NCT03522584

Durvalumab, Tremelimumab and Hypofractionated Radiation Therapy in Treating Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Terminated Phase 1, PHASE2 Results posted Last updated 12 June 2023

What this trial tests

Phase 1, PHASE2 trial testing Durvalumab in Metastatic Head and Neck Squamous Cell Carcinoma in 6 participants. Terminated before completion.

Timeline

17 May 2018

Primary endpoint
16 December 2021

19 January 2022

Quick facts

Lead sponsor	University of Washington
Phase	Phase 1, PHASE2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	6
Start date	17 May 2018
Primary completion	16 December 2021
Estimated completion	19 January 2022
Sites	1 location across United States

Drugs / interventions tested

• Durvalumab — full drug profile →
• Laboratory Biomarker Analysis — full drug profile →
• Stereotactic Body Radiation Therapy — full drug profile →
• Tremelimumab (TREMELIMUMAB) — full drug profile →
• Hypofractionated Image-Guided Radiation Therapy

Conditions studied

• Metastatic Head and Neck Squamous Cell Carcinoma — all drugs for Metastatic Head and Neck Squamous Cell Carcinoma →
• Recurrent Head and Neck Squamous Cell Carcinoma — all drugs for Recurrent Head and Neck Squamous Cell Carcinoma →

Sponsor

University of Washington

Who can join

18 and older, any sex, with Metastatic Head and Neck Squamous Cell Carcinoma or Recurrent Head and Neck Squamous Cell Carcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients With Adverse Effects Graded According to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0 Primary · From the start of study treatment up to 3 months after last study treatment, up to 38 months

Toxicities will be summarized as the number and percentage of patients with each type of toxicity, per Criteria for Adverse Events version 4.0

Anorexia

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Concentration Impairment

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Cough

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	2

Depression

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Diarrhea

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Dizziness

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Dry Mouth

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Fatigue

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	4

Response Rate Secondary · Up to 2 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Stable Disease

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	3

Progressive Disease

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Complete Response

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	1

Progression-free Survival Secondary · From the date of study enrollment for up to 2 years

Survival estimates will be calculated using the Kaplan-Meier method. Progression free survival is measured in months. PFS is defined as the amount of time between treatment initiation and when the disease progresses per RECIST 1.1 criteria

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	7	± 2

Overall Survival Secondary · From the date of study enrollment for up to 2 years

Survival estimates will be calculated using the Kaplan-Meier method. Overall survival is measured in months. OS is defined as the amount of time between treatment initiation and when the patient is deceased.

Group	Value	95% CI
Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)	8	4 – 14

Adverse events — posted to ClinicalTrials.gov

Time frame: 3 years, 2 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Treatment (Tremelimumab, Durvalumab, HIGRT, SBRT)

Serious: 0/6 (0%)

Deaths: 6/6

Other adverse events (29 terms — click to expand)

Reaction	System	Treatment (Tremelimumab, D…
Fatigue	General disorders	—
Weight Loss	Metabolism and nutrition disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Fever	Infections and infestations	—
Headache	General disorders	—
Anorexia	Metabolism and nutrition disorders	—
Concentration Impairment	Nervous system disorders	—
Depression	Nervous system disorders	—
Diarrhea	Gastrointestinal disorders	—
Dizziness	Nervous system disorders	—
Dry Mouth	Metabolism and nutrition disorders	—
Hypercalcemia	Endocrine disorders	—
Hyperalbuminemia	Endocrine disorders	—
Increased Dyspnea	Respiratory, thoracic and mediastinal disorders	—
Non-Cardiac Chest Pain	Musculoskeletal and connective tissue disorders	—
Infusion Related Reaction	Injury, poisoning and procedural complications	—
Mucositis	Gastrointestinal disorders	—
Nausea	Gastrointestinal disorders	—
Neck Pain	Musculoskeletal and connective tissue disorders	—
Night Sweats	Skin and subcutaneous tissue disorders	—
Otitis Externa	Musculoskeletal and connective tissue disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Right Shoulder Pain	Musculoskeletal and connective tissue disorders	—
Maculopapular Rash	Skin and subcutaneous tissue disorders	—
Rhinorrhea	Respiratory, thoracic and mediastinal disorders	—
Shingles	Infections and infestations	—
Sore Throat	Respiratory, thoracic and mediastinal disorders	—
Wheezing	Respiratory, thoracic and mediastinal disorders	—
Oral Thrush	Infections and infestations	—

Data from ClinicalTrials.gov NCT03522584 adverse events section.

Sponsor's own description

This phase I/II trial studies the side effects of durvalumab, tremelimumab and hypofractionated radiation therapy in treating patients with head and neck squamous cell carcinoma that has come back (recurrent) or that has spread to other places in the body (metastatic). Immunotherapy with monoclonal antibodies, such as durvalumab and tremelimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more tumor cells and have fewer side effects. Giving durvalumab, tremelimumab, and hypofractionated radiation therapy may work better in treating patients with recurrent or metastatic head and neck squamous cell carcinoma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer.
   Hutchinson MND, Mierzwa M, D'Silva NJ. · · 2020 · cited 126× · PMID 32157215 · DOI 10.1038/s41388-020-1250-3
2. Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy.
   Horton JD, Knochelmann HM, Day TA, Paulos CM, et al · · 2019 · cited 65× · PMID 30961829 · DOI 10.1016/j.trecan.2019.02.007
3. Combining Radiation and Immune Checkpoint Blockade in the Treatment of Head and Neck Squamous Cell Carcinoma.
   Manukian G, Bar-Ad V, Lu B, Argiris A, et al · · 2019 · cited 57× · PMID 30895168 · DOI 10.3389/fonc.2019.00122
4. Radiotherapy and Immunotherapy for Head and Neck Cancer: Current Evidence and Challenges.
   Qian JM, Schoenfeld JD. · · 2020 · cited 47× · PMID 33614492 · DOI 10.3389/fonc.2020.608772
5. Immune deserts in head and neck squamous cell carcinoma: A review of challenges and opportunities for modulating the tumor immune microenvironment.
   Farlow JL, Brenner JC, Lei YL, Chinn SB. · · 2021 · cited 34× · PMID 34218062 · DOI 10.1016/j.oraloncology.2021.105420
6. Immunotherapy Advances in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma and Its Relationship With Human Papillomavirus.
   Wang H, Zhao Q, Zhang Y, Zhang Q, et al · · 2021 · cited 33× · PMID 34305889 · DOI 10.3389/fimmu.2021.652054
7. Immune Checkpoints Pathways in Head and Neck Squamous Cell Carcinoma.
   Veigas F, Mahmoud YD, Merlo J, Rinflerch A, et al · · 2021 · cited 30× · PMID 33804419 · DOI 10.3390/cancers13051018
8. Current and Emerging Molecular Therapies for Head and Neck Squamous Cell Carcinoma.
   Kordbacheh F, Farah CS. · · 2021 · cited 25× · PMID 34771633 · DOI 10.3390/cancers13215471