SBRT + Atezolizumab for Cervical Cancer

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

21 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Atezolizumab for cervical cancer?

Atezolizumab, a PD-L1 inhibitor, has shown promise in combination with other treatments for advanced cervical cancer, as seen in studies with similar drugs like pembrolizumab, which have demonstrated clinical benefits in patients with recurrent or metastatic cervical cancer. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Atezolizumab for cervical cancer?

Atezolizumab, a PD-L1 inhibitor, has shown promise in treating advanced cervical cancer when combined with other therapies, as seen in studies with similar drugs like pembrolizumab. These drugs have demonstrated clinical benefits in patients with recurrent or metastatic cervical cancer, suggesting potential effectiveness for Atezolizumab as well. ^{1 2 3 4 5}

Is the combination of SBRT and Atezolizumab safe for treating cervical cancer?

There is no specific safety data available for the combination of SBRT and Atezolizumab in cervical cancer. However, Atezolizumab, a PD-L1 inhibitor, has been studied for safety in combination with other treatments for advanced cervical cancer, showing it can be used safely in humans. ^{2 4 5 6 7}

Is the combination of SBRT and Atezolizumab safe for treating cervical cancer?

The safety of Atezolizumab, a PD-L1 inhibitor, has been studied in combination with other treatments for advanced cervical cancer, showing it can be used safely in humans. However, specific safety data for the combination of SBRT (a precise form of radiation therapy) and Atezolizumab in cervical cancer is not available from the provided research. ^{2 4 5 6 7}

How is the drug Atezolizumab unique for treating cervical cancer?

Atezolizumab is unique for treating cervical cancer because it is a PD-L1 antibody that works by helping the immune system recognize and attack cancer cells, and it is being studied in combination with SBRT (a precise form of radiation therapy) to potentially enhance its effectiveness, offering a novel approach compared to traditional chemotherapy. ^{2 4 8 9 10}

What makes the treatment SBRT + Atezolizumab unique for cervical cancer?

SBRT (Stereotactic Body Radiation Therapy) combined with Atezolizumab (an immunotherapy drug that helps the immune system attack cancer cells) is unique because it explores a novel approach by combining precise radiation with a drug that targets the PD-L1 protein, potentially enhancing the immune response against cervical cancer, which is not a standard treatment option currently. ^{2 4 8 9 10}

What is the purpose of this trial?

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) compared with atezolizumab alone in patients with recurrent, persistent, or metastatic cervical cancer.

Research Team

Kamran Ahmed, M.D.

Principal Investigator

H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria

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

I have cancer that has spread to my brain.

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

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Tumor molecular profiling of responders and non-responders following pembrolizumab monotherapy in chemotherapy resistant advanced cervical cancer. [2020]

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

Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Systemic therapy for advanced cervical cancer: Leveraging the historical threshold of overall survival. [2023]

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

Safety and efficacy of nimotuzumab combined with chemoradiotherapy in Chinese patients with locally advanced cervical cancer. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

PD-1/PD-L1 Inhibitors in Cervical Cancer. [2023]

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

Pembrolizumab OK'd for Cervical Cancer. [2019]

7. United States 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. [2022]

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

Bifunctional Blockade: A Novel Immunotherapy Approach for Cervical Cancer. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Exploiting somatic alterations as therapeutic targets in advanced and metastatic cervical cancer. [2022]

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

Current and emerging immunotherapies for recurrent cervical cancer. [2022]