Clinical Trials /

Intratumoral Microdosing of TAK-981 in Head and Neck Cancer

NCT04065555

Description:

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.

Related Conditions:
  • Head and Neck Carcinoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intratumoral Microdosing of TAK-981 in Head and Neck Cancer
  • Official Title: Evaluation of TAK-981 and TAK-981 Combinations Following Intratumoral CIVO® Microdosing in Patients With Head and Neck Cancer

Clinical Trial IDs

  • ORG STUDY ID: PBI-TAK-01
  • NCT ID: NCT04065555

Conditions

  • Head and Neck Cancer

Interventions

DrugSynonymsArms
TAK-981CIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab
CetuximabERBITUXCIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab
AvelumabBavencioCIVO Microdose Injection of TAK-981, Cetuximab, and Avelumab

Purpose

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.

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. 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 percutaneously 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.
    

Trial Arms

NameTypeDescriptionInterventions
CIVO Microdose Injection of TAK-981, Cetuximab, and AvelumabExperimentalPatients 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 and percutaneously 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.
  • TAK-981
  • Cetuximab
  • Avelumab

Eligibility 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 primary cancers of the head and neck.

          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 or effaced metastatic lymph node) ≥ 2 cm in the
             shortest diameter that is accessible for ultrasound-guided percutaneous CIVO injection
             and for which there is a planned surgical intervention. Treatment plan may include
             adjuvant radiation or chemotherapy.

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

          7. Acceptable bone marrow, renal, and hepatic function based upon screening lab tests as
             demonstrated by the following:

               -  Absolute neutrophil count ≥ 1,000 cells/μL

               -  Platelet count ≥ 75,000 per μL

               -  Hemoglobin ≥ 10g/dL

               -  Creatinine ≤ 1.5x the age-adjusted upper limit of normal

               -  Total bilirubin ≤ 1.5x the upper limit of normal (with the exception of patients
                  with Gilbert's syndrome for which higher bilirubin values would be acceptable
                  provided the patient has normal liver function)

               -  AST (Aspartate Aminotransferase)/SGOT (Serum Glutamate Oxaloacetate Transaminase)
                  and ALT (Alanine Aminotransferase)/SGPT (Serum Glutamate Pyruvate Transaminase) ≤
                  2.5x the upper limit of normal

          8. Female patients who:

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

               -  Are surgically sterile, OR

               -  If they are of childbearing potential, agree to practice two effective methods of
                  contraception, at the same time, from the time of signing of the informed consent
                  through four months after the tumor injection procedure, OR agree to completely
                  abstain from heterosexual intercourse.

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

          -  Agree to practice effective barrier contraception during the entire study treatment
             period through four months after the tumor injection procedure, OR

          -  Agree to completely abstain from heterosexual intercourse.

        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, fibrosis, or treatment-induced tissue changes.
             Lesions that have received neoadjuvant radiation therapy may lack sufficient viable
             tumor tissue for CIVO injection procedures.

          2. Patients who have received prior treatment with cetuximab or immune checkpoint
             inhibitors.

          3. Female patients who are both lactating and breastfeeding or have a positive serum
             pregnancy during the screening period or a positive urine pregnancy test on Day 1
             before the tumor injection procedure.

          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 uncontrolled autoimmune diseases requiring treatment.

          6. Patients with human immunodeficiency virus/acquired immune deficiency syndrome
             (HIV/AIDS) with uncontrolled viral load and CD4 (Cluster of Differentiation 4) less
             than 200.

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

          8. Patients with a sensitivity to Captisol.

          9. Use of any of the following ≤ 2 weeks prior to CIVO injection:

               1. Immunosuppressive drugs (e.g., calcineurin inhibitors)

               2. Biological response modifiers for autoimmune disease

               3. Systemic glucocorticoids: oral or parenteral corticosteroids at a dose ≥ 20
                  mg/day prednisone, or equivalent Note: physiologic replacement dosing of steroids
                  (≤ 3mg/m2/d prednisone or equivalent), low-dose corticosteroids for dye allergies
                  prior to staging scans or use in anti-emetic prophylaxis for patients undergoing
                  chemotherapy, or topical steroids, are allowed

               4. Hematopoietic growth factors

               5. Anticoagulants such as warfarin or low-molecular-weight heparin
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Quantification of Biomarker-Positive and Biomarker-Negative Cells
Time Frame:1 or 3 days after microdose injection
Safety Issue:
Description:Quantification of fraction of cells positive for apoptosis and drug target engagement biomarkers around injected drugs. Immunohistochemistry (IHC) assessment will be performed to determine if there is a difference in responses caused by TAK-981 injected singly or in combination with either cetuximab or avelumab.

Secondary Outcome Measures

Measure:Number of Patients with Adverse Events Related to Pain
Time Frame:Up to 28 days after microdose injection
Safety Issue:
Description:Relationship of AE to study drug or CIVO device will be determined using an AE Relatedness Grading System.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Presage Biosciences

Trial Keywords

  • precision oncology
  • intratumoral microdosing
  • microdose injection
  • microinjection
  • microdosing
  • in vivo oncology
  • in vivo drug sensitivity
  • tumor microenvironment
  • multiplexed immunohistochemistry
  • HNSCC
  • SCCHN

Last Updated

September 1, 2020