Atezolizumab + Chemoradiotherapy for Cervical Cancer

No longer recruiting at 16 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, RANKL inhibitors

Disqualifiers: Prior radiation, Transplantation, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 10

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding atezolizumab, an immunotherapy drug, to standard chemoradiotherapy can improve treatment for certain cervical cancer patients. The goal is to determine if this combination can activate the immune system to better attack the cancer and prevent its spread. Participants are divided into two groups: one receives atezolizumab before and with chemoradiotherapy, and the other receives it only with chemoradiotherapy. The trial seeks participants with advanced cervical cancer that has spread to the lymph nodes. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on systemic immunosuppressive medications, you must stop them at least 2 weeks before starting the trial. Also, if you are taking a RANKL inhibitor, you need to discontinue it before treatment with atezolizumab.

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

Research has shown that when combined with other treatments, atezolizumab often leads to side effects in many patients. In one study on cervical cancer, 79% of patients experienced severe side effects. Despite this, treatment plans frequently include atezolizumab, and it is generally considered well-tolerated.

Cisplatin, the chemotherapy drug in this trial, is widely used in cancer treatment and is known for its safety. It is usually tolerable when combined with other treatments for advanced cervical cancer.

Studies have indicated that radiation therapy and brachytherapy are effective and safe for treating cervical cancer, often resulting in good outcomes with manageable side effects.

In summary, while there is a risk of side effects, these treatments have been used in various ways and are generally manageable. Always consult a healthcare professional for personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using atezolizumab in combination with chemoradiotherapy for cervical cancer because it introduces a novel approach to treatment. Atezolizumab is an immunotherapy drug that works by blocking the PD-L1 protein, which can help the immune system recognize and attack cancer cells more effectively. This is different from the traditional chemotherapy and radiation treatments, which primarily aim to kill cancer cells directly. By combining atezolizumab with cisplatin and radiation therapy, there's potential for a more robust immune response against the cancer, possibly improving outcomes for patients. This combination approach is what sets it apart from the standard treatments, which typically don't engage the immune system in this way.

What evidence suggests that this trial's treatments could be effective for cervical cancer?

This trial will evaluate the combination of atezolizumab, a type of immunotherapy, with standard treatments for cervical cancer. Research has shown that atezolizumab can improve outcomes for cervical cancer patients, with some living an average of 13.7 months without cancer progression. In this trial, participants will receive atezolizumab alongside standard treatments like cisplatin (a chemotherapy drug) and radiation therapy. Cisplatin is known to improve survival rates, especially at higher doses. Radiation therapy, particularly when combined with brachytherapy (a targeted form of radiation), effectively reduces cancer death rates and improves patient outcomes. Together, these treatments offer a promising approach to managing cervical cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Jyoti S Mayadev

Principal Investigator

NRG Oncology

Are You a Good Fit for This Trial?

This trial is for patients with advanced cervical cancer (stages IB2, II, IIIB, or IVA) that has spread to lymph nodes. Participants must have adequate blood counts and organ function, no severe allergies to cisplatin or immunotherapy drugs like atezolizumab, not be breastfeeding, and able to consent. HIV-positive patients can join if well-managed. Exclusions include prior pelvic radiation or systemic anticancer therapy within 3 years and certain health conditions.

Inclusion Criteria

My hemoglobin level is at least 8 g/dL.

International normalized ratio (INR) and activated partial thromboplastin time (aPTT) =< 1.5 x ULN

Platelets >= 100,000/mcL (> 50,000 for patients with hematologic malignancies)

Exclusion Criteria

I have not received a live vaccine in the last 4 weeks and do not plan to during the study.

I have a history of lung scarring or inflammation.

I haven't had major surgery in the last 28 days and don't expect to need one during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immune Priming

Participants receive atezolizumab as an immune primer before chemoradiotherapy

3 weeks

3 visits (in-person)

Chemoradiotherapy

Participants receive standard of care cisplatin chemotherapy and radiation therapy

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

1 visit at 1 month, 1 visit at 3 months, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Brachytherapy
• Cisplatin
• Radiation Therapy

Trial Overview The study tests the effectiveness of atezolizumab when given before and/or alongside standard chemoradiotherapy in activating the immune system against cervical cancer. Atezolizumab is a monoclonal antibody designed to help the body's immune system detect and fight tumor cells.

How Is the Trial Designed?

Group I: Arm B (atezolizumab, standard cisplatin and radiation therapy) Experimental Treatment 4 Interventions

Patients receive atezolizumab IV over 30-60 minutes on days 0, 21, and 42 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care cisplatin chemotherapy, radiation therapy, and image guided brachytherapy as in Arm A.

Group II: Arm A (atezolizumab, standard cisplatin and radiation therapy) Experimental Treatment 4 Interventions

Patients receive atezolizumab IV over 30-60 minutes on days -21, 0, and 21 in the absence of disease progression or unacceptable toxicity. Patients also receive standard of care cisplatin chemotherapy IV over 90 minutes on days 0, 7, 14, 21, 28, and 35. Beginning on day 0, patients also receive standard of care radiation therapy once daily (Monday-Friday) for a total of 25 fractions with image guided brachytherapy beginning in week 4, 5, or at the end of radiation therapy.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

NRG Oncology

Collaborator

Trials

242

Recruited

105,000+

Published Research Related to This Trial

Intensity-modulated radiotherapy (IMRT) for cervical cancer has been shown to reduce gastrointestinal toxicity while allowing for higher doses of radiation to be targeted at tumors, improving treatment safety.

Individualized, image-guided brachytherapy enhances the precision of high-dose radiation delivery, adapting to the tumor's specific shape and size, which may lead to better tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy of Cervical Cancer. Vordermark, D.[2017]

Cisplatin is the primary systemic anti-cancer agent used in conjunction with radiation for locally advanced cervical cancer, but its overall effectiveness is limited.

Recent phase 3 trials show that adding bevacizumab to chemotherapy regimens (cisplatin/paclitaxel or paclitaxel/topotecan) significantly improves overall survival for patients with metastatic or recurrent cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in cervical cancer pharmacotherapies. Markman, M.[2015]

Chemotherapy combined with radiation therapy has significantly improved overall survival rates in patients with locally advanced cervical carcinoma, with weekly cisplatin (40 mg/m²) showing the best response compared to other combinations.

Despite the exploration of various other cytotoxic and biologic agents, no treatment has proven to be more effective than weekly cisplatin in conjunction with radiotherapy, which remains the standard therapy for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel chemotherapy approaches in chemoradiation protocols. González-Cortijo, L., Carballo, N., González-Martín, A., et al.[2008]

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]

The maximum-tolerated dose (MTD) of paclitaxel when combined with cisplatin and pelvic radiotherapy for cervical cancer patients was determined to be 50 mg/m2 per week, with diarrhea identified as the main dose-limiting toxicity.

In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating that this regimen could be an effective option for treating locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. Pignata, S., Frezza, P., Tramontana, S., et al.[2020]

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. 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 ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5538

Integrative analysis of VB10.16 and atezolizumab in ... Integrative analysis of VB10.16 and atezolizumab in advanced HPV16-positive cervical cancer: Linking biomarker insights to clinical outcomes.

6. jitc.bmj.com jitc.bmj.com/content/13/1/e010827

Safety and efficacy of the therapeutic DNA-based vaccine ... The therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with ...