Pembrolizumab + Chemoradiotherapy for Cervical Cancer

Recruiting at 184 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must not be taking: Immunostimulatory agents, Steroids

Disqualifiers: Hysterectomy, Immunodeficiency, Autoimmune, 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

Compensation: Varies

Number of Visits: 3

1060 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like systemic immunostimulatory agents and chronic systemic steroid therapy are not allowed before starting the trial. It's best to discuss your specific medications with the study team.

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

Research shows that combining cisplatin-based chemotherapy with radiation therapy is effective for treating advanced cervical cancer. Additionally, Pembrolizumab is approved for certain cervical cancers, suggesting potential benefits when combined with chemoradiotherapy. ^{1 2 3 4 5}

Is the combination of Pembrolizumab and chemoradiotherapy safe for cervical cancer treatment?

The studies reviewed focus on the safety of cisplatin (a chemotherapy drug) combined with radiotherapy for cervical cancer, showing it is generally safe but can have side effects. However, they do not specifically address the safety of adding Pembrolizumab to this treatment. ^{1 4 6 7 8}

What makes the treatment of Pembrolizumab combined with chemoradiotherapy unique for cervical cancer?

This treatment is unique because it combines pembrolizumab, an immune therapy that helps the body's immune system attack cancer cells, with traditional chemoradiotherapy, which uses drugs and radiation to kill cancer cells. Pembrolizumab is specifically used for cervical cancer that expresses PD-L1, a protein that helps cancer cells hide from the immune system, making this combination potentially more effective for certain patients. ^{3 9 10 11 12}

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab plus concurrent chemoradiotherapy compared to placebo plus concurrent chemoradiotherapy in participants with locally advanced cervical cancer. The primary hypotheses are that pembrolizumab plus concurrent chemoradiotherapy is superior to placebo plus concurrent chemoradiotherapy with respect to progression-free survival and overall survival. Once the study objectives have been met or the study has ended, participants will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for women with high-risk locally advanced cervical cancer stages IB2-IIB (node-positive) or III-IVA. They must have certain types of cervical cancer, not have had previous treatments for it, and be immunotherapy-naïve. Participants should be in good health overall, not pregnant or breastfeeding, willing to use contraception, and able to provide a tissue sample.

Inclusion Criteria

My organs are functioning well enough for treatment.

I am fully active or restricted in physically strenuous activity but can do light work.

My cancer can be seen and measured on scans.

Exclusion Criteria

Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results, and in the judgment of the investigator or Sponsor, would make the participant inappropriate for entry into this study

I cannot take cisplatin due to health reasons.

Has severe hypersensitivity to pembrolizumab and/or any of its excipients

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiotherapy

Participants receive concurrent chemoradiotherapy with either pembrolizumab or placebo

5-6 weeks

Weekly visits for chemoradiotherapy

Pembrolizumab/Placebo Treatment

Participants receive pembrolizumab or placebo every 3 weeks for 5 cycles, followed by every 6 weeks for 15 cycles

Up to 46 months

Every 3 weeks for 5 cycles, then every 6 weeks for 15 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 46 months

Extension Study

Participants may be enrolled in an extension study to continue protocol-defined assessments and treatment

Treatment Details

Interventions

• Brachytherapy
• Cisplatin
• External Beam Radiotherapy (EBRT)
• Pembrolizumab

Trial Overview The study tests if adding pembrolizumab (an immunotherapy drug) to standard chemoradiotherapy improves survival compared to using a placebo with the same chemotherapy and radiation treatment in patients with advanced cervical cancer. The main goal is seeing if the disease progresses more slowly or people live longer with pembrolizumab.

Participant Groups

Group I: chemoradiotherapy + placebo for pembrolizumab Experimental Treatment 4 Interventions

Participants receive placebo for pembrolizumab IV on Day 1 of each 3-week cycle (Q3W) for 5 cycles followed by placebo IV on Day 1 of each 6-week cycle (Q6W) for an additional 15 cycles. During the Q3W dosing period of placebo, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m\^2 IV once per week (QW) for 5 or 6 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units (Gy) for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days (with an extension to a maximum of 56 days for unforeseen delays).

Group II: chemoradiotherapy + pembrolizumab Experimental Treatment 4 Interventions

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for 5 cycles followed by pembrolizumab 400 mg IV on Day 1 of each 6-week cycle (Q6W) for an additional 15 cycles. During the Q3W dosing period of pembrolizumab, participants receive concurrent chemoradiotherapy. The standard of care chemoradiotherapy regimen includes cisplatin 40 mg/m\^2 IV once per week (QW) for 5 or 6 weeks plus external beam radiotherapy (EBRT) followed by brachytherapy with minimum total radiotherapy dose of 80 Gray Units (Gy) for volume-directed and 75 Gy for point-directed given with the total duration of radiation treatment not to exceed 50 days (with an extension to a maximum of 56 days for unforeseen delays).

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

GOG Foundation

Collaborator

Trials

48

Recruited

18,500+

European Network of Gynaecological Oncological Trial Groups (ENGOT)

Collaborator

Trials

41

Recruited

19,200+

Gynecologic Oncology Group

Collaborator

Trials

251

Recruited

65,400+

European Network for Gynaecological Oncological Trial Groups

Collaborator

Trials

4

Recruited

2,900+

Findings from Research

Volume-based high-dose-rate (HDR) brachytherapy (HDRVOL) plans significantly reduce radiation exposure to organs at risk (OAR) by 6-12% compared to traditional Point A (HDRPointA) plans, indicating a safer treatment approach for patients with locally advanced cervical cancer.

HDRVOL planning also improves the conformal index by 18-31%, demonstrating its efficacy in creating more precise radiation delivery to the target area while minimizing damage to surrounding healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of Point A and volume-based high-dose-rate plans: a single institution study on adaptive brachytherapy planning for cervical cancer. Paul, AG., Nalichowski, A., Abrams, J., et al.[2022]

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]

In a phase II study involving 27 patients with locally advanced or recurrent cervical carcinoma, the combination of cisplatin and Taxol chemotherapy with radiotherapy resulted in a complete clinical response in all patients, indicating high efficacy of this treatment approach.

The treatment was generally well tolerated, although some patients experienced significant side effects such as grade 3-4 neutropenia and grade 3 anemia, suggesting that while effective, careful monitoring for toxicity is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer. Miglietta, L., Franzone, P., Centurioni, MG., et al.[2015]

In a study of 77 patients with locally advanced cervical cancer, treatment with cisplatin, external beam radiotherapy, and two 9-Gy HDR brachytherapy insertions resulted in a 5-year progression-free survival rate of 75%, indicating effective disease control.

The treatment was associated with manageable side effects, with 47% of patients experiencing grade 3/4 gastrointestinal symptoms, but only 6% experiencing significant late toxicities, suggesting a favorable safety profile for this HDR brachytherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of concomitant cisplatin with external beam pelvic radiotherapy and two high-dose-rate brachytherapy insertions for the treatment of locally advanced cervical cancer. Novetsky, AP., Einstein, MH., Goldberg, GL., et al.[2022]

Pembrolizumab is an FDA-approved immune checkpoint inhibitor specifically targeting the PD-1 receptor, showing promise in treating recurrent or metastatic cervical cancer in patients whose tumors express PD-L1.

Clinical studies suggest that pembrolizumab could become a preferred treatment option for advanced cervical cancer, but further research is needed to identify which patients will benefit the most from this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for advanced cervical cancer: safety and efficacy. De Felice, F., Giudice, E., Bolomini, G., et al.[2021]

In a study of 11 heavily pretreated patients with recurrent cervical cancer, pembrolizumab demonstrated a clinical benefit rate of 36%, with 18% of patients showing a partial response and another 18% achieving disease stabilization.

The treatment was generally well tolerated, with a median overall survival of 26 weeks and a 6-month survival rate of 65%, indicating promising efficacy and manageable safety in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. Kranawetter, M., Röhrich, S., Müllauer, L., et al.[2019]

In a phase 3 trial involving 548 patients with PD-L1-positive metastatic cervical cancer, adding pembrolizumab to chemotherapy significantly improved progression-free survival, with a median of 10.4 months compared to 8.2 months for the placebo group.

Overall survival at 24 months was also better in the pembrolizumab group (53.0%) compared to the placebo group (41.7%), indicating that pembrolizumab enhances the effectiveness of chemotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. Colombo, N., Dubot, C., Lorusso, D., 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]

References

1. Cyprus pubmed.ncbi.nlm.nih.gov

Cisplatin monotherapy with concurrent radiotherapy versus combination of cisplatin and 5-fluorouracil chemotherapy with concurrent radiotherapy in patients with locoregionally advanced cervical carcinoma. [2013]

2. Poland pubmed.ncbi.nlm.nih.gov

Dosimetric evaluation of Point A and volume-based high-dose-rate plans: a single institution study on adaptive brachytherapy planning for cervical cancer. [2022]

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

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

4. Iran pubmed.ncbi.nlm.nih.gov

Concurrent Chemoradiotherapy without Brachytherapy in Locally Advanced Cervical Cancer. [2021]

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

A phase II trial with cisplatin-paclitaxel cytotoxic treatment and concurrent external and endocavitary radiation therapy in locally advanced or recurrent cervical cancer. [2015]

6. 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]

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

Efficacy and toxicity of concomitant cisplatin with external beam pelvic radiotherapy and two high-dose-rate brachytherapy insertions for the treatment of locally advanced cervical cancer. [2022]

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

Phase I study of daily cisplatin and concurrent radiotherapy in patients with cervical carcinoma. [2013]

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

Pembrolizumab for advanced cervical cancer: safety and efficacy. [2021]

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

Activity of Pembrolizumab in Recurrent Cervical Cancer: Case Series and Review of Published Data. [2019]

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

Pembrolizumab for Persistent, Recurrent, or Metastatic Cervical Cancer. [2023]

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

Pembrolizumab OK'd for Cervical Cancer. [2019]