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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
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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
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Secondary ID [1]
294389
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Nil known
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Universal Trial Number (UTN)
U1111-1214-8585
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Trial acronym
CRIO
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Linked study record
Nil known
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Health condition
Health condition(s) or problem(s) studied:
skin cancer
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squamous cell carcinoma
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Condition category
Condition code
Cancer
306235
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0
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Non melanoma skin cancer
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Intervention/exposure
Study type
Interventional
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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.
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Intervention code [1]
301378
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Treatment: Drugs
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Comparator / control treatment
No control group
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Control group
Uncontrolled
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Outcomes
Primary outcome [1]
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The primary endpoints will be the safety of CRIO as determined by the incidence of grade 3 and 4 toxicities using CTCAE v4.03
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Assessment method [1]
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Timepoint [1]
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Safety of treatment can be assessed while on treatment (maximum of 12 months post study entry).
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Primary outcome [2]
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The rate of complete response.
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Assessment method [2]
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Timepoint [2]
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Positron Emission Tomography (PET) at 12 weeks after chemoradiation is completed. Complete response defined as no residual disease at 12 weeks post treatment.
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Secondary outcome [1]
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To assess overall survival using Kaplan Meier curve
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Assessment method [1]
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Timepoint [1]
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60 months post treatment for survival outcomes
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Secondary outcome [2]
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To assess locoregional control via clinical examination, CT/MRI and/or FDG-PET scans
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Assessment method [2]
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Timepoint [2]
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60 months post-treatment for locoregional control outcomes
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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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Single group
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Other design features
Not applicable
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Phase
Phase 2
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Type of endpoint/s
Safety/efficacy
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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.
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Recruitment
Recruitment status
Not yet recruiting
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Date of first participant enrolment
Anticipated
1/11/2018
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Actual
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Date of last participant enrolment
Anticipated
1/11/2021
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Actual
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Date of last data collection
Anticipated
1/11/2023
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Actual
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Sample size
Target
15
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
QLD
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Recruitment hospital [1]
11041
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Royal Brisbane & Womens Hospital - Herston
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Recruitment postcode(s) [1]
22837
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4029 - Herston
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Funding & Sponsors
Funding source category [1]
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Commercial sector/Industry
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Name [1]
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Astra Zeneca
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Address [1]
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AstraZeneca Pty Ltd,
66 Talavera Road, Macquarie Park, NSW, 2113
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Country [1]
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Australia
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Primary sponsor type
Hospital
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Name
Metro North Hospital and Health Service
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Address
Butterfield Street,
Herston, QLD 4029
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Country
Australia
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Secondary sponsor category [1]
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None
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Name [1]
298949
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Address [1]
298949
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Country [1]
298949
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Ethics approval
Ethics application status
Approved
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Ethics committee name [1]
299961
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Royal Brisbane and Women's Hospital Human Research Committee
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Ethics committee address [1]
299961
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Butterfield Street,
Herston, QLD 4029
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Ethics committee country [1]
299961
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Australia
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Date submitted for ethics approval [1]
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21/03/2018
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Approval date [1]
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14/09/2018
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Ethics approval number [1]
299961
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ERM ID: 40169
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Summary
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.
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Trial website
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Dr Charles Lin
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Address
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Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street,
Herston, QLD 4029
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Country
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Australia
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Phone
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+61 7 3646 7687
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Fax
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+61 7 3252 2746
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Email
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[email protected]
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Contact person for public queries
Name
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Dr Charles Lin
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Address
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Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street,
Herston, QLD 4029
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Country
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Australia
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Phone
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+61 7 3646 7687
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Fax
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+61 7 3252 2746
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Email
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[email protected]
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Contact person for scientific queries
Name
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Dr Charles Lin
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Address
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Cancer Care Services
Royal Brisbane and Women's Hospital
Butterfield Street,
Herston, QLD 4029
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Country
82096
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Australia
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Phone
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+61 7 3646 7687
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Fax
82096
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+61 7 3252 2746
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Email
82096
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[email protected]
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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
Source
Title
Year of Publication
DOI
Embase
A prospective study investigating the efficacy and toxicity of definitive ChemoRadiation and ImmunOtherapy (CRIO) in locally and/or regionally advanced unresectable cutaneous squamous cell carcinoma.
2021
https://dx.doi.org/10.1186/s13014-021-01795-5
N.B. These documents automatically identified may not have been verified by the study sponsor.
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