Atezolizumab + Chemoradiotherapy for Cervical Cancer

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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies how well atezolizumab before and/or with standard of care chemoradiotherapy works in immune system activation in patients with stage IB2, II, IIIB, or IVA cervical cancer that has spread to the lymph nodes. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving atezolizumab before and/or with chemoradiotherapy may lower the chance of tumors growing or spreading.

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.

What data supports the effectiveness of the treatment Atezolizumab + Chemoradiotherapy for Cervical Cancer?

Research shows that combining chemotherapy with radiotherapy, particularly using cisplatin, improves survival rates in cervical cancer compared to radiotherapy alone. Additionally, intensity-modulated radiotherapy (IMRT) can reduce side effects and improve treatment precision. ^{1 2 3 4 5}

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

The combination of Atezolizumab with other treatments like bevacizumab has been studied for safety in advanced cervical cancer, and chemoradiotherapy with cisplatin is a standard treatment with known safety profiles. Intensity-modulated radiation therapy (IMRT) can reduce side effects like gastrointestinal issues, and cisplatin is generally well-tolerated when used with radiotherapy. ^{1 2 6 7 8}

How is the treatment Atezolizumab + Chemoradiotherapy for Cervical Cancer different from other treatments?

This treatment combines Atezolizumab, an immunotherapy drug that helps the immune system fight cancer, with chemoradiotherapy, which is the standard treatment for cervical cancer. The addition of Atezolizumab is novel as it may enhance the effectiveness of the existing chemoradiotherapy regimen by boosting the body's immune response against the cancer. ^{1 2 4 9 10}

Research Team

Jyoti S Mayadev

Principal Investigator

NRG Oncology

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Radiotherapy of Cervical Cancer. [2017]

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

Novel chemotherapy approaches in chemoradiation protocols. [2008]

3. England pubmed.ncbi.nlm.nih.gov

A systematic overview of radiation therapy effects in cervical cancer (cervix uteri). [2019]

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

Advances in cervical cancer pharmacotherapies. [2015]

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

The MITO CERV-2 trial: A randomized phase II study of cetuximab plus carboplatin and paclitaxel, in advanced or recurrent cervical cancer. [2019]

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

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

7. England pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. [2020]

8. India pubmed.ncbi.nlm.nih.gov

A randomized study for dosimetric assessment and clinical impact of bone marrow sparing intensity-modulated radiation therapy versus 3-dimensional conformal radiation therapy on hematological and gastrointestinal toxicities in cervical cancer. [2022]

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

Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer. [2022]

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

Capecitabine-based chemoradiotherapy with adjuvant capecitabine for locally advanced squamous carcinoma of the uterine cervix: phase II results. [2015]