Vaccine + Chemoradiation for Cervical Cancer

Overseen By Ann H. Klopp

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Immunotherapy, Steroids

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 35

Duration: 5-7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of a new vaccine, PDS0101 (Liposomal HPV-16 E6/E7 Multipeptide Vaccine), when combined with chemotherapy and radiation therapy for treating cervical cancer. The goal is to determine if adding the vaccine can enhance the immune system's ability to combat HPV-linked cervical cancer. This trial targets individuals with newly diagnosed advanced cervical cancer, specifically those with tumors 5 cm or larger or cancer that has spread to nearby lymph nodes. Participants will receive radiation and chemotherapy, along with the vaccine, over several weeks. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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, you cannot participate if you have used certain immunotherapies or immunosuppressive therapies recently, so it's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that cisplatin, a chemotherapy drug used in the trial, is generally well-tolerated. One study found that 49.4% to 80% of women completed at least six weekly cycles of cisplatin when combined with radiation therapy. Another study found that combining cisplatin with S-1 was safe for patients with advanced cervical cancer.

For the vaccine PDS0101, early results suggest it is safe. In a study with fourteen patients who had advanced HPV-related cancers, including cervical cancer, the vaccine was used without major safety issues. This vaccine is designed to help the immune system fight cervical cancer cells infected with HPV.

Overall, both cisplatin and PDS0101 appear well-tolerated based on previous research. These findings offer some reassurance about the safety of these treatments in the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of the PDS0101 vaccine with standard chemoradiation treatments like cisplatin and radiation therapy for cervical cancer because it introduces an innovative approach to fighting the disease. While traditional treatments focus on destroying cancer cells directly, PDS0101 is designed to stimulate the body's immune system to specifically target and attack cancer cells, potentially enhancing the overall effectiveness of the treatment. This vaccine-driven immunotherapy approach could lead to improved outcomes by reducing the risk of cancer progression and recurrence, offering new hope for patients beyond the existing standard of care.

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

Research has shown that cisplatin, one of the treatments in this trial, is effective for cervical cancer, particularly when the total dose exceeds 200 mg. Studies have found that this dosage can improve survival rates in patients with advanced cancer.

Participants in this trial will also receive the vaccine PDS0101, designed to help the immune system target tumor cells infected with HPV16. Early results suggest that, when combined with other treatments, it can benefit patients with HPV-related cancers. This vaccine contains R-DOTAP, which enhances the immune response against the virus. Using PDS0101 alongside chemoradiation, which includes radiation therapy and cisplatin, may enhance the overall effectiveness of cervical cancer treatment. ^{2 6 7 8 9}

Who Is on the Research Team?

Ann H. Klopp

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with newly diagnosed stage IB3-IVA cervical cancer, specifically squamous cell carcinoma. Participants must have a tumor size of at least 5 cm or positive nodal disease and should not have other current malignancies except certain skin cancers. They need to be in good physical condition (ECOG 0-2) and have normal organ function tests. People with HIV, hepatitis B or C, serious infections, recent immunotherapy or steroid use, known allergies to the vaccine components, previous pelvic radiation or chemotherapy for cervical cancer are excluded.

Inclusion Criteria

Creatinine =< 1.5

Alkaline phosphatase (alk phos) =< 2-fold the upper limit of normal

Total bilirubin (total bili) =< 2-fold the upper limit of normal

Exclusion Criteria

I have had a therapeutic HPV vaccine, not just the preventive ones like Gardasil.

Serious concomitant disorder, including active systemic infection requiring treatment, as judged by the investigator

I have had hepatitis B or C but am cured of hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo radiation therapy 5 days per week for 5-7 weeks and receive cisplatin IV weekly, along with PDS0101 vaccine on specified days

5-7 weeks

5 visits per week (in-person) for radiation, weekly visits for chemotherapy

Follow-up

Participants are monitored for safety and effectiveness after treatment

18 months

Visits at 30 days, 1, 4, 6, 12, and 18 weeks, and 18 months

Long-term safety monitoring

Monitoring for chronic toxicity and long-term outcomes

From day 81 to completion of trial

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Liposomal HPV-16 E6/E7 Multipeptide Vaccine PDS0101
• Radiation Therapy

Trial Overview

The IMMUNOCERV trial is testing the combination of a new HPV-related vaccine called PDS0101 with standard chemoradiation therapy using cisplatin against advanced cervical cancer. The vaccine aims to boost the immune system's response against HPV-infected tumor cells by including specific protein pieces from the virus.

How Is the Trial Designed?

Group I: Treatment (radiation therapy, cisplatin, PDS0101) Experimental Treatment 3 Interventions

Patients undergo radiation therapy over 1 hour 5 days per week (Monday-Friday) for 5-7 weeks and receive cisplatin IV over 4 hours QW during the 5 weeks of radiation therapy in the absence of disease progression and unacceptable toxicity. Patients also receive PDS0101 SC on days -10, 7, 28, 49, and 170 in the absence of disease progression or unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Intensity-modulated radiotherapy (IMRT) for cervical cancer has been shown to reduce gastrointestinal toxicity while allowing for higher doses of radiation to be targeted at tumors, improving treatment safety.

Individualized, image-guided brachytherapy enhances the precision of high-dose radiation delivery, adapting to the tumor's specific shape and size, which may lead to better tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy of Cervical Cancer. Vordermark, D.[2017]

In a study of 271 patients with high-risk cervical cancer, sequential treatment with paclitaxel and carboplatin followed by radiation showed a 5-year survival rate of 85.8%, compared to 78.9% for simultaneous cisplatin-based radiochemotherapy, although the difference was not statistically significant (P = 0.25).

The sequential treatment resulted in lower rates of severe hematological toxicity and early treatment termination compared to the simultaneous approach, suggesting it may be a safer alternative when immediate postoperative radiation is not feasible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase III adjuvant study in high-risk cervical cancer: simultaneous radiochemotherapy with cisplatin (S-RC) versus systemic paclitaxel and carboplatin followed by percutaneous radiation (PC-R): a NOGGO-AGO Intergroup Study. Sehouli, J., Runnebaum, IB., Fotopoulou, C., et al.[2023]

A study involving 10 patients with advanced cervical cancer evaluated the safety of combining cisplatin with radiation therapy, finding that most adverse effects were mild (grade 2 or less), with nausea/vomiting being the most common issue.

Despite some cases of anemia being noted as a serious concern, the overall toxicity of the treatment was deemed acceptable, suggesting that larger studies can be conducted to further assess the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. Suggs, CL., Lee, JC., Lewis, GC., et al.[2013]

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 involving 42 cervical cancer patients, combining image-guided radiation therapy (IGRT) with high-dose-rate intracavitary brachytherapy (ICBT) improved the dose distribution to the tumor while reducing exposure to surrounding healthy tissues, such as the bladder and rectum.

The results showed that while the target dose to the high-risk clinical target volume (HRCTV) was similar between the combined treatment and optimized ICBT alone, the combined approach significantly increased the dose to intermediate-risk areas and decreased the dose to critical organs, suggesting a safer and more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer. Wang, X., Li, J., Wang, P., et al.[2022]

The combination of weekly paclitaxel and cisplatin during radiation therapy shows promising efficacy in 'high-risk' cervical cancer patients, with an overall survival rate of 68% at a median follow-up of 58 months.

While hematologic toxicity was common, it was manageable and did not frequently cause treatment delays; however, significant late complications occurred in 52% of patients, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. Argenta, PA., Ghebre, R., Dusenbery, KE., et al.[2020]

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