CompletedPhase 1ACTRN12618000675224

INB03 for patients with metastatic cancer with increased inflammatory biomarkers in peripheral blood

Phase 1 open-label, dose escalation study of INB03 in patients with metastatic cancer with increased inflammatory biomarkers in peripheral blood

Sponsor

CTI Clinical Trial and Consulting Services Australia Pty Ltd

Enrollment

15 participants

Start Date

Aug 21, 2018

Study Type

Interventional

Conditions

solid epithelial tumour Cancer Epithelial Cancer

Summary

The purpose of this study is to determine the safety and tolerability of INB03 in patients with metastatic cancer. Who is it for? You may be eligible for this study if you have epithelial cancer of the lung, breast, upper or lower gastrointestinal tract, kidney, or skin (melanoma only). Study details. All participants will receive INB03 subcutaneously once a week for up to 9 months. There will be three groups who each receive a different dose. As a part of the clinical research study patients will have regular blood tests, physical examinations, will have to complete short questionnaires on their depression, sleep and fatigue. This is first in the human clinical research study and its results will help to determine if INB03 is safe and is tolerated well. Dose of INB03 selected in this study will be used in future study intended for patients with metastatic cancer.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 80 Yearss

Inclusion Criteria25

Subject is greater than or equal to 18 years old, male or female.
Subject has histopathological diagnosis of epithelial cancer and meets the following criteria:
a. Diagnosed with stage 3 or 4 cancer of the lung, breast, upper or lower gastrointestinal
tract, kidney, or skin (melanoma only)
b. Diagnosed with cancer that is unlikely to clinically benefit from any other currently
available therapies.
c. There is no limit to the number of prior therapies allowed.
Subject has an hsCRP >10 mg/L that cannot be attributed to an infection.
Subject has a life expectancy > 4 months in the opinion of the Investigator.
Subject has adequate organ and marrow function (as defined below):
a. Serum creatinine less than or equal to 1.5 X upper limit of normal (ULN), or calculated creatinine clearance greater than or equal to 60 ml/min/1.73m2 as measured by Cockcroft-Gault
b. Aspartate aminotransferase and alanine aminotransferase levels less than or equal to 3 X ULN.
c. Total bilirubin < 1.5 X ULN, unless known diagnosis of Gilbert’s syndrome
d. Absolute neutrophil greater than or equal to 1,500/mm3
e. Platelet count greater than or equal to 50,000/mm3
f. Hemoglobin greater than or equal to 10 mg/dL (transfusion to obtain hemoglobin greater than or equal to 10 mg/dL within 24 hours prior to dosing is allowed)
Subject must be at least 4 weeks from previous therapy (eg, chemotherapy, hormonal therapy,
radiation therapy, immunotherapy and monoclonal antibodies, alternative therapy or
investigational therapeutic agents).
Subjects who have had major surgery must be fully recovered and require a recovery period of greater than or equal to 4 weeks prior to study Screening.
Subject must have an Eastern Cooperative Oncology Group performance status less than or equal to 2.
Subjects who are women of childbearing potential must not be pregnant and breastfeeding. Male and female subjects of childbearing potential must agree to use adequate contraception (barrier method or abstinence) for the duration of study therapy and for 3 months after the last dose of INB03. Any pregnancy that occurs for study participants should be monitored for potential side effects.
a. Women must discontinue any hormonal forms of birth control at least 4 weeks
prior to initiating the study.
Subject, or legal guardian, must be able to understand and voluntarily sign a written informed consent, and are willing and able to comply with the protocol requirements.

Exclusion Criteria17

Subject has sarcoma, haematological cancer or primary cancer of the central nervous system. Patients with brain metastasis from an epithelial cancer are eligible for treatment.
Subject has an active infection. Subjects may become eligible once infection has resolved and they are at least 7 days from completion of antibiotics and hsCRP returned to baseline.
Subject is currently taking concomitant corticosteroids or other immunosuppressive drugs. (Note, inhaled steroids for asthma and chronic obstructive pulmonary disease is accepted)
Subject is currently taking concomitant thalidomide or a tumour necrosis factor (TNF) alpha- inhibitors.
Subject has a resting, room air oxygen partial pressure (PO2) < 90% at Screening.
Subject has impaired cardiac function or clinically significant cardiac disease including the following:
a. New York Heart Association grade III or IV congestive heart failure.
b. Myocardial infarction within the last 6 months prior to dosing with INB03
c. Impaired left ventricular ejection fraction (< 40%) as assessed according to institutional
standards.
Subject has human immunodeficiency virus infection or an active hepatitis C or hepatitis B virus infection.
Subject has any other condition or finding that in the opinion of the PI or Sponsor Medical Monitor may render the subject at excessive risk for treatment complications or may not be able provide evaluable outcome information.
Subject has shown lack of recovery of prior adverse events (AEs) to Grade less than or equal to 1 severity (National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE] v 5.0) (except alopecia) due to therapy administered prior to the initiation of study drug dosing by the time of study Screening. Stable persistent grade 2 peripheral neuropathy may be allowed as determined on a case-by-case basis at the discretion of the PI or Medical Monitor.
Subject has uncontrolled seizures as determined by the PI.
Subject concomitant use of complementary or alternative medication or other agents
(investigational therapeutic agents) will not be allowed without approval of a PI or
sub-investigator. Every effort will be made to maximize subject safety and minimize changes in chronic medications.

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Interventions

The study will consist of 3 dosing cohorts. In each cohort, 3 participants will be treated with once weekly subcutaneous injections of INB03 at a dose of 0.3 (no more than 30 mg), 1.0 (no more than 100 mg) or 3.0 mg/kg (no more than 220 mg or 2 vials of INB03), respectively. INB03 will be administered weekly for 9 months or until disease progression as determined by the PI and/or participant intolerance as determined by the Principal Investigator (PI). However, participants may continue INB03 therapy at any time, including after study end at Month 9, on a compassionate use basis if the attending physician believes the subject is benefiting from the therapy in any way. INB03 will be administered by a study nurse at clinical investigation site from Day 1 till Day 85 visits. At the discretion of the investigator patients may be allowed to self-administer INB03 at home from Month 4 visit onwards. Subjects who undergo home-administration of INB03 will be asked to bring all used, partially used, or unused contains to study staff at each study visit for completion of drug accountability and monitor adherence. All subjects will receive their assigned INB03 dose through Month 3. After all subjects have completed 3 months of therapy, an interim analysis will be conducted and an optimal dose for the Phase 2 trial will be determined by the Data Safety Monitoring Board (DSMB). Further dosing of INB03 after Month 3 may be adjusted to the selected dosage for Phase 2.