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Solid TumourEarly Phase 1NCT04891718

CIVO Intratumoural Microdosing of Anti-Cancer Therapies in Australia

A Early Phase 1 study testing MVC-101, Nivolumab and MVC-101 + Nivolumab in people with Solid Tumour, run by Presage Biosciences at 3 sites in Australia.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumour
What is being tested?
MVC-101, Nivolumab and MVC-101 + Nivolumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesAustralia
Study dates
15 Sep 2021to 5 Jun 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Ability and willingness to comply with the study's visit and assessment schedule.
  • Male or female ≥ 18 years of age at Visit 1 (Screening).
  • Pathologic diagnosis of [solid tumours] indicated in the relevant substudy(ies).
  • 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of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
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  • 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.

Who cannot join

  • 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.
  • Tumours near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
  • Female patients who are:
  • Breastfeeding
  • Have a positive β-subunit human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
  • 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.
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  • Patients with a history of concurrent second cancers requiring active, ongoing systemic treatment.
  • Patients with active autoimmune diseases requiring treatment.
  • Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.
  • Use of any of the following ≤ 2 weeks prior to CIVO injection:
  • 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.
  • Biological response modifiers for treatment of active autoimmune disease.

Trial locations and contacts

3 sites in 1 country.

Australia3 sites
  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

  • Chris O'Brien Lifehouse

    Camperdown, New South Wales, 2050

  • Wollongong Hospital

    Wollongong, New South Wales, 2500

Other trials in Australia

About this study

Official title: A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoural Microdoses of Anti-Cancer Therapies in Patients With Solid Tumours

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.

Read the detailed description

CIVO is a research tool composed of a hand-held single-use sterile injector coupled with fluorescent tracking microspheres called CIVO GLO that mark the sites of drug microdose injection, enabling rapid assessment of multiple oncology drugs or drug combinations simultaneously within a patient's tumour. Tumour responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumour cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoural microdose injections with CIVO in advance of scheduled surgical intervention, this study will evaluate anti-cancer therapies directly in patients each with their own unique tumour genomic profile, intact TME, and immune system functional status. Because the platform delivers microdose amounts of each test agent or combination directly into the patient's tumour tissue, hypotheses can be tested earlier in the drug development process.

The CIVO device penetrates solid tumours and simultaneously delivers subtherapeutic microdoses of up to eight anti-cancer agents or combinations of anti-cancer agents co-injected with CIVO GLO into discrete regions of the tumour as drug columns. At the time of the planned surgical intervention (at least four hours to up to seven days after the CIVO microdose injection), the injected tumour tissue is then excised and tumour responses are assessed via histological staining of tumour cross-sections sampled perpendicular to each injection column. Co-injection with CIVO GLO enables identification of each injection site during resection as well as in tissues stained for analysis. This Phase 0 Master Protocol is aimed at distinguishing promising candidates earlier in the drug development process while also avoiding systemic toxicities associated with typical clinical exposures to these therapies.

Conditions
Solid Tumour
Being tested
MVC-101, Nivolumab, MVC-101 + Nivolumab
Keywords
HNSCC, SCCHN, lymphoma, sarcoma, breast adenocarcinoma, melanoma, intratumoural microdosing, microdose injection, microdosing, in vivo oncology, in vivo drug sensitivity, tumour microenvironment, multiplexed immunohistochemistry, head and neck cancer, pharmacodynamic biomarkers, CIVO, master protocol, precision oncology
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Lymphoma, Sarcoma, Melanoma, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MVC-101Biological

    Also called TAK-186

    Intratumoural microdose injection by the CIVO device.

  • NivolumabBiological

    Also called Opdivo, BMS-936558

    Intratumoural microdose injection by the CIVO device.

  • MVC-101 + NivolumabCombination product

    Intratumoural microdose injection by the CIVO device.

Study groups in NCT04891718
Study groupRoleWhat they receive
MVC-101 and NivolumabExperimentalPatients 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.
Receives: Biological: MVC-101; Biological: Nivolumab; Combination Product: MVC-101 + Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Quantification of Cell Death and Immune Cell Biomarkers by IHC and In-Situ Hybridization

    Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumour microenvironment around each of the injection sites in each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples in each substudy to evaluate trends in tumour response. The biomarkers evaluated may include, but are not limited to biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B, CD4), natural killer (NK)/myeloid cells (e.g. CD56/Granzyme B, CD86, CD68, CD163), and proinflammatory cytokines (e.g., interferon gamma, tumour necrosis factor alpha, interferon gamma-induced protein 10).

    Measured: 4 hours-7 days after microdose injection

Secondary outcomes (1)
  1. Number of Patients with Adverse Events

    Relationship of AE to study drug(s) or CIVO device will be determined using an AE Relatedness Grading System.

    Measured: Up to 28 days after microdose injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2021
  2. Study start15 Sep 2021
  3. Primary completion5 Jun 2022
  4. Study completion5 Jun 2022

Why it stopped: Termination by pharmaceutical sponsor

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
This Master Protocol is designed as an umbrella concept trial for the ongoing evaluation of multiple agents in individual CIVO Phase 0 substudies. Each substudy is considered an "Experimental Arm" with specified investigational agents and combinations to be evaluated. Comparisons will not be made between experimental arms.
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04891718
Sponsor's protocol ID
PBI-MST-02
Status last verified
Jul 2022
First submitted
13 May 2021
Last updated
8 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

    PubMed 32299817
  • 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.

    PubMed 25904742
  • 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.

    PubMed 28364003
  • 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.

    PubMed 27359113
  • 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.

    PubMed 27308571

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing MVC-101, Nivolumab and MVC-101 + Nivolumab in people with Solid Tumour, run by Presage Biosciences at 3 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 8 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Quantification of Cell Death and Immune Cell Biomarkers by IHC and In-Situ Hybridization (time frame: 4 hours-7 days after microdose injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04891718, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2022.

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