Clinical trial NCT01104922: Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
Official title: Re-irradiation With Fractionated Stereotactic Radiosurgery Plus Cetuximab in Patients With Recurrent Squamous Cell Carcinoma of the Head and Neck
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Cell Carcinoma of the Head and Neck
Keywords: Fractionated Stereotactic Radiosurgery
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
First posted: 2010-04-16
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial examines survival and toxicity in previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN) treated with radiosurgery and cetuximab and to evaluate the acute and late toxicities associated with the above therapy.

Detailed description: Squamous cell carcinoma of the head and neck is the sixth most common malignancy worldwide with approximately 500,000 cases worldwide yearly. There were an estimated 39,250 new cases and 11,000 deaths in the United States in 2005 (Jemal 2005, Spitz MR). Despite major improvements in the treatment of SCCHN in recent years which include the introduction of concurrent chemoradiotherapy as an effective primary or postoperative therapy, the five-year survival rate for patients with SCCHN in the United States and other developed countries remains poor as nearly 50-60% of these patients will die as a direct result of recurrent locoregional disease. This study aims to determine the 1-year progression-free survival (PFS) of previously irradiated patients with squamous cell carcinoma of the head and neck (SCCHN) treated with radiosurgery and cetuximab and to evaluate the acute and late toxicities associated with the therapy.

Eligibility criteria: Inclusion Criteria:

* Histologically proven recurrent squamous cell carcinoma of the head and neck (SCCHN), who has received prior radiotherapy with or without chemotherapy. New primary is allowed if location is in a previously irradiated field. Biopsy is recommended for each recurrence; but is not mandated per study. This will be at the discretion of the principal investigator.
* Prior radiation dose of at least 60 Gy.
* Disease confined to locoregional site and can be encompassed in a stereotactic radiosurgery "portal"
* Tumor must be deemed to be inoperable or unresectable either by clinical or radiographic criteria. These criteria include encasement of great vessels, vertebral invasion or undue peri-operative risk.
* Prior surgery for recurrent or new SCCHN is allowed in previously irradiated patients. A minimum of 4 weeks should elapse between any surgery and treatment on study. However, high risk pathologic features should be present, such as positive margins, positive lymphadenopathy, perineural or angiolymphatic invasion. Measurable disease must be present for assessment of response.
* Karnofsky performance status \> 60 (ECOG 0-2)
* Prior treatment with an EGFR Inhibitor is allowed if it was a part of prior curative therapy and was completed at least 30 days prior to commencement of study therapy
* Any number of prior chemotherapy regimens are allowed
* Measurable disease on imaging studies (MRI, CT, PET-CT or physical exam)
* Age \> 18
* Estimated life expectancy \> 12 weeks
* No prior radiation therapy or chemotherapy within 1 month of study enrollment
* No prior chemotherapy or targeted therapy within the previous 4 weeks
* ANC \> 1000, PLT\>75,000, Serum creatinine\<2.5 mg/dL, Bilirubin \<1.5 x upper limits of normal (ULN)
* Diabetes must be controlled prior to PET-CT scanning (blood glucose \<200 mg/dL)
* Ability to provide written informed consent

Exclusion Criteria:

* Evidence of distant metastasis on upright chest x-ray (CXR), computed tomography (CT) or other staging studies
* History of any cancer other than SCCHN (except non-melanoma skin cancer or carcinoma in situ of the cervix) within the last 5 years.
* Patients in their reproductive age group should use an effective method of birth control. Patients who are breast-feeding, or have a positive pregnancy test will be excluded from the study
* Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator
* Concurrent serious infection
* History of known hypersensitivity to cetuximab or similar agents

Primary outcomes:
measure: 1-year Local Progression-free Survival (PFS)
timeFrame: At 1-year
measure: 1-year Locoregional Progression-free Survival (PFS)
timeFrame: At 1-year
measure: 1-year Distant Progression-free Survival (PFS)
timeFrame: At 1-year
Secondary outcomes:
measure: 1-year Progression-free Survival (PFS)
timeFrame: At 1-year
measure: Overall Survival (OS)
timeFrame: Up to 2 years
measure: Overall Response (OR)
timeFrame: Up to 2 years
measure: Changes in Tumor Glucose Metabolism
timeFrame: Up to 24 months / post therapy
measure: Changes in Tumor Hypoxia.
timeFrame: Up to 24 months; before and after treatment
measure: Quality of Life (QoL)
timeFrame: Baseline, 6-8 weeks post-treatment; up to 16 months
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: David A Clump, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vargo JA, Ferris RL, Ohr J, Clump DA, Davis KS, Duvvuri U, Kim S, Johnson JT, Bauman JE, Gibson MK, Branstetter BF, Heron DE. A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 2015 Mar 1;91(3):480-8. doi: 10.1016/j.ijrobp.2014.11.023. Epub 2015 Jan 30.