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

NCT03522584 | Terminated Phase 1 Results DMC FDA Drug FDA Device

• 4 other identifiers: 9881NCI-2018-00540P30CA015704RG1717067
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Adverse Effects Graded According to Common Terminology Criteria for Adverse Events (CTCAE) v. 4.0

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

  From the start of study treatment up to 3 months after last study treatment, up to 38 months

Secondary Outcomes (3)

• Response Rate

  Up to 2 years

• Progression-free Survival

  From the date of study enrollment for up to 2 years

• Overall Survival

  From the date of study enrollment for up to 2 years

Study Arms (1)

Treatment (tremelimumab, durvalumab, HIGRT, SBRT)

EXPERIMENTAL

Patients receive tremelimumab IV over 1 hour and durvalumab IV over 1 hour on day 1, week 1. Treatment repeats every 4 weeks for up to 4 cycles or every 6 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive durvalumab IV over 60 minutes on day 1, week 16. Treatment repeats every 4 weeks for up to 9 cycles or every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo hypofractionated radiation therapy using either HIGRT or SBRT over 3 fractions QOD during week 3.

Biological: Durvalumab; Other: Laboratory Biomarker Analysis; Radiation: Stereotactic Body Radiation Therapy; Biological: Tremelimumab; Procedure: Hypofractionated Image-Guided Radiation Therapy

Interventions

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI-4736, MEDI4736

Treatment (tremelimumab, durvalumab, HIGRT, SBRT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (tremelimumab, durvalumab, HIGRT, SBRT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (tremelimumab, durvalumab, HIGRT, SBRT)

Tremelimumab BIOLOGICAL

Given IV

Also known as: Anti-CTLA4 Human Monoclonal Antibody CP-675,206, CP-675, CP-675,206, CP-675206, Ticilimumab

Treatment (tremelimumab, durvalumab, HIGRT, SBRT)

Hypofractionated Image-Guided Radiation Therapy PROCEDURE

Undergo HIGRT

Also known as: Hypofractionated Image-Guided Radiotherapy

Treatment (tremelimumab, durvalumab, HIGRT, SBRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven recurrent/metastatic squamous cell carcinoma arising from a previous head and neck primary site, and located within the head and neck region, lung mediastinum, lymph nodes, soft tissue metastases or bone, and who are not candidates for curative intent therapy
• An actual body weight \> 40kg
• Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy
• Have received any number lines of prior systemic therapy (including systemic therapy in the curative intent setting, and including a platinum containing regimen)
• Have received an anti-PD1 or anti PDL1 monoclonal antibody
• Have a target lesion/s deemed suitable by the treating physicians for hypofractionated radiation therapy (HIGRT or SBRT) with the intent of palliation or prevention of symptoms; this lesion must be: a) 1-3 non overlapping sites in the head and neck region OR b) metastatic lesions outside the head and neck (H\&N) region in the lung mediastinum, soft tissue metastases, lymph nodes or bone (a minimum of 1 and a maximum 5 lesions will be irradiated), provided there is no significant overlap between the lesions; patients should have RECIST 1.1 criteria measurable disease in addition to the lesion/s treated with radiation; if the site/s of radiation were previously radiated to high dose RT (\> 50 Gy), there should be \> 6 month time interval between the last dose of radiation and the start of radiation
• Have the ability to tolerate required radiotherapy-related procedures (e.g.: lie flat and hold position for treatment) as determined by the treating physician
• Be willing and able to provide written informed consent for the trial and comply with the study visit requirements
• Have measurable disease based on RECIST 1.1. (in addition to the lesion/s that will be treated with hypofractionated radiation therapy)
• Have provided tissue from an archival tissue sample or newly obtained core or excisional biopsy of a tumor lesion
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Hemoglobin \>= 9.0 g/dL (should be performed within 10 days of treatment initiation)
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L (\>= 1500 per mm\^3) (should be performed within 10 days of treatment initiation)
• Platelet count \>= 100 x 10\^9/L (\>= 100,000 per mm\^3) (should be performed within 10 days of treatment initiation)
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN) (should be performed within 10 days of treatment initiation); this will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician

You may not qualify if:

• Has a body weight =\< 40kg at the time of enrollment
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
• Has a target lesion/s for radiotherapy that is \> 5 cm (\> 50 cc) in greatest dimension
• Has a target lesion/s in a region that previously received high dose radiation therapy (RT) (\> 50 Gy) demonstrating any of the following:
• carotid artery encasement (\> 180 degrees)
• unprotected carotid artery (i.e. skin is directly over the carotid without intervening soft tissue, especially after prior neck dissection without a vascularized free flap) (a\&b due to risk of carotid blow out)
• skin infiltration by tumor (due to risk of fistula)
• located in the larynx/hypopharynx primaries (due airway threat)
• treated with high dose radiation therapy (\> 50 Gy) within 6 months or less of trial enrollment
• Any prior grade \>= 3 immune-related adverse event (irAE) while receiving a prior immunotherapy agent, or any unresolved irAE \> grade 1
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or tremelimumab; the following are exceptions to this criterion:
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., computed tomography \[CT\] scan premedication)
• Has received a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =\< grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator
• AstraZeneca: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

durvalumab; Immunoglobulin G; Disulfides; Radiosurgery; tremelimumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Cristina Rodriguez
• Organization: University of Washington

rodrigcr@uw.edu

2066066748

Study Officials

• Cristina P. Rodriguez

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 30, 2018
• First Posted: May 11, 2018
• Study Start: May 17, 2018
• Primary Completion: December 16, 2021
• Study Completion: January 19, 2022
• Last Updated: June 12, 2023
• Results First Posted: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)