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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04891718




Registration number
NCT04891718
Ethics application status
Date submitted
13/05/2021
Date registered
18/05/2021
Date last updated
8/07/2022

Titles & IDs
Public title
CIVO Intratumoural Microdosing of Anti-Cancer Therapies in Australia
Scientific title
A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoural Microdoses of Anti-Cancer Therapies in Patients With Solid Tumours
Secondary ID [1] 0 0
PBI-MST-02
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumour 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MVC-101
Other interventions - Nivolumab
Combination Product - MVC-101 + Nivolumab

Experimental: MVC-101 and Nivolumab - Patients with HNSCC who are scheduled for surgical biopsy or tumour resection surgery will be injected at least four hours to up to three days prior to surgery using the CIVO device. Each needle of the CIVO device will deliver up to 8.3 microliters of solution, including a vehicle control (sterile saline and solution stabilizer), a pre-cleaved/pre-activated drug control (cMVC-101), MVC-101 (the prodrug), or nivolumab as single agents or as combinations. Each drug will be delivered in subtherapeutic microdoses, and each microdose is simultaneously injected in a columnar fashion through each of 3, 5, or 8 needles (in a device configuration determined by tumour dimensions) into a single solid tumour or effaced metastatic lymph node.


Other interventions: MVC-101
Intratumoural microdose injection by the CIVO device.

Other interventions: Nivolumab
Intratumoural microdose injection by the CIVO device.

Combination Product: MVC-101 + Nivolumab
Intratumoural microdose injection by the CIVO device.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Combination Product
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Quantification of Cell Death and Immune Cell Biomarkers by IHC and In-Situ Hybridization
Timepoint [1] 0 0
4 hours-7 days after microdose injection
Secondary outcome [1] 0 0
Number of Patients with Adverse Events
Timepoint [1] 0 0
Up to 28 days after microdose injection

Eligibility
Key inclusion criteria
*This list is representative of study inclusion/exclusion criteria. Each substudy may
include variations on these criteria.



1. Ability and willingness to comply with the study's visit and assessment schedule.

2. Male or female = 18 years of age at Visit 1 (Screening).

3. Pathologic diagnosis of [solid tumours] indicated in the relevant substudy(ies).

4. Ability and willingness to provide written informed consent. Voluntary written consent
must be given before performance of any study related procedure not part of standard
medical care, with the understanding that consent may be withdrawn by the patient at
any time without prejudice to future medical care.

5. At least one lesion (primary tumour, recurrent tumour, or effaced metastatic lymph
node) = 2 cm in the shortest diameter that is surface accessible for CIVO injection
that may be guided by ultrasound if appropriate and for which there is a planned
surgical intervention. Treatment plan may include adjuvant radiation or chemotherapy
and patients should have no medical contraindication to surgery.

6. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

7. Female patients who:

- Are postmenopausal for at least one year before the screening visit, OR

- Are surgically sterile, OR

- Are of childbearing potential who agree to practice a highly effective method of
contraception from the time of signing the Informed Consent Form (ICF) and during
study participation OR agree to completely abstain from heterosexual intercourse.

- Agree to refrain from donating ova during study participation.

Male patients, even if surgically sterile (i.e., status post-vasectomy), who:

- Agree to practice effective barrier contraception from the time of signing the ICF and
during study participation OR agree to completely abstain from heterosexual
intercourse.

- Agree to refrain from donating sperm during study participation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Tumours or effaced nodes that are anticipated by the Investigator to lack a sufficient
volume of viable tumour tissue (based on available pre-operative imaging,
pre-injection ultrasound imaging, or pathology reports) for CIVO injection due to
size, location, necrosis, cysts, excessive stroma, fibrosis, or treatment-induced
tissue changes.

2. Tumours near or involving critical structures for which, in the opinion of the
treating clinician, injection would pose undue risk to the patient.

3. Female patients who are:

- Breastfeeding

- Have a positive ß-subunit human chorionic gonadotropin (ß-hCG) pregnancy test at
screening verified by the Investigator.

4. Any uncontrolled intercurrent illness, condition, serious medical or psychiatric
illness, or circumstance that, in the opinion of the Investigator, could interfere
with adherence to the study's procedures or requirements, or otherwise compromise the
study's objectives.

5. Patients with a history of concurrent second cancers requiring active, ongoing
systemic treatment.

6. Patients with active autoimmune diseases requiring treatment.

7. Patients that have received a live vaccine within 4 weeks of the baseline/screening
visit.

8. Use of any of the following = 2 weeks prior to CIVO injection:

1. Chronic systemic immunosuppressive therapy or corticosteroids (e.g., prednisone
or equivalent exceeding a total dose of 140 mg over the last 14 days).
Intranasal, inhaled, topical, or local corticosteroid injections (e.g.,
intra-articular injection), or steroids as premedication for hypersensitivity
reactions (e.g., computed tomography [CT] scan premedication) are exceptions to
this criterion.

2. Biological response modifiers for treatment of active autoimmune disease.

Study design
Purpose of the study
Basic Science
Allocation to intervention
N/A
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
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
5/06/2022
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Chris O'Brien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [3] 0 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2500 - Wollongong
Recruitment postcode(s) [3] 0 0
5042 - Bedford Park

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Presage Biosciences
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Takeda
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a multi-center, open-label Phase 0 Master Protocol in Australia designed to study the
localized pharmacodynamics (PD) of anti-cancer therapies within the tumour microenvironment
(TME) when administered intratumourally in microdose quantities via the CIVO device in
patients with surface accessible solid tumours for which there is a scheduled surgical
intervention. CIVO stands for Comparative In Vivo Oncology. Multiple substudies will include
specified investigational agents and combinations to be evaluated.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04891718
Trial related presentations / publications
Gundle KR, Deutsch GB, Goodman HJ, Pollack SM, Thompson MJ, Davis JL, Lee MY, Ramirez DC, Kerwin W, Bertout JA, Grenley MO, Sottero KHW, Beirne E, Frazier J, Dey J, Ellison M, Klinghoffer RA, Maki RG. Multiplexed Evaluation of Microdosed Antineoplastic Agents In Situ in the Tumor Microenvironment of Patients with Soft Tissue Sarcoma. Clin Cancer Res. 2020 Aug 1;26(15):3958-3968. doi: 10.1158/1078-0432.CCR-20-0614. Epub 2020 Apr 16.
Klinghoffer RA, Bahrami SB, Hatton BA, Frazier JP, Moreno-Gonzalez A, Strand AD, Kerwin WS, Casalini JR, Thirstrup DJ, You S, Morris SM, Watts KL, Veiseh M, Grenley MO, Tretyak I, Dey J, Carleton M, Beirne E, Pedro KD, Ditzler SH, Girard EJ, Deckwerth TL, Bertout JA, Meleo KA, Filvaroff EH, Chopra R, Press OW, Olson JM. A technology platform to assess multiple cancer agents simultaneously within a patient's tumor. Sci Transl Med. 2015 Apr 22;7(284):284ra58. doi: 10.1126/scitranslmed.aaa7489.
Frazier JP, Bertout JA, Kerwin WS, Moreno-Gonzalez A, Casalini JR, Grenley MO, Beirne E, Watts KL, Keener A, Thirstrup DJ, Tretyak I, Ditzler SH, Tripp CD, Choy K, Gillings S, Breit MN, Meleo KA, Rizzo V, Herrera CL, Perry JA, Amaravadi RK, Olson JM, Klinghoffer RA. Multidrug Analyses in Patients Distinguish Efficacious Cancer Agents Based on Both Tumor Cell Killing and Immunomodulation. Cancer Res. 2017 Jun 1;77(11):2869-2880. doi: 10.1158/0008-5472.CAN-17-0084. Epub 2017 Mar 31.
Dey J, Kerwin WS, Grenley MO, Casalini JR, Tretyak I, Ditzler SH, Thirstrup DJ, Frazier JP, Pierce DW, Carleton M, Klinghoffer RA. A Platform for Rapid, Quantitative Assessment of Multiple Drug Combinations Simultaneously in Solid Tumors In Vivo. PLoS One. 2016 Jun 30;11(6):e0158617. doi: 10.1371/journal.pone.0158617. eCollection 2016.
Moreno-Gonzalez A, Olson JM, Klinghoffer RA. Predicting responses to chemotherapy in the context that matters - the patient. Mol Cell Oncol. 2015 Jun 10;3(1):e1057315. doi: 10.1080/23723556.2015.1057315. eCollection 2016 Jan.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Presage Biosciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04891718