Quad Shot Radiotherapy in Combination With Immune Checkpoint Inhibition

NCT04454489 | Completed Phase 2 Results FDA Drug

• 3 other identifiers: IRB00066650WFBCCC 60320P30CA012197
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, non-randomized pilot study to evaluate the efficacy and tolerability of combination quad-shot palliative radiotherapy with immunotherapy for advanced/recurrent/metastatic head and neck cancer.

Conditions

Advanced Head and Neck Squamous Cell Carcinoma; Recurrent Head and Neck Squamous Cell Carcinoma; Metastatic Head-and-neck Squamous-cell Carcinoma; Stage III Cutaneous Squamous Cell Carcinoma of the Head and Neck; Locally Advanced Head and Neck Squamous Cell Carcinoma; Stage IV Cutaneous Squamous Cell Carcinoma of the Head and Neck

Outcome Measures

Primary Outcomes (1)

• Overall Response -

  Overall response will be measured according to RECIST 1.1 criteria to determine the percentage of participants with either a partial or complete response and the corresponding 95% Clopper-Pearson exact confidence interval. The best overall response is the best response recorded from the start of the treatment across all time points. COMPLETE RESPONSE: Disappearance (or decrease to the point at which measurement is not possible) of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (the sum may not be "0" if there are target nodes) PARTIAL RESPONSE: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters

  Up to 2 years

Secondary Outcomes (9)

• Response Rate in the Target Lesions

  Up to 2 years

• Response Rate in the Non-Target Lesions

  Up to 2 years

• Duration of Response at the Target Lesions - Mean Measurement

  Up to 2 years

• Duration of Response at the Target Lesions - Median Measurement

  Up to 2 years

• Progression-Free Survival

  Up to 2 years.

Study Arms (1)

Quad-shot palliative radiotherapy and Immunotherapy

EXPERIMENTAL

Systemic therapy (ICI) and radiotherapy will be administered according to the standard of care, according to the treating medical oncologist and radiation oncologist, respectively

Drug: Pembrolizumab (immunotherapy); Radiation: Quad-shot palliative radiotherapy

Interventions

Pembrolizumab (immunotherapy) DRUG

Pembrolizumab 200 mg will be given every 3 weeks to tumor progression or treatment tolerance.

Quad-shot palliative radiotherapy and Immunotherapy

Quad-shot palliative radiotherapy RADIATION

* Each cycle of quad-shot radiotherapy will be comprised of 14.8 Gy in 4 fractions (3.7 Gy per fraction) delivered twice daily (at least 6 hours apart) over two consecutive days. * All patients will receive 1 cycle of quad-shot radiotherapy between ICI cycles 2-3. * Subsequent cycles may occur between immunotherapy cycles 6-7 and 11-12, if more than 1 cycle can be safely delivered and the patient has experienced less than a partial response at protocol-specified tumor assessments (after C5 and C10). The eligibility for subsequent cycles will be at the discretion of the treating radiation oncologist. Therefore, the total prescription dose will be: * 14.8 Gy in 4 fractions for those that complete 1 cycle (all patients will receive 1 cycle) * 19.6 Gy in 8 fractions for those that complete 2 cycles * 44.4 Gy in 12 fractions for those that complete 3 cycles

Quad-shot palliative radiotherapy and Immunotherapy

Eligibility Criteria

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

You may qualify if:

• Advanced, recurrent or metastatic head and neck squamous cell carcinoma, as defined by clinical or pathological diagnosis of any of the following:
• Locally advanced head and neck squamous cell carcinoma not suitable for curative local treatment.
• Locally recurrent head and neck squamous cell carcinoma not suitable for curative local treatment within or outside a previously irradiated tissue.
• Metastatic head and neck squamous cell carcinoma.
• Target site in the head and neck region amenable to quad-shot palliative radiotherapy, for which palliative radiotherapy is recommended, as determined by the treating radiation oncologist.
• Age 18 years or greater at time of registration.
• ECOG Performance Status of 0-2.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
• Willingness to provide blood and saliva samples for exploratory research purposes.
• Organ and Marrow Function as defined below: Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L, hemoglobin ≥ 9.0 g/dL, serum bilirubin ≤ 1.5 x ULN (institutional upper limit of normal), AST and ALT ≤ 2.5 x ULN (institutional upper limit of normal), serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• MALES: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) (divided by) 72 x serum creatinine (mg/dL).
• FEMALES: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 (divided by) 72 x serum creatinine (mg/dL)

You may not qualify if:

• Radiation therapy to the planned quad-shot radiotherapy target region within 30 days of registration.
• Prior radiotherapy to the head and neck that precludes safe delivery of study radiotherapy, as determined by the treating radiation oncologist.
• Active medical conditions that are contraindications to study radiotherapy (i.e. scleroderma), as determined by the treating radiation oncologist.
• Pregnant or lactating women are excluded from this study because radiotherapy is contraindicated in pregnancy and because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with immunotherapy.
• Participation in another clinical study with an investigational product during the last 3 months.
• Any previous treatment with a PD1 or PD-L1 inhibitor.
• Any anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) within the last 30 days. Note: this excludes palliative radiotherapy to the non-target site.
• Mean QT interval corrected for heart rate (QTc) ≥470 ms except for patients with pacemaker who have a paced ventricular rhythm.
• Current or prior use of immunosuppressive medication within 30 days, with exceptions of intranasal and inhaled corticosteroids, a brief, non-sustained corticosteroids treatment for incidental problems such as allergies (at the discretion of the treating physician) or sustained systemic corticosteroids treatment at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid except for short course of prednisone that is prescribed for acute allergic situations or for prevention of an allergy to contrast substance utilized for imaging studies.
• Any unresolved toxicity (\>CTCAE grade \> 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1.
• Active or prior documented autoimmune disease within the past 2 years, NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis).
• History of primary immunodeficiency.
• History of allogeneic organ transplant.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Wake Forest Baptist Comprehensive Cancer Center

Winston-Salem, North Carolina, 27157, United States

Location

Related Publications (1)

• Hughes RT, Gebeyehu RR, Kalada JM, Lycan TW, Frizzell BA, Kinney RD, D'Agostino RB, Bunch PM, Triozzi P, Zhang W, Furdui CM, Porosnicu M. Quad-shot-immunotherapy: quad-shot radiotherapy with pembrolizumab for advanced/recurrent head and neck cancer. Future Oncol. 2023 Jul;19(22):1523-1534. doi: 10.2217/fon-2022-1146. Epub 2023 May 18.

  PMID: 37199326 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; Immunotherapy

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)

Immunomodulation; Biological Therapy; Therapeutics

Results Point of Contact

• Title: Principal Investigator
• Organization: Wake Forest Baptist Comprehensive Cancer Center

mporosnicu@wakehealth.edu

336 -713-5440

Study Officials

• Mercedes Porosnicu, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2020
• First Posted: July 1, 2020
• Study Start: February 25, 2021
• Primary Completion: February 18, 2025
• Study Completion: April 30, 2025
• Last Updated: November 19, 2025
• Results First Posted: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)