None listed
Conditions
Brief summary
This study is examining the efficacy and safety of a ChemoRadiation and ImmunOtherapy protocol called CIRO in unresectable skin squamous cell carcinoma. Who is it for? You may be eligible for this study if you are aged 18 or older and have an advance biopsy proven skin squamous cell carcinoma which can not be removed by surgery Study details All participants will receive the standard treatment (chemoradiation) for 7 weeks in conjunction with an immunotherapy medication called Durvalumab. CRIO stands for ChemoRadiation and ImmunOtherapy which involves the combination of radiotherapy, chemotherapy, and immunotherapy. Patients with advance skin squamous cell carcinoma which can not be removed by surgery represent a clinical challenge. These patients are often treated by radiotherapy and chemotherapy. Such approach is 50% successful in making the skin cancer disappear completely. We are hoping to improve the 50% figure to 70% by adding an immunotherapy called durvalumab.
Interventions
This is a single arm phase 2 efficacy study. Fifteen patients with locally and/or regionally advanced cutaneous Squamous Cell Carcinoma (SCC) deemed suitable for definitive immunochemoradiation
All patients will receive radiotherapy (70Gy in 35 fractions over 7 weeks), Carboplatin (Area under curve 2.0), and durvalumab during the first 7 weeks of treatment, Radiotherapy will be given daily, Monday to Friday, for 7 weeks. Carboplatin will be given intravenously at weekly intervals for 7 weeks w
This is a single arm phase 2 efficacy study. Fifteen patients with locally and/or regionally advanced cutaneous Squamous Cell Carcinoma (SCC) deemed suitable for definitive immunochemoradiation All patients will receive radiotherapy (70Gy in 35 fractions over 7 weeks), Carboplatin (Area under curve 2.0), and durvalumab during the first 7 weeks of treatment, Radiotherapy will be given daily, Monday to Friday, for 7 weeks. Carboplatin will be given intravenously at weekly intervals for 7 weeks while patients are having radiotherapy. Durvalumab (1500mg per dose) will be given intravenously at week 1 and week 5 during the 7 weeks of radiotherapy. Once radiation and Carboplatin is completed, durvalumab will continue to be administerd at weeks 9, 13, and 17. Patients will then be assessed by a nuclear medicine scan at week 19 to determine if further durvalumab is required.
Sponsors
Metro North Hospital and Health Service
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
• Written informed consent • greater and equal to 18 years old; • Body weight >30kg • Pathologically confirmed skin SCC; • Patients’ disease deemed unresectable or not suitable for surgery by the head and neck multidisplinary team; • Adequate performance status (ECOG 0-1); • Must have a life expectancy of at least 12 weeks • Assessable disease • Adequate normal organ and marrow function • Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause • Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion criteria
Any disease, condition, physical examination finding or clinical laboratory finding which, in the opinion of the investigator, makes the patient unsuitable for curative intent CRIO: • Immunosuppression secondary to blood disorders (e.g. chronic lymphocytic leukaemia) or immunosuppressant for organ transplants or human immunodeficiency virus (HIV) Active infection with Hepatitis B or Hepatitis C virus • Active uncontrolled bleeding: • Previous chemotherapy and/or radiotherapy to the head and neck region which would preclude re-treatment; • Contra-indication for radiotherapy or chemotherapy; • Claustrophobia; • Unable to maintain follow up for a minimum of 1 year. • Participation in another clinical study with an investigational product during the last 6 months • 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 • Any previous treatment with a PD1 or PD-L1 inhibitor, including Durvalumab (MEDI4736) (Unless prior PD1/PD-L1 inhibition is a specific entry criterion) • Receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolization, monoclonal antibodies, other investigational agent) 60 days prior to the first dose of study drug (60 days prior to the first dose of study drug for patients who have received prior TKIs [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.) • Current or prior use of immunosuppressive medication within 14 days before the first dose of Durvalumab (MEDI4736), with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. • Any unresolved toxicity NCI CTCAE v 4.03 Grade greater or equal to 2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria • Any concurrent investigational product, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. • History of allogenic organ transplantation. • Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., 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 hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement - Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice). • Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine whilst receiving IP and up to 30 days after the last dose of IP. • Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of Durvalumab (MEDI4736) monotherapy. • Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
Outcome results
None listed