 inhibitors, like cemiplimab, and ongoing research into combination immunotherapies suggest a promising future for cervical cancer treatment, particularly in enhancing efficacy and overcoming resistance to current therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and emerging immunotherapies for recurrent cervical cancer. Liu, MC., Tewari, KS.[2022]

In a phase II trial involving 161 women with recurrent or metastatic cervical cancer, balstilimab, an anti-PD-1 antibody, showed an objective response rate (ORR) of 15%, indicating it can provide meaningful antitumor activity in this patient population.

The treatment was generally safe, with manageable side effects; the most common severe adverse events were immune-mediated enterocolitis (3.1%) and diarrhea (1.9%), suggesting that balstilimab has a favorable safety profile for patients who have previously undergone platinum-based therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. O'Malley, DM., Oaknin, A., Monk, BJ., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11200956/

Efficacy and Safety of Atezolizumab as a PD-L1 Inhibitor in ... Data indicated that atezolizumab provided a complete response of 6% in solid cancers and a partial response rate of 16% with a median ...

2. targetedonc.com targetedonc.com/view/atezolizumab-efficacy-in-cervical-cancer-consistent-irrespective-of-pd-l1

Atezolizumab Efficacy in Cervical Cancer Consistent ... The initial results demonstrated a median PFS of 13.7 months (95% CI, 12.3-16.6) in the atezolizumab arm compared with 10.4 months (95% CI, 9.7- ...

3. onclive.com onclive.com/view/pd-l1-cps-does-not-enrich-the-efficacy-of-atezolizumab-bevacizumab-and-chemo-in-advanced-cervical-cancer

PD-L1 CPS Does Not Enrich the Efficacy of Atezolizumab/ ... In patients with a CPS of less than 1, the median OS was 37.3 months with atezolizumab vs 19.2 months without (HR, 0.43; 95% CI, 0.24-0.77). “ ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39466967/

Cost-effectiveness analysis of atezolizumab plus ... Adding atezolizumab to chemotherapy is cost-prohibitive in the US and may not be cost-effective for patients.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X24000203

A non-comparative, randomized, phase II trial of ... At 8.5 months' median follow-up, independent review committee-assessed progression-free survival was 2.8 months (95% CI 1.7 to 4.1) with tiragolumab plus ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40379142/

Atezolizumab and Stereotactic Body Radiation in Metastatic ... In this first trial of SBRT and atezolizumab in metastatic cervical cancer unselected for PD-L1, combination therapy was well tolerated.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03614949

Study Details | NCT03614949 | SBRT and Atezolizumab in ... The purpose of this study is to see if treatment with atezolizumab and stereotactic body radiation therapy (SBRT) will improve the objective response rate (ORR) ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-00233

Stereotactic Body Radiation Therapy and Atezolizumab in ... This phase II trial studies how well stereotactic body radiation therapy (SBRT) and atezolizumab works in treating patients with cervical, vaginal, ...

9. redjournal.org redjournal.org/cms/10.1016/j.ijrobp.2025.05.003/attachment/59d6aa31-9133-49ac-8d9b-7c6d55105900/mmc1.pdf

PROTOCOL Protocol Title: Phase II study of stereotactic body radiation therapy and atezolizumab in the management of recurrent, persistent, or metastatic cervical cancer.

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7378931/

Radiobiology of stereotactic ablative radiotherapy (SABR) SABR is a novel radiation treatment method that delivers an intense dose of radiation to the treatment targets with high accuracy.