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Trial registered on ANZCTR


Registration number
ACTRN12618001573246
Ethics application status
Approved
Date submitted
30/05/2018
Date registered
20/09/2018
Date last updated
20/09/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Chemoradiation and immunotherapy for unresectable skin squamous cell carcinoma
Scientific title
A prospective study investigating the efficacy and toxicity of definitive chemoradiation and immunotherapy (CRIO) in locally and/or regionally advanced cutaneous squamous cell carcinoma
Secondary ID [1] 294389 0
Nil known
Universal Trial Number (UTN)
U1111-1214-8585
Trial acronym
CRIO
Linked study record
Nil known

Health condition
Health condition(s) or problem(s) studied:
skin cancer 307117 0
squamous cell carcinoma 307118 0
Condition category
Condition code
Cancer 306235 306235 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.

Intervention code [1] 301378 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 306082 0
The primary endpoints will be the safety of CRIO as determined by the incidence of grade 3 and 4 toxicities using CTCAE v4.03
Timepoint [1] 306082 0
Safety of treatment can be assessed while on treatment (maximum of 12 months post study entry).
Primary outcome [2] 306336 0
The rate of complete response.
Timepoint [2] 306336 0
Positron Emission Tomography (PET) at 12 weeks after chemoradiation is completed. Complete response defined as no residual disease at 12 weeks post treatment.
Secondary outcome [1] 347517 0
To assess overall survival using Kaplan Meier curve
Timepoint [1] 347517 0
60 months post treatment for survival outcomes
Secondary outcome [2] 348224 0
To assess locoregional control via clinical examination, CT/MRI and/or FDG-PET scans
Timepoint [2] 348224 0
60 months post-treatment for locoregional control outcomes

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Not applicable
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A two-stage minimax design will be applied, which requires an initial sample of 15 patients, with possibly an additional 13 patients required (total 28) subject to feasibility. The hypothesis that the proportion responding is 70% or more compared to the alternative hypothesis that 50% or fewer respond will be tested using a two-sided binomial test with a target significance level of 0.10 and power of 0.80. Fifteen patients would be recruited in the first stage and if 7 or fewer patients respond the trial will be terminated and we will conclude that the treatment is not more effective than standard treatment. If 8 or more patients respond, the trial may go to the second stage, recruiting a further 13 patients. Of the total of 28 patients, 18 or more must respond for the treatment to be considered better than current treatment. Sample size was calculated using the PASS 13 Power Analysis and Sample Size Software (NCSS, 2014)
For the first stage, the analysis will focus on descriptive statistics. Categorical variables will be summarised using frequencies and percentages and continuous variables will be summarised using means with standard deviations or as medians with interquartile ranges. Median survival time (with 95% CI) will be described and survival time will presented using a Kaplan-Meier curve. Safety/toxicity data will be presented according to the frequency of occurrence. The proportion of patients experiencing the primary outcome (complete response) will be presented with 95% confidence intervals and compared to the hypothesized null effect of 0.5 using an exact binomial test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2018
Actual
Date of last participant enrolment
Anticipated
1/11/2021
Actual
Date of last data collection
Anticipated
1/11/2023
Actual
Sample size
Target
15
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 11041 0
Royal Brisbane & Womens Hospital - Herston
Recruitment postcode(s) [1] 22837 0
4029 - Herston

Funding & Sponsors
Funding source category [1] 299026 0
Commercial sector/Industry
Name [1] 299026 0
Astra Zeneca
Country [1] 299026 0
Australia
Primary sponsor type
Hospital
Name
Metro North Hospital and Health Service
Address
Butterfield Street,
Herston, QLD 4029

Country
Australia
Secondary sponsor category [1] 298949 0
None
Name [1] 298949 0
Address [1] 298949 0
Country [1] 298949 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299961 0
Royal Brisbane and Women's Hospital Human Research Committee
Ethics committee address [1] 299961 0
Ethics committee country [1] 299961 0
Australia
Date submitted for ethics approval [1] 299961 0
21/03/2018
Approval date [1] 299961 0
14/09/2018
Ethics approval number [1] 299961 0
ERM ID: 40169

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 82094 0
Dr Charles Lin
Address 82094 0
Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street,
Herston, QLD 4029
Country 82094 0
Australia
Phone 82094 0
+61 7 3646 7687
Fax 82094 0
+61 7 3252 2746
Email 82094 0
Charles.Lin@health.qld.gov.au
Contact person for public queries
Name 82095 0
Charles Lin
Address 82095 0
Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street,
Herston, QLD 4029
Country 82095 0
Australia
Phone 82095 0
+61 7 3646 7687
Fax 82095 0
+61 7 3252 2746
Email 82095 0
Charles.Lin@health.qld.gov.au
Contact person for scientific queries
Name 82096 0
Charles Lin
Address 82096 0
Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street,
Herston, QLD 4029
Country 82096 0
Australia
Phone 82096 0
+61 7 3646 7687
Fax 82096 0
+61 7 3252 2746
Email 82096 0
Charles.Lin@health.qld.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma.2021https://dx.doi.org/10.1186/s13014-021-01795-5
N.B. These documents automatically identified may not have been verified by the study sponsor.