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Trial registered on ANZCTR


Registration number
ACTRN12621000991819
Ethics application status
Approved
Date submitted
20/05/2021
Date registered
28/07/2021
Date last updated
28/07/2021
Date data sharing statement initially provided
28/07/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Feasibility of in-vitro testing of chemosensitivity in head and neck carcinoma
Scientific title
A Feasibility Trial of Patient Derived Cell Culture (PDCC) Chemosensitivity in Head and Neck Carcinoma (HNC)
Secondary ID [1] 304265 0
Nil known
Universal Trial Number (UTN)
Trial acronym
PDCCiHNC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Head and Neck Carcinoma 321989 0
Condition category
Condition code
Cancer 319708 319708 0 0
Head and neck

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The objective of this study is to assess the feasibility of performing in vitro chemosensitivity testing, relaying the information back to the treating clinician in a timely manner and using the results in real-time to guide systemic therapy for patients with recurrent or metastastatic head and neck carcinoma (RMHNC).

After the patient signs the consent form for tumour tissue banking, a biopsy/ definitive surgery will be done. The tissues obtained will then be used to derive cell lines and different drugs will be tested on those tissues. The timeline from obtaining tissue to drug response data will be 12 weeks. The treating clinician will be provided a list of the top 3-5 drugs recommended for the patient's cancer. This will be conveyed to the patient and chemotherapy/ target therapy will be administered to patients with their consent. Routine patient record review will be done and clinical/ radiological response observed using RECIST 1.1 criteria will determine whether to continue or withdraw the drug.

The following list is of the drugs that will be tested on the patient derived cell lines. These will be ranked from most sensitive to least sensitive and given to the treating clinician to relay to the patient. All of these drugs are used in routine clinical practice and can be found on the eviQ database:
Carboplatin
Cisplatin
Docetaxel
Doxorubicin
Etoposide
5-Fluorouracil
Gemcitabine
Methotrexate
Paclitaxel
Pemetrexed
Vinorelbine

The following list is of drugs that will be tested as part of an exploratory analysis, but will not be recommended to the patient:
Ceralasertib AZD6738
Dactolisib BEZ235
Tramatenib
Vistusertib
Chloroquine
Itraconazole
Crizotinib
Dasatinib
Erlotinib
Ruxolitinib
Sorafenib
Erlotinib
Palbociclib
Intervention code [1] 320602 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327582 0
A composite primary outcome of determining the proportion of cases in which it is possible to generate patient derived cell lines by audit of study database, perform chemosensitivity testing and providing the results of this to the treating clinician within 12 weeks via data linkage to medical records
Timepoint [1] 327582 0
1 year post-enrolment
Secondary outcome [1] 395732 0
Rate of utilisation of in-vitro chemosensitivity data by the treating clinician. This will be assessed by patient record reviews and compiled.
Timepoint [1] 395732 0
1 year post-enrolment
Secondary outcome [2] 395733 0
Response / tumour progression, assessed in accordance with RECIST 1..1 criteria
Timepoint [2] 395733 0
1 year post-commencement of chemotherapy
Secondary outcome [3] 395734 0
Progression free survival assessed by treating clinician
Timepoint [3] 395734 0
At the time of recurrence and next line of therapy
Secondary outcome [4] 396834 0
Overall survival
Timepoint [4] 396834 0
Overall survival assessed by treating clinician

Eligibility
Key inclusion criteria
- Age equal to 18 years old
- Histological or cytological diagnosis of head and neck carcinoma (HNC)
- Locally advanced, recurrent or metastatic disease that is thought to have a high probability of treatment failure with standard techniques
a. High risk resectable HNC (primary and / or nodal metastases) with sufficient tissue accessible for culture without compromising pathological analysis of the specimen.
b. Unresectable HNC (primary or metastatic) with sufficient tissue accessible for culture via open biopsy or core biopsy.
- ECOG performance status less than or equal to 2.
- Prior systemic therapy is permitted if given more than 6 months prior to study entry in one of the following situations:
• as neoadjuvant therapy;
• as part of definitive chemo-radiotherapy for locally advanced disease; or
• as a component of adjuvant post-surgical treatment.
- Adequate haematological function:
• Hb more than or equal to 90 g/L
• Platelet count more than or equal to 100
• Neutrophil count more than or equal to 1.5
- Adequate biochemical function
• Creatinine less than 1.5 times the upper limit of normal
• AST and / or ALT less than 3 times the upper limit of normal (less than 5 times the upper limit of normal if hepatic metastases present)
• Bilirubin less than 1.5 times the upper limit of normal (unless known Gilberts disease, in which case less than 3 times the upper limit of normal)
- Provision of informed consent.
- Female subjects of childbearing potential have a negative pregnancy test at screening and on Day 1 prior to dosing.
- Female subjects of childbearing potential who are willing to use a highly effective method of birth control or who are surgically sterile or abstain from heterosexual activity for the course of the study and for 6 months after last dose of systemic anticancer therapy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Prior therapy for recurrent and metastatic head and neck squamous cell carcinoma other than as outlined in the inclusion criteria
- Inability to attend for follow up
- Presence of a significant comorbidity that would preclude the use of chemotherapy
- Known active Hepatitis B or C infection or HIV infection

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
1. DNA sequencing results
- Variant calling will be performed after deducting the germline and normal variants observed in the matched control and normal samples, using established bioinformatics pipelines.
2. RNA sequencing results
- The expression of somatic variants identified from the DNA sequencing data will be analysed, using a variety of tools including but not limited to MaxEntScan and MutSigNC

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
23/08/2021
Actual
Date of last participant enrolment
Anticipated
16/05/2022
Actual
Date of last data collection
Anticipated
15/05/2023
Actual
Sample size
Target
60
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 19503 0
The Chris O’Brien Lifehouse - Camperdown
Recruitment postcode(s) [1] 34097 0
2050 - Camperdown

Funding & Sponsors
Funding source category [1] 308643 0
Government body
Name [1] 308643 0
Sydney Local Health District
Country [1] 308643 0
Australia
Primary sponsor type
Hospital
Name
Chris O'Brien Lifehouse
Address
119-143 Missenden Road, Camperdown 2050, NSW
Country
Australia
Secondary sponsor category [1] 309522 0
None
Name [1] 309522 0
Address [1] 309522 0
Country [1] 309522 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308569 0
St Vincent's Hospital Human Research Ethics
Ethics committee address [1] 308569 0
390 Victoria Street
Darlinghurst NSW 2010
Ethics committee country [1] 308569 0
Australia
Date submitted for ethics approval [1] 308569 0
26/11/2020
Approval date [1] 308569 0
02/12/2020
Ethics approval number [1] 308569 0
2020/ETH01283

Summary
Brief summary
The aim of this study is to investigate the feasibility of personalising chemotherapy treatment using in-vitro (in the laboratory) testing of patient-derived cells to guide the choice of chemotherapy for patients with head and neck carcinoma.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, have been diagnosed with locally advanced, recurrent, or metastatic head and neck carcinoma, and are thought to have a high probability of treatment failure with standard techniques.

Study details
All participants will undergo definitive surgery and the biopsy will be transported to anatomical pathology where tissue assessment will be done in great detail, followed by transfer of tissues to either Macquarie university or Garvan Institute where cell lines will be developed, tested for tumor markers, tested for chemotherapeutic drugs including target therapy, and then based on an algorithm derived drug recommendation, the clinician will be informed. The patient will be informed of the results and depending on whether they choose to proceed with treatment, they will be assessed for progression of disease using RECIST 1.1 criteria.

It is hoped that this study may demonstrate that testing the sensitivity of patient-derived cancer cells to guide choice of chemotherapy agent prior to their administration will reduce tumour progression and improve survival in patients with head and neck carcinoma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 111174 0
Prof Ruta Gupta
Address 111174 0
Royal Prince Alfred Hospital/ NSW Health Pathology
Missenden Road Building 77
Camperdown NSW 2050
Country 111174 0
Australia
Phone 111174 0
+61 29515 8076
Fax 111174 0
Email 111174 0
[email protected]
Contact person for public queries
Name 111175 0
Ruta Gupta
Address 111175 0
Royal Prince Alfred Hospital/ NSW Health Pathology
Missenden Road Building 77
Camperdown NSW 2050
Country 111175 0
Australia
Phone 111175 0
+61 29515 8076
Fax 111175 0
Email 111175 0
[email protected]
Contact person for scientific queries
Name 111176 0
Jonathan Clark
Address 111176 0
Level 4, Head and Neck Department
Chris O'Brien Lifehouse
119-143 Missenden Road,
Camperdown NSW 2050
Country 111176 0
Australia
Phone 111176 0
+61 285140268
Fax 111176 0
Email 111176 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Not available at this point, may consider making it available when there is more data to consider


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11726Ethical approval    382029-(Uploaded-27-07-2021-14-16-46)-Study-related document.pdf
11727Study protocol    382029-(Uploaded-20-05-2021-15-29-38)-Study-related document.docx



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.