Chemotherapy + Bevacizumab + Atezolizumab for Cervical Cancer

(BEATcc Trial)

Recruiting at 71 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

410 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The study will integrate the efficacy of combining the anti programmed death-ligand 1 (anti-PD-L1) agent atezolizumab with the current standard of care in Stage IVB , persistent or recurrent carcinoma of the cervix, namely cisplatin or carboplatin/paclitaxel/bevacizumab. It will be explored the combination of bevacizumab plus atezolizumab, with no patient selection based on PD-L1 expression, allowing an all-comer assessment of atezolizumab activity. The study is a randomized open label phase III trial to investigate the impact of atezolizumab in combination with bevacizumab and cisplatin or carboplatin /paclitaxel chemotherapy on overall survival and will employ the intent to treat principle, and random assignment to one of the 2 arms will be balanced according to disease histology (squamous cell carcinoma vs adenocarcinoma), prior platinum therapy as a radiation sensitizer (no prior cis-Radiotherapy (RT) versus prior cis-RT) and chemotherapy backbone (cisplatin vs carboplatin). This trial will be run in an open label design due to the following considerations: the control arm is the standard of care for women diagnosed with metastatic, persistant or recurrent cervical cancer because of its impact on overall survival and the primary endpoint of the study is overall survival (OS), so blinding is not needed to ensure a robust assessment.

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 the combination of chemotherapy, bevacizumab, and atezolizumab safe for cervical cancer treatment?

Studies have shown that the combination of paclitaxel, carboplatin, and bevacizumab is generally safe for advanced cervical cancer, though it may have some side effects. Atezolizumab combined with bevacizumab has also been evaluated for safety in advanced cervical cancer, indicating it is generally safe for use in humans. ^{1 2 3 4 5}

How is the drug combination of Atezolizumab, Bevacizumab, Cisplatin/Carboplatin, and Paclitaxel unique for cervical cancer?

This drug combination is unique because it includes Atezolizumab, a PD-L1 antibody, which is being studied for its potential to enhance the effects of Bevacizumab and chemotherapy in advanced cervical cancer, offering a novel approach compared to traditional treatments. ^{3 6 7 8 9}

What data supports the effectiveness of the drug combination of chemotherapy, bevacizumab, and atezolizumab for cervical cancer?

Research shows that adding bevacizumab to chemotherapy (cisplatin-paclitaxel or carboplatin-paclitaxel) significantly improves survival in advanced cervical cancer. Additionally, a study reported the safety and effectiveness of combining atezolizumab with bevacizumab for advanced cervical cancer. ^{3 4 9 10 11}

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 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.

My kidney swelling hasn't improved with specific treatments.

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

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]

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]

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]

Citations

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

Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer. [2021]

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

Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer. [2019]

3. Greece pubmed.ncbi.nlm.nih.gov

Bevacizumab Efficacy and Recurrence Pattern of Persistent and Metastatic Cervical Cancer. [2023]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Bevacizumab in Metastatic, Recurrent, or Persistent Cervical Cancer: The BC Cancer Experience. [2019]

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

Paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy for metastatic, recurrent, and persistent uterine cervical cancer: An open-label multicenter phase II trial (JGOG1079). [2022]

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

Paclitaxel, Carboplatin, and Bevacizumab in Advanced Cervical Cancer: A Treatment Response and Safety Analysis. [2022]

8. United States 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. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Advances in cervical cancer pharmacotherapies. [2015]

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

Pharmacodynamics of current and emerging treatments for cervical cancer. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Cisplatin plus paclitaxel and bevacizumab versus carboplatin plus paclitaxel and bevacizumab for the first-line treatment of metastatic or recurrent cervical cancer. [2022]