Combination Therapy for Advanced Cervical Cancer

Recruiting at 3 trial locations

Overseen By Jenny Lester

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Jonsson Comprehensive Cancer Center

Must be taking: Antivirals

Must not be taking: Immunosuppressants, Steroids

Disqualifiers: Immunodeficiency, Active infection, Autoimmune, others

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

Compensation: Varies

Number of Visits: 31

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of treatments can safely and effectively treat stage IVB cervical cancer. It combines two types of radiation therapy, chemotherapy with cisplatin and paclitaxel, and immunotherapy with bevacizumab and pembrolizumab. The goal is to assess whether these combined treatments can more effectively target and kill cancer cells. Individuals diagnosed with stage IVB cervical cancer who have not yet started treatment might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, it focuses on understanding how the treatment works in participants and measuring its effectiveness in an initial group, offering a chance to contribute to groundbreaking research.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on antiretroviral treatment for HIV, you must continue it throughout the study. 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?

Previous studies have examined using a combination of drugs like pembrolizumab, cisplatin, paclitaxel, and bevacizumab to treat cervical cancer. The KEYNOTE-826 trial found that adding pembrolizumab to chemotherapy, with or without bevacizumab, extended the time patients lived without their cancer worsening.

Regarding safety, patients generally tolerated these treatments well. Most side effects were manageable and similar to those typically seen with these drugs. While side effects can occur, they usually do not require stopping treatment. Patients experienced tiredness, nausea, and changes in blood cell counts, which are common with cancer treatments.

Since this trial is in an early phase, it primarily focuses on safety. Evidence from past studies suggests that these treatments are generally safe for patients, even those with advanced cervical cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for advanced cervical cancer, which typically involve combinations of surgery, radiation, and chemotherapy, this investigational combination therapy introduces a unique blend of chemotherapy and immunotherapy. Researchers are excited because the addition of pembrolizumab, an immunotherapy drug, targets the cancer cells more precisely by boosting the immune system's ability to recognize and destroy them. Bevacizumab, another key component, helps inhibit the growth of new blood vessels that tumors need to grow, potentially enhancing the effectiveness of the therapy. Together, these features could offer a more targeted and robust approach to treating advanced cervical cancer compared to existing options.

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

In this trial, participants will receive a combination treatment that includes pembrolizumab, chemotherapy, and sometimes bevacizumab. Research has shown that this approach can help patients with advanced cervical cancer live longer. Pembrolizumab targets a specific protein called PD-L1, enhancing the immune system's ability to fight the cancer. Bevacizumab prevents the cancer from growing new blood vessels necessary for its survival. Paclitaxel and cisplatin, the chemotherapy drugs, work by killing or slowing the growth of cancer cells. This combination treatment has extended patients' lives more effectively than chemotherapy alone. ^{1 2 3 5 6}

Who Is on the Research Team?

Dana M Chase, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with advanced stage IVB cervical cancer. Participants should be eligible to receive radiation, chemotherapy with cisplatin and paclitaxel, and immunotherapy drugs like bevacizumab and pembrolizumab. Specific eligibility criteria are not provided but typically include factors such as age, overall health status, and previous treatments.

Inclusion Criteria

Archival tumor tissue sample or newly obtained biopsy provided

My cancer has a PD-L1 score higher than 1.

I am 18 or older with a confirmed diagnosis of advanced cervical cancer.

Exclusion Criteria

I have had radiation therapy for cervical cancer.

Known psychiatric or substance abuse disorders

Pregnant, breastfeeding, expecting to conceive, or father children within the study duration

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy and Immunotherapy

Participants receive cisplatin, paclitaxel, pembrolizumab, and bevacizumab intravenously on day 1 of each cycle. Cycles repeat every 21 days for 6 cycles.

18 weeks

6 visits (in-person)

Radiation Therapy

Participants undergo external beam radiation therapy (EBRT) for 25 treatments over 5 weeks and brachytherapy over 3-5 treatments.

5 weeks

25 visits (in-person)

Extended Immunotherapy

Participants receive pembrolizumab and bevacizumab every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs at 30 days, every 6 weeks for up to 1 year, then every 9 weeks.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Bevacizumab
• Brachytherapy
• Cisplatin
• External Beam Radiation Therapy
• Paclitaxel
• Pembrolizumab

Trial Overview The study tests the combination of external beam radiation therapy (EBRT) & brachytherapy with chemotherapy (cisplatin & paclitaxel) plus immunotherapy drugs (bevacizumab & pembrolizumab). It aims to assess if this treatment can safely improve outcomes in stage IVB cervical cancer patients.

How Is the Trial Designed?

Group I: Treatment (EBRT, brachytherapy, chemotherapy, immunotherapy) Experimental Treatment 8 Interventions

PART 1: Patients receive cisplatin IV, paclitaxel IV, pembrolizumab IV over 30 minutes, and bevacizumab IV on day 1 of each cycle. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients receive no treatment for 3 weeks. PART 2: Patients undergo EBRT for 25 treatments delivered over 5 weeks, and brachytherapy over 3-5 treatments. Patients also receive pembrolizumab IV over 30 minutes and bevacizumab IV on day 1 of each cycle. Cycles for immunotherapy repeat every 21 days for a total of 2 years in the absence of disease progression or unacceptable toxicity. Participants who complete study intervention after 2 years of pembrolizumab are eligible for up to 1 year of additional pembrolizumab (second course) upon experiencing disease progression. Patients undergo CT, PET/CT, and/or MRI throughout the study. Patients also undergo blood sample collection throughout the study.

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?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Merck Sharp & Dohme LLC

Industry 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

Published Research Related to This Trial

In a multicenter phase II trial involving 68 patients with locally advanced cervical cancer, concurrent chemoradiotherapy (CCRT) using weekly cisplatin and paclitaxel resulted in a high complete response rate of 76.5%.

The treatment demonstrated favorable long-term outcomes, with 2-year progression-free survival at 83.8% and overall survival at 92.7%, while maintaining manageable safety profiles with a 25% rate of late complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of concurrent chemoradiotherapy with weekly cisplatin and paclitaxel in patients with locally advanced uterine cervical cancer: The JACCRO GY-01 trial. Umayahara, K., Takekuma, M., Hirashima, Y., et al.[2016]

In a phase I trial involving 21 patients with locally advanced cervical cancer, the maximum tolerated dose (MTD) of weekly paclitaxel in combination with cisplatin was determined to be 40 mg/m², indicating a safe dosage for further studies.

The combination of weekly paclitaxel and cisplatin alongside radiation therapy was feasible and showed an acceptable toxicity profile, with significant side effects like grade 3 proctitis and vaginitis occurring at higher doses of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix. Prasad, E., Viswanathan, PN., Rangad, VF., et al.[2015]

Carboplatin-paclitaxel is an effective treatment for advanced or recurrent cervical cancer, showing a 20% partial response and 20% complete response rate in a study of 25 women, with a median overall survival of 21 months.

The treatment was well tolerated, with 84% of doses delivered on time and 96% at full dose, although common toxicities included anemia and neutropenia, highlighting the need for monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. Tinker, AV., Bhagat, K., Swenerton, KD., et al.[2022]

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]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2824%2904033-X/fulltext

final analysis according to bevacizumab use in the ... In KEYNOTE-826 (NCT03635567), pembrolizumab plus chemotherapy (±bevacizumab) significantly improved overall survival (OS) and progression-free ...

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

Pembrolizumab for Persistent, Recurrent, or Metastatic ... Pembrolizumab has efficacy in programmed death ligand 1 (PD-L1)–positive metastatic or unresectable cervical cancer that has progressed during chemotherapy.

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. keytruda.com keytruda.com/cervical-cancer/combination-therapy-clinical-trial-results/

RESULTS FOR KEYTRUDA + combination therapy KEYTRUDA + combination therapy for advanced cervical cancer was shown to help people live longer compared to combination therapy alone.

5. keytrudahcp.com keytrudahcp.com/efficacy/cervical-cancer-first-line-combination-therapy/

KEYNOTE-826 - Clinical Trial Results | HCP - Keytruda Health care professionals may find clinical trial results for first-line combination therapy for advanced cervical cancer in KEYNOTE-826.

6. 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 ...