Pembrolizumab + Chemotherapy + Radiation for Anal Cancer

Recruiting at 1 trial location

Overseen By Rebecca Mottier

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Dustin Deming

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Uncontrolled illness, Active CNS metastases, Autoimmune disease, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

A single arm phase II study of pembrolizumab, carboplatin, paclitaxel, and radiation for the treatment of early-stage anal cancer. There are 2 treatments phases and then surveillance. The first treatment phase is the chemoradiation phase (Cycle 1-6, weekly cycles) which is followed by the maintenance phase (Cycle 7-14, 6 week cycles).

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, if you are on a medication that is contraindicated (not allowed) with the study drugs, you may need to stop or switch to an alternative within 7 days before starting the trial.

What data supports the effectiveness of the treatment Pembrolizumab + Chemotherapy + Radiation for Anal Cancer?

Research shows that pembrolizumab, a drug that helps the immune system fight cancer, has been effective in treating advanced anal cancer and other cancers when combined with radiation. Studies also suggest that combining radiation with pembrolizumab can enhance the immune response against tumors. ^{1 2 3 4 5}

Is the combination of Pembrolizumab, Chemotherapy, and Radiation generally safe for humans?

Pembrolizumab, when used with chemotherapy and radiation, can cause immune-related side effects like pneumonitis (lung inflammation), glossitis (tongue inflammation), and thrombocytopenia (low platelet count), which can be serious. These side effects have been observed in treatments for various cancers, so it's important for doctors to monitor patients closely for these reactions. ^{6 7 8 9 10}

What makes the treatment of Pembrolizumab combined with chemotherapy and radiation unique for anal cancer?

This treatment is unique because it combines pembrolizumab, an immune therapy that helps the body's immune system fight cancer, with chemotherapy and radiation, which are standard treatments. This combination aims to enhance the overall effectiveness against anal cancer, especially when few other treatment options are available. ^{1 3 5 11 12}

Research Team

Dustin Deming, M.D.

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

This trial is for individuals with early-stage anal cancer. Participants should be suitable for chemotherapy and radiation, but specific inclusion and exclusion criteria details are not provided.

Inclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

2. Age ≥ 18 years at the time of consent.

3. ECOG Performance Status of 0-1 within 30 days prior to registration.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Participants receive a combination of pembrolizumab, carboplatin, paclitaxel, and radiation. Carboplatin and paclitaxel are administered weekly, and pembrolizumab is administered on cycles 1 and 4.

6 weeks

6 visits (in-person)

Maintenance

Participants receive pembrolizumab every 6 weeks for 8 cycles.

48 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment emergent toxicities and overall response rate.

3 years

Treatment Details

Interventions

• Carboplatin (Chemotherapy)
• Paclitaxel (Chemotherapy)
• Pembrolizumab (Checkpoint Inhibitor)
• Radiation (Radiation)

Trial Overview The study tests a combination of pembrolizumab (an immunotherapy drug), carboplatin, paclitaxel (chemotherapy drugs), and radiation therapy in two phases: chemoradiation followed by maintenance, to treat early-stage anal cancer.

Participant Groups

Group I: Pembrolizumab plus carbopltin and paclitaxel Experimental Treatment 4 Interventions

All patients in the chemoradiation phase will receive a combination of pembrolizumab, carboplatin, and paclitaxel. For the first 6 cycles (a cycle is a week) carboplatin and paclitaxel will be administered by IV every week. Pembrolizumab will be administered by IV on cycles 1 and 4. The next phase is the maintenance phase. This will occur from cycle 7-14 with each cycle being 6 weeks. Pembrolizumab will be administered every cycle.

Carboplatin is already approved in Canada for the following indications:

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Dustin Deming

Lead Sponsor

Trials

1

Recruited

20+

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

University of Wisconsin, Madison

Collaborator

Trials

1,249

Recruited

3,255,000+

Findings from Research

In a study of 98 advanced urothelial cancer patients, those who received radiotherapy to the primary tumor showed a significantly higher objective response rate to pembrolizumab (65% vs 19%) compared to those who did not receive radiotherapy.

Patients who had prior radiotherapy also experienced better overall survival rates (77% vs 50% at 12 months), suggesting that radiotherapy may enhance the effectiveness of pembrolizumab in treating advanced urothelial cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study. Fukushima, H., Kijima, T., Fukuda, S., et al.[2023]

In a phase Ib trial (KEYNOTE-028) involving 43 patients with advanced anal carcinoma, pembrolizumab showed a manageable safety profile, with 64% experiencing treatment-related adverse events, but no treatment-related deaths or discontinuations.

Among patients with PD-L1-positive tumors, pembrolizumab achieved a 17% overall response rate and a 58% disease control rate, indicating promising antitumor activity and supporting further research in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. Ott, PA., Piha-Paul, SA., Munster, P., et al.[2021]

In a phase II study involving 29 patients with locally advanced head and neck squamous cell carcinoma who were ineligible for cisplatin, the combination of pembrolizumab and radiotherapy showed promising efficacy, with a 24-month progression-free survival rate of 71%.

The treatment was generally well-tolerated, although a significant number of patients experienced grade 3/4 lymphopenia (58.6%), indicating the need for monitoring immune cell changes during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. Weiss, J., Sheth, S., Deal, AM., et al.[2023]

In a phase 2 study involving 112 patients with advanced anal squamous cell carcinoma, pembrolizumab demonstrated an objective response rate of 11%, with a higher response (15%) in patients with PD-L1-positive tumors, indicating its potential efficacy in this difficult-to-treat cancer.

The treatment was generally well-tolerated, with 61% of patients experiencing treatment-related adverse events, but no treatment-related deaths were reported, suggesting a favorable safety profile for pembrolizumab in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. Marabelle, A., Cassier, PA., Fakih, M., et al.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

Pembrolizumab, an anti-PD-1 antibody used for treating various cancers, can cause immune-related adverse events (IRAEs) affecting multiple body systems, including rare oral mucosal issues like glossitis.

In a case study of a 71-year-old male with lung cancer, treatment with oral prednisone effectively improved tongue ulcerations caused by pembrolizumab, highlighting the need for awareness of such rare side effects and their management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-Induced Immune-Mediated Glossitis. Alias, A., Hall, JA., Kulkarni, P., et al.[2022]

Pembrolizumab has been approved by the FDA as the first-line treatment for both HPV-positive and HPV-negative recurrent head and neck squamous cell carcinoma, marking it as a significant advancement in immunotherapy for this cancer type.

The approval allows pembrolizumab to be used either alone for tumors expressing PD-L1 or in combination with chemotherapy, highlighting the need for healthcare providers to be aware of and manage potential immune-related toxicities such as dermatitis and mucositis associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. Fazer, C., Price, KA.[2021]

A 74-year-old woman with lung adenocarcinoma developed fatal immune thrombocytopenia after receiving pembrolizumab following radiotherapy, highlighting a potential risk of severe immune-related adverse events (irAEs) when combining these treatments.

Flow cytometry analysis showed increased PD-1 and Ki-67 expression in T cells post-radiotherapy, suggesting that radiotherapy may enhance immune activation and contribute to the development of irAEs in patients undergoing anti-PD-1 therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. Tamanoi, D., Saruwatari, K., Imamura, K., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

In a phase 2 study involving 216 patients with stage III non-small cell lung cancer (NSCLC), the combination of pembrolizumab and concurrent chemoradiation therapy (cCRT) showed a high objective response rate of approximately 70.5% in cohort A and 70.6% in cohort B, indicating strong antitumor activity.

The treatment was associated with manageable safety, with grade 3 or higher pneumonitis occurring in 8.0% of cohort A and 6.9% of cohort B, suggesting that while there are risks, the benefits of this treatment approach may outweigh them for patients with locally advanced NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. Jabbour, SK., Lee, KH., Frost, N., et al.[2022]

In a trial involving 25 patients with locally advanced non-small-cell lung cancer (LA-NSCLC) and a PD-L1 tumor proportion score of ≥50%, the combination of pembrolizumab and risk-adapted radiotherapy achieved a 1-year progression-free survival rate of 76%, indicating strong efficacy without the use of chemotherapy.

The treatment was well-tolerated, with only 8% of patients experiencing grade 3 adverse events like colitis and esophagitis, and no higher-grade treatment-related adverse events reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selective Personalized Radioimmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial. Ohri, N., Jolly, S., Cooper, BT., et al.[2023]

References

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

Impact of radiotherapy to the primary tumor on the efficacy of pembrolizumab for patients with advanced urothelial cancer: A preliminary study. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal. [2021]

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

Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Pembrolizumab with Chemoradiation as Treatment for Muscle-invasive Bladder Cancer: Analysis of Safety and Efficacy of the PCR-MIB Phase 2 Clinical Trial (ANZUP 1502). [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Pembrolizumab-Induced Immune-Mediated Glossitis. [2022]

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

Management of Immune-Related Dermatitis and Mucositis Associated With Pembrolizumab in Metastatic Human Papillomavirus-Associated Squamous Cell Carcinoma of the Oropharynx. [2021]

9. Japan pubmed.ncbi.nlm.nih.gov

Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy. [2022]

10. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

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

Pembrolizumab Plus Concurrent Chemoradiation Therapy in Patients With Unresectable, Locally Advanced, Stage III Non-Small Cell Lung Cancer: The Phase 2 KEYNOTE-799 Nonrandomized Trial. [2022]

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

Selective Personalized Radioimmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial. [2023]