Pembrolizumab + Chemotherapy for Cervical Cancer

Recruiting at 28 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunotherapy, Steroids

Disqualifiers: Prior therapy, Autoimmune, Cardiac, 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: 9

336 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether adding extra chemotherapy before the usual treatment can help fight cervical cancer that has spread to nearby tissues or lymph nodes. The usual treatment includes chemotherapy, radiation, and pembrolizumab, a drug that helps the immune system attack cancer. Participants will receive either the standard treatment or an additional round of chemotherapy with different drugs, such as carboplatin or cisplatin, to determine which is more effective. Those with newly diagnosed cervical cancer that has spread locally and who haven't had certain prior treatments may be suitable 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.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like immunotherapy, pelvic radiation, or systemic steroids above a certain dose. 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 the treatments in this trial have been studied before. Pembrolizumab, when combined with chemotherapy, has demonstrated benefits in other cervical cancer studies, such as extending patient survival.

Carboplatin and paclitaxel are common chemotherapy drugs. They are usually well-tolerated but can cause side effects like nausea and fatigue. Pembrolizumab is an immunotherapy drug that aids the immune system in fighting cancer. Some patients have reported fatigue or skin issues with this drug.

Cisplatin, another chemotherapy drug used in the trial, is similar to carboplatin but can sometimes cause more serious side effects, such as kidney problems or hearing loss. However, many people tolerate it well.

In summary, these treatments have been used before and are generally safe, though side effects can occur. Researchers will closely monitor the safety of the combination in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of pembrolizumab with chemotherapy for cervical cancer because it introduces an innovative approach by combining immunotherapy with traditional chemotherapy. Pembrolizumab is an immune checkpoint inhibitor that enhances the immune system's ability to target and destroy cancer cells, which is different from standard treatments that rely solely on chemotherapy or radiation. This combination aims to improve the effectiveness of treatment by tackling the cancer from multiple angles, potentially leading to better outcomes. Additionally, the structured maintenance phase with pembrolizumab may help in prolonging remission, offering hope for longer-lasting results compared to current standard care options.

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

Research shows that adding pembrolizumab to chemotherapy can help treat cervical cancer. In this trial, participants in Arm 2 will receive an induction phase with pembrolizumab and platinum-based chemotherapy, such as carboplatin. Studies have shown that this combination leads to better treatment results and longer survival for patients with advanced cervical cancer. Specifically, patients experienced a progression-free survival of 10.4 months compared to 8.2 months without pembrolizumab, indicating a slower disease progression. Paclitaxel, another component of the treatment in Arm 2, stops cancer cells from growing and dividing. Overall, this combination shows promise for improving outcomes in cervical cancer. ^{1 2 3 4 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 newly diagnosed cervical cancer that has spread locally but not to distant parts of the body. Eligible types include squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma. Patients must have certain stages (IIIA, IIIB, IIIC1/2 or IVA) without metastases above a specific spinal level and no prior full hysterectomy.

Inclusion Criteria

My cancer is stage IVA, and I have not had a hysterectomy.

My breast cancer is at stage IIIC2.

My cancer is stage IIIA (T3aN0M0).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive carboplatin and paclitaxel weekly for 3 weeks and pembrolizumab every 3 weeks for 2 cycles

6 weeks

Weekly visits for chemotherapy administration

Chemoradiation

Patients receive cisplatin weekly and pembrolizumab every 3 weeks, along with daily radiation therapy for 5 weeks followed by brachytherapy

7 weeks

Daily visits for radiation therapy, weekly visits for chemotherapy

Maintenance

Patients receive pembrolizumab every 6 weeks for up to 15 cycles

Approximately 90 weeks

Every 6 weeks for pembrolizumab administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Every 3 months for 2 years, then every 6 months for 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin
• Cisplatin
• Pembrolizumab

Trial Overview The study compares standard chemoradiation therapy with pembrolizumab maintenance against adding induction chemotherapy (carboplatin and paclitaxel) before this treatment in high-risk cervical cancer. It aims to see if starting with extra chemotherapy improves outcomes.

How Is the Trial Designed?

Group I: Arm 2 (induction and standard care) Experimental Treatment 12 Interventions

INDUCTION: Patients receive carboplatin IV and paclitaxel IV QW on weeks 1-3 and pembrolizumab IV over 30 minutes Q3W on week 1 for each cycle. Cycles repeat every 3 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. CHEMORADIATION: Patients receive cisplatin IV QW for 5 weeks and pembrolizumab IV over 30 minutes every Q3W for 5 doses. Patients also undergo radiation therapy with EBRT or IMRT once daily 5 days per week for 25-29 treatments in weeks 7-11 followed by brachytherapy up to twice per week for 4-5 treatments in weeks 11-13. Treatment is given in the absence of disease progression or unacceptable toxicity MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes Q6W for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan, CT scan, chest x-ray and/or MRI and blood sample collection throughout the study.

Group II: Arm 1 (Standard care) Active Control 10 Interventions

CHEMORADIATION: Patients receive cisplatin IV QW for 5 weeks and pembrolizumab IV over 30 minutes Q3W for 5 doses. Patients also undergo radiation therapy with EBRT or IMRT once daily 5 days per week for 25-29 treatments in weeks 1-5 followed by brachytherapy up to twice per week for 4-5 treatments in weeks 5-7. Treatment is given in the absence of disease progression or unacceptable toxicity MAINTENANCE: Patients receive pembrolizumab IV over 30 minutes Q6W for 14 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET scan, CT scan, chest x-ray and/or MRI and blood sample collection throughout the study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2112435

Pembrolizumab for Persistent, Recurrent, or Metastatic ... In 617 patients in the intention-to-treat population, progression-free survival was 10.4 months and 8.2 months, respectively (hazard ratio, 0.65 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11468096/

The outcome of advanced and recurrent cervical cancer ... First-line ICI plus platinum and paclitaxel yields better treatment responses, longer survival, and non-differential adverse events versus first-line platinum ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.5531

Added value of bevacizumab. | Journal of Clinical Oncology Background: Pembrolizumab (pembro) showed a statistical significant survival benefit in persistent, recurrent, or metastatic cervical cancer ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S092375342404033X

Pembrolizumab plus chemotherapy for advanced and ... Women with metastatic cervical cancer have a poor prognosis, with a 5-year overall survival (OS) rate of only 19%. Standard of care first-line treatment of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04238988

NCT04238988 | Carboplatin-Paclitaxel-Pembrolizumab in ... Patients with stage IB2-IIB cervical cancer will be treated with 3 cycles of neoadjuvant Carboplatin-Paclitaxel chemotherapy (Carboplatin AUC 5 d1 q 21+ ...

6. asco.org asco.org/abstracts-presentations/ABSTRACT399114

KEYNOTE-826: Final overall survival results from a ... Conclusions: The addition of pembro to chemo ± bev significantly reduced the risk of death by 40% in the PD-L1 CPS ≥1 population, by 37% in the all-comer ...