Chemotherapy + Bevacizumab + Atezolizumab for Cervical Cancer

(BEATcc Trial)

Not currently recruiting at 83 trial locations

Overseen By Carmen Marqués, MD

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Grupo Español de Investigación en Cáncer de Ovario

Must not be taking: Anti-VEGF, Anti-PD1, Anti-PDL1, Anti-CTLA4

Disqualifiers: Brain metastases, Autoimmune disease, Cardiovascular disease, Active infections, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: 18 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding the drug atezolizumab (Tecentriq, an immunotherapy) to the usual chemotherapy and bevacizumab (Avastin) can improve survival for women with advanced cervical cancer that has recurred or spread. The goal is to determine if this new combination outperforms the current standard treatment. Women diagnosed with stage IVB, persistent, or recurrent cervical cancer who have not received prior systemic therapy for these conditions may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like systemic immunosuppressive agents and therapeutic anticoagulants must be stopped before starting the trial. It's best to discuss your specific medications with the trial team.

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

Research has shown that a combination of the drugs atezolizumab, bevacizumab, and chemotherapy has been tested in patients with advanced cervical cancer. In these studies, researchers noted some safety concerns. About 79% of the patients reported serious side effects, indicating that many experienced significant issues.

Despite the seriousness of these side effects, the trial's phase three status suggests that earlier studies found the treatment to be somewhat safe for humans. In this phase, researchers assess both the treatment's effectiveness and its safety in larger groups.

The treatment includes atezolizumab, a drug already approved for other conditions, which provides some reassurance about its safety since it is not entirely new. However, potential serious side effects should be considered and discussed with healthcare providers when contemplating trial participation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining atezolizumab with the standard chemotherapy and bevacizumab for cervical cancer because it introduces an innovative approach to treatment. Atezolizumab is an immunotherapy that targets PD-L1, a protein that helps cancer cells evade the immune system. By adding this to the mix, the treatment aims to enhance the body's immune response against cancer. Unlike traditional chemotherapy alone, which targets and kills rapidly dividing cells, this combination has the potential to boost immune activity while simultaneously attacking the cancer, offering a dual mechanism that could improve outcomes for patients.

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

In this trial, participants will join different treatment arms to evaluate the effectiveness of combining atezolizumab with bevacizumab and chemotherapy for cervical cancer. Research has shown that adding atezolizumab to the treatment regimen can extend the lives of cervical cancer patients. One study found that this addition increased survival time to an average of 32.1 months, compared to 22.8 months with the usual treatment. This combination works by helping the immune system find and attack cancer cells. Bevacizumab also aids by cutting off the blood supply to tumors, making it harder for the cancer to grow. This approach has shown promise in treating advanced cervical cancer. ^{1 2 4 5 6}

Who Is on the Research Team?

Ana Oaknin

Principal Investigator

Vall d´Hebron University Hospital

Are You a Good Fit for This Trial?

This trial is for women over 18 with advanced cervical cancer that can't be cured by surgery or radiation. They should not have had previous systemic therapy for their condition, must be able to follow the study plan, and have a life expectancy of at least 3 months. Participants need good organ function and blood counts, no serious allergies to the drugs being tested, and agree to use effective contraception.

Inclusion Criteria

You are able to follow the study rules, as determined by the person in charge of the study.

Adequate coagulation (PTT, PT/INR within acceptable range)

My blood tests show my organs are working well.

Exclusion Criteria

My kidney swelling hasn't improved with specific treatments.

My condition can be treated with the goal of curing it.

My cancer is at Stage IVA and cannot be treated with chemo and radiation at the same time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive platinum chemotherapy plus paclitaxel with bevacizumab and atezolizumab or platinum chemotherapy plus paclitaxel and bevacizumab

18 weeks

Every 3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

Open-label extension (optional)

Participants may continue on biologic therapy, namely bevacizumab or bevacizumab plus atezolizumab, upon achieving a complete response after ≥6 treatment cycles

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Cisplatin/Carboplatin
• Paclitaxel

Trial Overview The trial tests if adding Atezolizumab (anti-PD-L1) improves survival when combined with standard chemotherapy (Cisplatin/Carboplatin and Paclitaxel) plus Bevacizumab in stage IVB cervical cancer. It's an open-label phase III study where patients are randomly assigned to two groups without selection based on PD-L1 expression.

How Is the Trial Designed?

Group I: Arm B Experimental Treatment 4 Interventions

cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2 + bevacizumab 15mg/kg + atezolizumab 1200mg i.v, D1 Q3W.Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologics therapy, namely bevacizumab plus atezolizumab, upon investigator discussion.

Group II: Arm A Active Control 3 Interventions

Cisplatin 50mg/m2 or carboplatin AUC 5 + paclitaxel 175mg/m2+ bevacizumab 15mg/kg i.v D1 Q3W. Patients who achieve a complete response after ≥6 treatment cycles may be allowed to continue only on biologic therapy, namely bevacizumab, upon investigator discussion.

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?

Grupo Español de Investigación en Cáncer de Ovario

Lead Sponsor

Trials

21

Recruited

5,200+

Gynecologic Oncology Group Foundation

Collaborator

Trials

3

Recruited

1,300+

AGO Study Group

Collaborator

Trials

31

Recruited

15,800+

Apices Soluciones S.L.

Industry Sponsor

Trials

41

Recruited

3,600+

Hoffmann-La Roche

Industry Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

ARCAGY/ GINECO GROUP

Collaborator

Trials

65

Recruited

16,600+

Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies

Collaborator

Trials

3

Recruited

1,700+

MaNGO

Collaborator

Trials

2

Recruited

830+

NSGO

Collaborator

Trials

2

Recruited

1,400+

Japanese Gynecologic Oncology Group

Collaborator

Trials

4

Recruited

2,100+

Published Research Related to This Trial

Cemiplimab, administered as monotherapy or in combination with hypofractionated radiation therapy, showed a 10% objective response rate in patients with recurrent or metastatic cervical cancer, particularly in those with squamous histology, indicating its potential efficacy in this subgroup.

The most common side effects were diarrhea, fatigue, and hypokalemia, affecting 35%, 25%, and 25% of patients respectively, suggesting that while cemiplimab has anti-tumor activity, it also has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PD-1 blockade in recurrent or metastatic cervical cancer: Data from cemiplimab phase I expansion cohorts and characterization of PD-L1 expression in cervical cancer. Rischin, D., Gil-Martin, M., González-Martin, A., et al.[2021]

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 combination of paclitaxel, carboplatin, and bevacizumab showed a high objective response rate of 88% in 34 patients with advanced or recurrent cervical cancer, indicating strong efficacy in this difficult-to-treat population.

While the treatment was effective, it was associated with significant hematologic toxicities, including neutropenia and leukopenia in 41.2% of patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer. Suzuki, K., Nagao, S., Shibutani, T., et al.[2019]

Citations

1. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(23)02405-4/abstract

a randomised, open-label, phase 3 trial Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11631890/

Atezolizumab plus bevacizumab and chemotherapy as first ... The present study evaluated the cost-effectiveness of adding atezolizumab to standard therapy (atezolizumab plus bevacizumab [BC]) for metastatic, persistent, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1048891X2400344X

A randomized phase III trial of platinum chemotherapy plus ... The study aims to demonstrate that the combination with cisplatin-paclitaxel plus bevacizumab and atezolizumab is more effective in terms of overall survival ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03556839

Study Details | NCT03556839 | Platinum Chemotherapy ... The study is a randomized open label phase III trial to investigate the impact of atezolizumab in combination with bevacizumab and cisplatin or carboplatin / ...

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

Atezolizumab Efficacy in Cervical Cancer Consistent ... An interim OS analysis also showed a substantial benefit, with a median OS of 32.1 months (95% CI, 25.3-36.8) vs 22.8 months (95% CI, 20.3-28.0) ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673623024054

Atezolizumab plus bevacizumab and chemotherapy for ... Adding atezolizumab to a standard bevacizumab plus platinum regimen for metastatic, persistent, or recurrent cervical cancer significantly improves progression ...