Immune System Diseases

All Conditions

Neoplasms

Hypersensitivity

Head and Neck Neoplasms

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Cetuximab

Avelumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected one day (Cohort 1) or three days (Cohort 2) 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-981, cetuximab, avelumab, TAK-981 combined with cetuximab, or TAK-981 combined with avelumab. 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. Approximately six patients will be assigned to each time point cohort. Cohort assignment is not sequential and will be selected by the Investigator based on clinic logistics and patient scheduling. Should one cohort fill in advance of the other, sites will be directed by Presage to enroll patients into the second cohort only.

Intratumoral microdose injection by the CIVO device.

TAK-981

TAK-981 + Cetuximab

TAK-981 + Avelumab

Medical Director

This is a multi-center, single arm, open-label, multi-agent, localized pharmacodynamic biomarker Phase 0 trial designed to study the biological effects within the tumor microenvironment of TAK-981 and TAK-981 combined with cetuximab or avelumab when administered intratumorally in microdose quantities via the CIVO device. CIVO stands for comparative in vivo oncology.

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. In this Phase 0 intratumoral microdosing study in human patients with localized or metastatic primary tumors of the head and neck (who will be undergoing previously planned tumor and regional nodes dissection), we will evaluate TAK-981's ability to activate innate immune effector cells within the local tumor microenvironment. Additionally, this study will examine TAK-981 in combination with cetuximab or avelumab to study whether TAK-981 enhances the localized immune responses compared to those of either immunotherapy alone. TAK-981 singly and in combination with cetuximab or avelumab will be delivered intratumorally in subtherapeutic microdose quantities via CIVO.

The CIVO device penetrates solid tumors and 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. At the time of the planned surgical intervention (one or three 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. 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.

Intratumoral Microdosing of TAK-981 in Head and Neck Cancer

Evaluation of TAK-981 and TAK-981 Combinations Following Intratumoral CIVO® Microdosing in Patients With Head and Neck Cancer

Quantification of biomarker-positive and biomarker-negative cells will be performed within the tumor microenvironment around each of the injection sites of each resected patient sample by IHC and ISH. An aggregate analysis of this quantification may be done across patient samples to evaluate trends in tumor response. List of biomarkers evaluated may include biomarkers for cell death (e.g. cleaved caspase 3), T-cells (e.g. CD3, CD8/Granzyme B), and natural killer (NK) or myeloid cells (e.g. CD56/Granzyme B, CD86, CD68).

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

Takeda

Presage Biosciences

Rare Diseases

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Anti-Infective Agents

Dermatologic Agents

Gemcitabine

Nivolumab

Pembrolizumab

Docetaxel

Atezolizumab

Doxorubicin

Liposomal doxorubicin

Aldesleukin

Durvalumab

Bortezomib

Ipilimumab

Coal Tar

Interferons

Interferon-alpha

Trabectedin

Interferon-gamma

Entrectinib

Interferon alpha-2

Olaratumab

Antimetabolites

Tubulin Modulators

Antimitotic Agents

Immune Checkpoint Inhibitors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Antiviral Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Protein Kinase Inhibitors

Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected 4 to 72 hours prior to surgery using the CIVO device. Minute volumes (up to 8.3 microliters) of saline (negative control) or microdoses of anti-cancer agents will be percutaneously injected in a columnar fashion through each of 8 needles into a single enlarged solid tumor.

This is a feasibility study in patients with localized or metastatic soft tissue sarcoma undergoing surgery to determine how sarcoma in situ responds to injected microdoses of anti-cancer therapeutics.

Multiple drug microinjection

Feasibility of assessing drug response to precise local injection of anti-cancer drugs using Presage's CIVO device in soft tissue sarcoma patients undergoing surgery.

CIVO device

Gary Deutsch, MD

Kenneth Gundle, MD

Seth Pollack, MD

This is a single arm, pilot study designed to test the feasibility of using the CIVO (Comparative In Vivo Oncology) system in patients with soft tissue sarcoma accessible for percutaneous injection. Patients who are scheduled for surgical biopsy or tumor resection surgery will be injected 4 to 72 hours prior to surgery using the CIVO device. Minute volumes (up to 8.3 microliters) of saline (negative control) or microdoses of anti-cancer agents will be percutaneously injected in a columnar fashion through each of 8 needles into a single solid tumor. Following the patient's biopsy surgery or tumor resection surgery, the injected portion and a small uninjected portion will be used to determine the in situ drug response in the tumor. None of the data from this evaluation will be shared with patients or used to make clinical decisions. Study clinicians will have access to the patient's health record for 1 year after the study to monitor patient treatment responses. Such information will be used to help evaluate the correlation between clinical response and tumor response assessed via CIVO.

Precise Local Injection of Anti-cancer Drugs Using Presage's CIVO Device in Soft Tissue Sarcoma

Feasibility of Assessing Drug Response to Precise Local Injection of Anti-cancer Drugs Using Presage's CIVO Device in Soft Tissue Sarcoma Patients Undergoing Surgery.

Analysis will be performed to determine if there is a difference in responses caused by each drug versus the vehicle control

Relationship of AE to study device or study procedure will be determined using an AE Relatedness Grading System.

Analysis will be performed for fraction of cells positive for apoptosis and drug target engagement biomarkers

Fred Hutchinson Cancer Center

University of Washington

Northwell Health

Oregon Health and Science University

Blood and Lymph Conditions

Lymphoma

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphosarcoma

Antirheumatic Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Bendamustine Hydrochloride

Rituximab

Vincristine

Prednisolone

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Multiple drug microinjection with locally injected rituximab, vincristine, doxorubicin, bendamustine, prednisolone, or a combination of them

Multiple drug microinjection: rituximab, vincristine, doxorubicin, bendamustine, prednisolone or a combination of them

Oliver W Press, MD, PhD

Many cancer patients are prescribed drugs to which their cancer is already resistant - and thus suffer toxicity with no potential for benefit. Previous attempts to assess chemoresistance or sensitivity in vitro have failed. This is a feasibility study in human patients with newly diagnosed or recurrent lymphoma to determine how human cancerous lymph nodes in situ respond to standard of care therapeutics precisely microinjected with the CIVO(tm) microdosing system.

Feasibility of Assessing Lymphoma Response to Precise Local Injection of Candidate Chemotherapy Agents

Feasibility of Assessing Lymphoma Response to Precise Local Injection of Candidate Chemotherapy Agents Using the CIVO(tm) Microdosing System

National Institutes of Health (NIH)

National Cancer Institute (NCI)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Intratumoral Microdosing of TAK-981 in Head and Neck Cancer	NCT04065555	Head and Neck C...	TAK-981 Cetuximab Avelumab TAK-981 + Cetux... TAK-981 + Avelu...	18 Years -	Presage Biosciences
Precise Local Injection of Anti-cancer Drugs Using Presage's CIVO Device in Soft Tissue Sarcoma	NCT03056599	Soft Tissue Sar...	Multiple drug m... CIVO device	18 Years -	Presage Biosciences
Feasibility of Assessing Lymphoma Response to Precise Local Injection of Candidate Chemotherapy Agents	NCT01831505	Lymphoma	Multiple drug m...	18 Years -	Presage Biosciences
Intratumoral Microdosing of TAK-981 in Head and Neck Cancer	NCT04065555	Head and Neck C...	TAK-981 Cetuximab Avelumab TAK-981 + Cetux... TAK-981 + Avelu...	18 Years -	Presage Biosciences

Spots Global Cancer Trial Database for microinjection