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

22 Participants Needed

Trial Summary

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.

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

Research shows that combining cisplatin (a chemotherapy drug) with radiation therapy improves survival rates in cervical cancer patients. Intensity-modulated radiotherapy (IMRT) can reduce side effects and increase the effectiveness of the radiation dose. ^{1 2 3 4 5}

Is the combination of vaccine, cisplatin, and radiation therapy generally safe for humans?

Studies show that combining cisplatin with radiation therapy for cervical cancer is generally safe, with common side effects including nausea, vomiting, and anemia (low red blood cell count). Advanced radiation techniques like intensity-modulated radiation therapy (IMRT) may help reduce some side effects by sparing healthy tissues. ^{2 6 7 8 9}

What makes the Vaccine + Chemoradiation treatment for cervical cancer unique?

This treatment combines a vaccine with chemoradiation, which is not a standard approach for cervical cancer. It uses cisplatin (a chemotherapy drug) and advanced radiation techniques like IMRT and IGRT to potentially improve tumor control and reduce side effects compared to traditional methods. ^{1 2 4 6 10}

What is the purpose of this trial?

This phase IIA trial studies the effect of a vaccine (PDS0101) when given together with chemotherapy and radiation therapy (chemoradiation) in treating patients with stage IB3-IVA cervical cancer. Chemotherapy drugs, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. PDS0101 is a type of vaccine that is intended to help the immune system respond to human papillomavirus (HPV16)-infected cervical tumor cells. PDS0101 contains two active components: the first is called R-DOTAP (Versamune) and is included in the vaccine to boost the immune system's response against the HPV viral proteins and the second group of active components are selected small pieces of proteins (called peptides) taken from the HPV virus. Giving PDS0101 in combination with chemoradiation may work help to control cervical cancer.

Research Team

Ann H. Klopp

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Radiotherapy of Cervical Cancer. [2017]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Concurrent weekly single cisplatin vs triweekly cisplatin alone with radiotherapy for treatment of locally advanced cervical cancer: a meta-analysis. [2020]

3. 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]

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

Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy in the treatment of locally advanced cervical carcinoma: An updated meta-analysis based on randomized controlled trials. [2022]

5. Singapore pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. [2020]

6. England 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. [2023]

7. Poland pubmed.ncbi.nlm.nih.gov

Image guided radiation therapy boost in combination with high-dose-rate intracavitary brachytherapy for the treatment of cervical cancer. [2022]

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

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. [2013]

9. India pubmed.ncbi.nlm.nih.gov

A randomized study for dosimetric assessment and clinical impact of bone marrow sparing intensity-modulated radiation therapy versus 3-dimensional conformal radiation therapy on hematological and gastrointestinal toxicities in cervical cancer. [2022]

10. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Induction chemotherapy for locally advanced cervical cancer]. [2015]