Combination Therapy for Advanced Cervical Cancer

Recruiting at 3 trial locations

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 phase I/II trial tests the safety and effectiveness of receiving external beam radiation therapy (EBRT) and brachytherapy along with chemotherapy, consisting of cisplatin and paclitaxel, and immunotherapy, consisting of bevacizumab and pembrolizumab, for the treatment of patients with stage IVB cervical cancer. EBRT is type of radiation therapy that uses a machine to aim high-energy rays at the cancer from outside of the body. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. Bevacizumab is in a class of medications called antiangiogenic agents. It works by stopping the formation of blood vessels that bring oxygen and nutrients to tumor. This may slow the growth and spread of tumor. A monoclonal antibody, such as pembrolizumab, is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Giving EBRT and brachytherapy along with chemotherapy and immunotherapy may be a safe and effective way to treat patients with stage IVB cervical cancer.

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 the combination therapy for advanced cervical cancer safe?

Research shows that the combination of cisplatin and paclitaxel, often used with radiation therapy, has been evaluated for safety in cervical cancer and other conditions. These studies generally found the treatment to be safe, though they also assessed the maximum tolerated dose to manage potential side effects. ^{1 2 3 4 5}

What makes the combination therapy of Cisplatin and Paclitaxel unique for advanced cervical cancer?

The combination of Cisplatin and Paclitaxel is unique for advanced cervical cancer because it has shown higher response rates and improved survival compared to Cisplatin alone, although it is less convenient and more toxic than other combinations like Carboplatin and Paclitaxel. ^{6 7 8 9 10}

What data supports the effectiveness of this treatment for advanced cervical cancer?

Research shows that cisplatin and paclitaxel, when used together with radiation therapy, can be effective in treating advanced cervical cancer. Cisplatin has been shown to enhance the effects of radiation, leading to improved survival rates in patients with advanced cervical cancer. ^{2 3 11 12 13}

Who Is on the Research Team?

Dana M Chase

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.

I have not needed treatment for an autoimmune disease in the last 2 years.

Known psychiatric or substance abuse disorders

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]

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]

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]

Citations

1. United States 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. [2016]

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

Phase II trial of paclitaxel and cisplatin in metastatic and recurrent carcinoma of the uterine cervix. [2017]

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

A phase II randomized trial comparing radiotherapy with concurrent weekly cisplatin or weekly paclitaxel in patients with advanced cervical cancer. [2021]

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

The role of cisplatin in the management of advanced squamous cell cancer of the cervix. [2013]

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

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. [2020]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

A Multi-Center, Phase II Clinical Trial of Genexol(R) (Paclitaxel) and Cisplatin for Patients with Non-Small Cell Lung Cancer. [2015]

7. England 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. [2015]

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

Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. [2022]

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

Cetuximab, topotecan and cisplatin for the treatment of advanced cervical cancer: A phase II GINECO trial. [2022]

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

A comparison of cisplatin/paclitaxel and carboplatin/paclitaxel in stage IVB, recurrent or persistent cervical cancer. [2015]

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

Carboplatin and paclitaxel for advanced and recurrent cervical carcinoma: the British Columbia Cancer Agency experience. [2022]

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

Efficacy of concurrent single-agent chemotherapy using radiotherapy in patients with cervical cancer: a meta-analysis. [2020]

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

The role of paclitaxel in the management of patients with carcinoma of the cervix. [2015]