Chemoradiotherapy vs Immunotherapy with Radiation for Oral Cancer

Not currently recruiting at 28 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Canadian Cancer Trials Group

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Other malignancies, Autoimmune disorders, 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: 41

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines treatments for oral cancer to determine if immunotherapy with radiation is more effective than the standard chemoradiotherapy. The usual treatment combines chemotherapy with cisplatin and radiation. This trial tests whether adding immunotherapy drugs like durvalumab could help prevent cancer recurrence. It targets individuals with HPV-related oral cancer who have an intermediate risk and whose cancer has not spread beyond the local area. Participants must have a history of smoking and be able to manage daily activities well. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to advancing cancer treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that you should not be on any other anti-cancer therapy or participate in other clinical studies during the trial. It's best to discuss your current medications with the trial team to ensure they don't interfere with the study treatments.

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

In a previous study, patients taking durvalumab alone or with tremelimumab experienced manageable side effects. For example, a trial with 267 participants found these treatments were generally well-tolerated. Another study noted that a small number of patients using durvalumab and tremelimumab together experienced immune-related lung issues, such as pneumonitis.

Cisplatin, the chemotherapy drug used with radiation, serves as a standard treatment for various cancers. It can cause side effects like nausea and kidney problems, but doctors usually manage these effectively. Its common use indicates it is considered safe enough for treatment.

Overall, these studies suggest both new and existing treatments are generally well-tolerated, though side effects can occur. Participants should discuss potential risks with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for oral cancer because they offer innovative approaches compared to the standard chemoradiotherapy. Most treatments for this condition typically involve cisplatin with radiation, which can be taxing on the body. However, the study's treatment options include the use of durvalumab, an immunotherapy drug that helps the immune system target cancer cells more effectively, both with and without the addition of another immunotherapy agent, tremelimumab. These treatments leverage the body's immune response, potentially reducing some of the severe side effects associated with traditional chemotherapy, and opening new avenues for more personalized cancer care.

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

This trial will compare chemoradiotherapy with immunotherapy combined with radiation for oral cancer. Research has shown that durvalumab, one of the treatments in this trial, shows promise in treating head and neck cancers when used with radiation. Studies have found that adding tremelimumab to durvalumab, another treatment arm in this trial, can enhance its effectiveness by potentially boosting the immune system's ability to fight cancer. Although some studies did not fully achieve their main goals, patients still experienced noticeable benefits. Durvalumab, alone or with tremelimumab, has been effective for patients with certain cancers, such as those linked to human papillomavirus (HPV). Overall, these treatments offer new hope for reducing cancer recurrence in patients with oral cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Anna Spreafico

Principal Investigator

UNH/Princess Margaret Cancer Centre, Toronto ON Canada

Khalil Sultanem

Principal Investigator

The Jewish General Hospital, Montreal QC, Canada

Are You a Good Fit for This Trial?

This trial is for adults with intermediate-risk HPV-positive oropharyngeal squamous cell carcinoma that hasn't spread. They must be in good physical condition, not have had certain previous cancer treatments, and agree to use effective contraception. People with a history of severe allergies to study drugs, other cancers (except some exceptions), autoimmune diseases, uncontrolled illnesses, or who are pregnant can't join.

Inclusion Criteria

I can care for myself and weigh more than 30 kg.

I can start treatment within a week of being chosen for the trial.

I am using a highly effective method of birth control.

Exclusion Criteria

My heart's electrical activity (QTcF) is normal and I don't have a family history of long QT syndrome.

I have never had a severe immune reaction from treatments or been on strong immune-suppressing drugs recently.

I haven't taken strong immune-weakening meds in the last 28 days, except for small doses of steroids or specific treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Concurrent Treatment

Participants receive either Cisplatin or Durvalumab concurrently with radiation therapy

7 weeks

35 visits (in-person, daily radiation sessions)

Adjuvant Treatment

Participants receive adjuvant Durvalumab or Durvalumab with Tremelimumab

24 weeks

6 visits (in-person, every 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Durvalumab
• Radiation
• Tremelimumab

Trial Overview The study compares the effectiveness of cisplatin plus radiotherapy against durvalumab (an immunotherapy drug) plus radiotherapy followed by either more durvalumab or a combination of tremelimumab (another immunotherapy drug) and durvalumab in preventing cancer recurrence.

How Is the Trial Designed?

Group I: Radiation/Durvalumab + Adjuvant Durvalumab/Tremelimumab Experimental Treatment 3 Interventions

ARM CLOSED TO ACCRUAL WITH AMENDMENT #1

Group II: Radiation/Durvalumab + Adjuvant Durvalumab Experimental Treatment 2 Interventions

All patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Concurrent Phase: Durvalumab IV 1500 mg, days -7 and 22 (the second dose is given concurrently with RT). Adjuvant Phase (to start 4 weeks after completion of concurrent phase): Durvalumab IV 1500 mg q4 weekly for 6 doses.

Group III: Radiation/Cisplatin Active Control 2 Interventions

All patients will receive standard fractionation radiation therapy (RT) scheme: 70 Gy in 35 fractions over 7 weeks (i.e. 2 Gy per fraction) Cisplatin IV 100 mg/m2 days 1, 22, 43 concurrently with RT

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?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Published Research Related to This Trial

In a safety run-in phase of the DURIGAST PRODIGE 59 study involving 11 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, 63.6% experienced significant adverse events, primarily neutropenia, indicating a notable safety concern with the treatment combination.

The combination of FOLFIRI with Durvalumab and/or Tremelimumab showed an expected safety profile, allowing progression to the randomized phase II study, although careful monitoring for serious adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of FOLFIRI + Durvalumab +/- Tremelimumab in Second Line of Patients with Advanced Gastric Cancer: A Safety Run-In from the Randomized Phase II Study DURIGAST PRODIGE 59. Evrard, C., Aparicio, T., Soularue, E., et al.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a phase 3 study of 713 patients with stage III non-small-cell lung cancer, durvalumab significantly improved progression-free survival compared to placebo, with a median of 16.8 months versus 5.6 months, respectively.

Durvalumab also showed a higher response rate (28.4% vs. 16.0%) and longer median time to death or distant metastasis (23.2 months vs. 14.6 months), while safety profiles were similar between durvalumab and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. Antonia, SJ., Villegas, A., Daniel, D., et al.[2022]

In a trial involving 20 patients with recurrent/metastatic oral squamous cell carcinoma, the combination of camrelizumab with docetaxel and cisplatin showed a median overall survival of 14.4 months and an overall response rate of 40%, indicating promising efficacy.

The treatment was generally well tolerated, with 45% of patients experiencing grade ≥ 3 treatment-related adverse events, the most common being anemia and stomatitis, but no treatment-related deaths occurred.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of camrelizumab with docetaxel and cisplatin for the first line treatment in recurrent/metastatic oral squamous cell carcinoma. Ju, H., Wei, D., Wu, Y., et al.[2023]

In a phase 2 trial involving 90 patients with non-small-cell lung cancer resistant to PD-1/PD-L1 therapy, the combination of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) with radiotherapy did not show improved overall response rates compared to the therapy alone, leading to the trial's early termination due to futility.

The most common serious adverse events were manageable, but one patient in the low-dose radiotherapy group died from respiratory failure potentially related to the treatment, highlighting the need for careful monitoring in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial. Schoenfeld, JD., Giobbie-Hurder, A., Ranasinghe, S., et al.[2023]

In a study of 107 patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) and intensity-modulated radiotherapy (IMRT), the median progression-free survival (PFS) was 20.7 months, indicating effective treatment outcomes.

Factors associated with longer PFS included a favorable response to CCRT, a radiation dose of 62 Gy or more, and having stage IIIA NSCLC, while shorter durations of durvalumab treatment and lower radiation doses were linked to increased mortality risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy profiles of concurrent chemoradiotherapy with intensity-modulated radiotherapy followed by durvalumab in patients with unresectable stage III non-small cell lung cancer: A multicenter retrospective cohort study. Takeda, Y., Kusaba, Y., Tsukita, Y., et al.[2022]

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 study involving 10 patients receiving palliative radiotherapy (RT) combined with durvalumab, the treatment was well tolerated, with only 50% experiencing mild to moderate adverse events, primarily G2 mucositis, and no severe adverse events reported.

The treatment showed promising efficacy, with a 60% objective response rate in evaluable lesions and a significant decrease in tumor growth rate after RT, indicating that durvalumab combined with RT may effectively reduce tumor size in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Levy, A., Massard, C., Soria, JC., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03381183

IRX-2 Regimen and Durvalumab, for Incurable H&N ... The purpose of this study is to see if the IRX-2 regimen and Durvalumab, will have a tolerable safety profile and will increase the intratumoral immune profile ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9890138/

Safety and Efficacy of MEDI0457 plus Durvalumab in Patients ... While the primary efficacy endpoint was not reached, clinical benefit was encouraging. Translational Relevance. In patients with human papillomavirus (HPV)– ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.6065

Safety of radiotherapy with concurrent and adjuvant ... Background: MEDI4736 (durvalumab), a PD-L1 inhibitor, has shown promising antitumor activity and safety in head and neck squamous cell ...

4. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02827838/

Clinical Trial: NCT02827838 This pilot clinical trial studies how well durvalumab before surgery works in treating patients with oral cavity or oropharynx cancer.

5. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D419LC00001

Phase III open label study of MEDI 4736 with/without ... This is a randomized, open-label, multi-center, 3-arm, global Phase III study to determine the efficacy and safety of MEDI4736 + tremelimumab combination or ...

6. imfinzihcp.com imfinzihcp.com/hcc/unresectable/safety.html

Safety Profile of IMFINZI® (durvalumab) & IMJUDO® ... Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6439564/

The Phase 2 CONDOR Randomized Clinical Trial - PMC In this phase 2 randomized clinical trial of 267 patients, durvalumab monotherapy and durvalumab + tremelimumab demonstrated manageable toxic effects and ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03784066

Study Details | NCT03784066 | Durvalumab With or ... Newly diagnosed patients with SCCHN of the oral cavity, will be treated with a single dose of Durvalumab with or without Tremelimumab two weeks before scheduled ...

9. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2023/761270Orig1s000MultidisciplineR.pdf

761270Orig1s000 - accessdata.fda.gov The Applicant's E-R for safety analyses for durvalumab and tremelimumab were conducted with data from 327 patients for durvalumab and 326 ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT02262741

NCT02262741 | A Phase I Study to Evaluate the Safety, ... A Phase I Study to Evaluate the Safety, Tolerability and Efficacy of MEDI4736 (Durvalumab) With Tremelimumab in Head and Neck Cancer.