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Trial record 2 of 3 for:    CIVO | Soft Tissue Sarcoma

Phase 0 Master Protocol for CIVO Intratumoral Microdosing of Anti-Cancer Therapies

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ClinicalTrials.gov Identifier: NCT04541108
Recruitment Status : Recruiting
First Posted : September 9, 2020
Last Update Posted : June 4, 2021
Sponsor:
Collaborators:
Bristol-Myers Squibb
Takeda
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Presage Biosciences

Brief Summary:
This is a multi-center, open-label Phase 0 Master Protocol designed to study the localized pharmacodynamics (PD) of anti-cancer therapies within the tumor microenvironment (TME) when administered intratumorally in microdose quantities via the CIVO device in patients with surface accessible solid tumors 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.

Condition or disease Intervention/treatment Phase
Solid Tumor Drug: BMS-986299 Biological: Relatlimab Biological: Ipilimumab Biological: Nivolumab Combination Product: Ipilimumab + Nivolumab Combination Product: Relatlimab + Nivolumab Combination Product: BMS-986299 + Nivolumab Drug: TAK-676 Drug: Carboplatin Drug: 5-FU Drug: Paclitaxel Combination Product: TAK-676 + Carboplatin Combination Product: Carboplatin + Paclitaxel Combination Product: Carboplatin + 5-FU Combination Product: TAK-676 + Carboplatin + 5-FU Combination Product: TAK-676 + Carboplatin + Paclitaxel Biological: Pembrolizumab Combination Product: MK-0482 + Pembrolizumab Combination Product: MK-4830 + Pembrolizumab Early Phase 1

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 tumor. Tumor responses to cancer treatments are highly context-specific and often involve complex interactions between the anti-cancer therapy, genetically diverse tumor cells, and a heterogeneous TME. This complexity is rarely modeled accurately in preclinical translational models of cancer. By utilizing intratumoral 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 tumor 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 tumor tissue, hypotheses can be tested earlier in the drug development process, consistent with the goals of the 2006 FDA Exploratory IND Guidance for Industry.

The CIVO device penetrates solid tumors 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 tumor 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 tumor tissue is then excised and tumor responses are assessed via histological staining of tumor 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Basic Science
Official Title: A Phase 0 Master Protocol Using the CIVO® Platform to Evaluate Intratumoral Microdoses of Anti-Cancer Therapies in Patients With Solid Tumors
Estimated Study Start Date : June 2021
Estimated Primary Completion Date : December 2031
Estimated Study Completion Date : December 2031

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BMS-986299, Relatlimab, Ipilimumab, & Nivolumab
Patients who are scheduled for surgical biopsy or tumor 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 dextrose) or subtherapeutic microdoses of BMS-986299, relatlimab, ipilimumab as single agents or combined with nivolumab. Each microdose is simultaneously injected in a columnar fashion through each of 8 or 5 needles (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node.
Drug: BMS-986299
Intratumoral microdose injection by the CIVO device.

Biological: Relatlimab
Intratumoral microdose injection by the CIVO device.
Other Name: BMS-986016

Biological: Ipilimumab
Intratumoral microdose injection by the CIVO device.
Other Names:
  • Yervoy
  • BMS-734016
  • MDX-010

Biological: Nivolumab
Intratumoral microdose injection by the CIVO device.
Other Names:
  • Opdivo
  • BMS-936558

Combination Product: Ipilimumab + Nivolumab
Intratumoral microdose injection by the CIVO device.

Combination Product: Relatlimab + Nivolumab
Intratumoral microdose injection by the CIVO device.

Combination Product: BMS-986299 + Nivolumab
Intratumoral microdose injection by the CIVO device.

Experimental: TAK-676, Carboplatin, 5-FU, & Paclitaxel
Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected at least four hours to up to four 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) or subtherapeutic microdoses of TAK-676, carboplatin, 5-fluorouracil (5-FU), or paclitaxel as single agents or in combination. Each microdose is simultaneously injected in a columnar fashion through each of 8, 5, or 3 needles (in a device configuration determined by tumor dimensions) into a single solid tumor or effaced metastatic lymph node.
Drug: TAK-676
Intratumoral microdose injection by the CIVO device.

Drug: Carboplatin
Intratumoral microdose injection by the CIVO device.
Other Name: Paraplatin

Drug: 5-FU
Intratumoral microdose injection by the CIVO device.
Other Name: Adrucil

Drug: Paclitaxel
Intratumoral microdose injection by the CIVO device.
Other Name: Taxol

Combination Product: TAK-676 + Carboplatin
Intratumoral microdose injection by the CIVO device.

Combination Product: Carboplatin + Paclitaxel
Intratumoral microdose injection by the CIVO device.

Combination Product: Carboplatin + 5-FU
Intratumoral microdose injection by the CIVO device.

Combination Product: TAK-676 + Carboplatin + 5-FU
Intratumoral microdose injection by the CIVO device.

Combination Product: TAK-676 + Carboplatin + Paclitaxel
Intratumoral microdose injection by the CIVO device.

Experimental: MK-0482, MK-4830, & Pembrolizumab
Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected two to four 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) or subtherapeutic microdoses of pembrolizumab as a single agent or in combination with MK-0482 or MK-4830. Each microdose is simultaneously injected in a columnar fashion through each of 8 needles into a single solid tumor or effaced metastatic lymph node.
Biological: Pembrolizumab
Intratumoral microdose injection by the CIVO device.
Other Names:
  • Keytruda
  • MK-3475

Combination Product: MK-0482 + Pembrolizumab
Intratumoral microdose injection by the CIVO device.

Combination Product: MK-4830 + Pembrolizumab
Intratumoral microdose injection by the CIVO device.




Primary Outcome Measures :
  1. Quantification of Cell Death and Immune Cell Biomarkers by IHC and In-Situ Hybridization [ Time Frame: 4 hours-7 days after microdose injection ]
    Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor 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 tumor 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, tumor necrosis factor alpha, interferon gamma-induced protein 10).


Secondary Outcome Measures :
  1. Number of Patients with Adverse Events [ Time Frame: Up to 28 days after microdose injection ]
    Relationship of AE to study drug(s) or CIVO device will be determined using an AE Relatedness Grading System.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Inclusion 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 tumors] 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 tumor, recurrent tumor, 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 my 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.

Exclusion Criteria:

  1. Tumors or effaced nodes that are anticipated by the Investigator to lack a sufficient volume of viable tumor 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, or fibrosis.
  2. Patients who have received neoadjuvant therapy associated with the surgical intervention described in Inclusion Criterion #5.
  3. Tumors near or involving critical structures for which, in the opinion of the treating clinician, injection would pose undue risk to the patient.
  4. Female patients who are:

    • Both lactating and breastfeeding, OR
    • Have a positive β-subunit human chorionic gonadotropin (β-hCG) pregnancy test at screening verified by the Investigator.
  5. 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.
  6. Patients with a history of concurrent second cancers requiring active, ongoing systemic treatment.
  7. Patients with active autoimmune diseases requiring treatment.
  8. Patients with known human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) with uncontrolled viral load and CD4 less than 200, or known chronic hepatitis B/C.
  9. Patients that have received a live vaccine within 4 weeks of the baseline/screening visit.
  10. 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.
    3. Hematopoietic growth factors.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04541108


Contacts
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Contact: Presage Biosciences 800-530-5404 clinops@presagebio.com

Locations
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United States, Louisiana
LSU Health Sciences Center - Shreveport Recruiting
Shreveport, Louisiana, United States, 71115
Contact: Research Coordinator         
United States, North Carolina
Wake Forest Baptist Health Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Research Coordinator         
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Research Coordinator         
Sponsors and Collaborators
Presage Biosciences
Bristol-Myers Squibb
Takeda
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Presage Biosciences
Publications:

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Responsible Party: Presage Biosciences
ClinicalTrials.gov Identifier: NCT04541108    
Other Study ID Numbers: PBI-MST-01
First Posted: September 9, 2020    Key Record Dates
Last Update Posted: June 4, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Presage Biosciences:
sarcoma
CIVO
soft tissue sarcoma
HNSCC
SCCHN
lymphoma
breast adenocarcinoma
melanoma
intratumoral microdosing
microdose injection
microdosing
in vivo oncology
in vivo drug sensitivity
tumor microenvironment
multiplexed immunohistochemistry
head and neck cancer
pharmacodynamic biomarkers
master protocol
precision oncology
Additional relevant MeSH terms:
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Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Pembrolizumab
Nivolumab
Fluorouracil
Ipilimumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Antimetabolites
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs