Immunotherapy and SBRT for Metastatic Head and Neck Carcinomas

NCT03283605 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: ESR-16-12361
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 3

Brief Summary

Immunotherapy targeting the PD-1/PD-L1 pathway had previously been shown to be efficacious in the treatment of patients with metastatic head and neck squamous cell carcinomas. Stereotactic Body Radiotherapy (SBRT) to metastatic lesions causes localized cancer cell killing and the release of cancer cell debris, which could stimulate the immune system in the presence of immunotherapy. The purpose of this study is to assess the tolerability and efficacy of combining Durvalumab (MEDI4736), Tremelimumab and SBRT in controlling cancer progression. SBRT will be administered to patients while they are receiving Durvalumab and Tremelimumab.

Conditions

Head and Neck Squamous Cell Carcinoma; Metastatic Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (2)

• Acute toxicities of the treatment

  The rate of Grade 3-5 combination TTC-related toxicities within 12 weeks from the start of SBRT treatments. The results will be tabulated to examine their frequency, organ systems affected, severity, and relationship to study treatment. Terminology Criteria for Adverse Events (CTCAE) V4.03 will be used for grading of AEs. Investigators will provide their assessment of causality as 1) unrelated, 2) unlikely, 3) possibly related, 4) probably, or 5) definitely related.

  3 months

• Progression Free Survival (PFS)

  To evaluate whether the combination SBRT with Durvalumab and Tremelimumab will improve the progression-free survival of patients. Response will be assessed as per RECIST version 1.1.

  6 months

Secondary Outcomes (4)

• Local control (LC)

  2 years

• Progression-free survival (PFS)

  2 years

• Overall survival (OS)

  2 years

• Abscopal events

  2 years

Study Arms (1)

Durvalumab + tremelimumab and SBRT

EXPERIMENTAL

All subjects will receive durvalumab (1500 mg IV q4week) and tremelimumab (75mg q4week) for 4 doses, followed by durvalumab alone (1500 mg IV q4week) until disease progression, unacceptable toxicity or patient withdrawal. SBRT will be administered between cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.

Radiation: SBRT; Drug: Durvalumab; Drug: Tremelimumab

Interventions

SBRT RADIATION

SBRT to 2-5 oligometastases will be administered between Cycle 2 and 3 of durvalumab and tremelimumab. All SBRT will be completed within a 3-week period.

Durvalumab + tremelimumab and SBRT

Durvalumab DRUG

Durvalumab (1500 mg IV q4weeks) for 4 cycles in combination with tremelimumab. Then, durvalumab alone until confirmed disease progression, death, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria met.

Durvalumab + tremelimumab and SBRT

Tremelimumab DRUG

Tremelimumab (75mg IV q4weeks) for 4 cycles in combination with Durvalumab.

Durvalumab + tremelimumab and SBRT

Eligibility Criteria

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

You may qualify if:

• Pathologically (histologically or cytologically) confirmed diagnosis HNSCC at a metastatic site. This includes histologic variants of SCC such as spindle cell carcinoma, poorly differentiated keratin-positive carcinoma, and lymphoepithelioma. The pathology can come from the most accessible site and does not need to be from the time of diagnosis.
• ≥2 locoregional and/or extracranial metastatic lesions (no brain metastases) that are treatable by SBRT. Lesions that are not measurable per RECIST v1.1 must show progression on 2 consecutive imaging studies with a minimum increase of 1 mm, and must be a mimimum size of 5 mm at time of enrollment. .
• ≤ 4 prior treatment lines with systemic therapy
• ≥2 measurable disease (RECIST) consisting of extracranial metastatic lesions (no brain metastasis) that are treatable by SBRT.
• ≤ 10 metastatic lesions
• Life expectancy \> 24 weeks
• Evaluation by a radiation oncologist within 45 days prior to study registration
• Evaluation by a medical oncologist within 45 days prior to study registration
• Body weight \>30kg
• The following imaging workup to document metastases within 45 days prior to study registration:
• CT scans of the chest, abdomen and pelvis OR whole body PET/CT
• ≥ 18 years of age at time of study entry
• Up to 4 prior treatment lines with systemic therapy are allowed
• Eastern Cooperative Oncology Group/World Health Organisation (ECOG/WHO) performance status score of ≤ 1
• Patients with locoregional recurrence(s) can be included only if they have evidence of distant metastasis; patients with locoregional recurrences which are symptomatic and/or potentially affect quality of life may undergo palliative radiation therapy to this region prior to enrollment on the protocol at the discretion of the treating physician. However, a minimum of 6 weeks must elapse before receiving protocol treatment.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Nasopharyngeal carcinoma
• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• \>4 prior treatment lines with systemic therapy
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies) ≤ 30 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg. hormone replacement therapy) is acceptable.
• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of allogenic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead
• AstraZeneca: collaborator

Study Sites (3)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

London Regional Cancer Program of the Lawson Health Research Institute

London, Ontario, N6A 4L6, Canada

Location

Centre Hospitalier de l'Université de Montréal

Montreal, Quebec, H2L 4M1, Canada

Location

Related Publications (1)

• Bahig H, Aubin F, Stagg J, Gologan O, Ballivy O, Bissada E, Nguyen-Tan FP, Soulieres D, Guertin L, Filion E, Christopoulos A, Lambert L, Tehfe M, Ayad T, Charpentier D, Jamal R, Wong P. Phase I/II trial of Durvalumab plus Tremelimumab and stereotactic body radiotherapy for metastatic head and neck carcinoma. BMC Cancer. 2019 Jan 14;19(1):68. doi: 10.1186/s12885-019-5266-4.

  PMID: 30642290 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open-label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single group assignment

Study Record Dates

• First Submitted: September 12, 2017
• First Posted: September 14, 2017
• Study Start: July 17, 2018
• Primary Completion: July 31, 2024
• Study Completion: December 31, 2024
• Last Updated: June 28, 2024

Record last verified: 2024-06

Locations

CA (3)