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Clinical Trial 21381

Cancer Type: Gastrointestinal Tumor
Study Type: Treatment
NCT#: NCT04421820

Phase: Phase I
Principal Investigator: Kim, Dae Won

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Overview

Study Title

A Phase 1b Dose Escalation Study of BOLD-100 in Combination with FOLFOX Chemotherapy in Patients with Advanced Solid Tumours

Summary

BOLD-100 is an intravenously administered sterile solution containing the ruthenium-based small molecule. BOLD-100 has been shown to preferentially decrease the expression of GRP78 in tumour cells and ER stressed cells when compared to normal cells. BOLD-100 will be combined with cytotoxic FOLFOX chemotherapy in this study, with a dose escalation cohort to ensure tolerability and safety, followed by a cohort expansion phase.

Objective

Primary Part A: Dose Escalation Phase: To assess the safety, tolerability & MTD of standard-of-care (FOLFOX SOC) combination chemotherapy + BOLD-100 in advanced solid tumours Secondary To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours To evaluate the pharmacokinetic and pharmacodynamic parameters of BOLD- 100. To assess potential biomarkers (GRP78) predictive of efficacy Exploratory To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours Primary Part 2: Dose Expansion To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours Secondary To assess the safety, tolerability & MTD of SOC combination chemotherapy + BOLD-100 in advanced solid tumours To evaluate the pharmacokinetic and pharmacodynamic parameters of BOLD- 100 To assess potential biomarkers (GRP78) predictive of efficacy Exploratory To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours

Treatments

Therapies

Chemotherapy (NOS); Therapy (NOS)

Medications

BOLD-100 (); FOLFOX ()

Inclusion Criteria

Inclusion Criteria:

  • 18 years or older.
  • Male or non-pregnant females who agree to comply with applicable contraceptive requirements of the protocol (see Table 12. Acceptable Contraceptive Methods.)
  • Histologically and/or cytologically confirmed gastrointestinal tumours that are metastatic or unresectable, and have received at least one line of chemotherapy in the metastatic setting (in the dose escalation phase only). For the dose expansion phase, the setting will vary based on the malignancy. Colorectal cancer: Patients must have received at least 1 prior line of therapy prior to enrollment in this study. Pancreatic cancer: Patients must have received at least 1 prior line of therapy. Gastric cancer: Patients who have not received prior treatment may be included in this study. Cholangiocarcinoma: Patients must have received at least 1 prior line of therapy (with gemcitabine-based chemotherapy).
  • Have measurable disease according to RECIST v1.1 (at least one measurable lesion).
  • Have an anticipated survival of at least 16 weeks.
  • Be ambulatory, with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
  • Have adequate organ function, as defined in protocol.
  • Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion (e.g., non-steroidal anti-inflammatory drugs, corticosteroids, barbiturates, diphenylhydantoin, narcotic analgesics, probenecid). Such drugs should not be initiated while the subject is participating in this study or have been initiated within 30 days beforehand. Whenever possible, narcotic analgesic doses should be stable within 30 days prior to study entry and during the first cycle of therapy.
  • Resolved acute effects of any prior therapy to baseline severity or grade ≤1 CTCAE 5.0 except for adverse events not constituting a safety risk by investigator judgment (such as alopecia)
  • Able to take oral medications (for pre-medications and supportive management)
  • Understand and be able, willing, and likely to fully comply with study procedures and restrictions.
  • Be fully informed about their illness and the investigational nature of the study protocol, and sign a REB-approved Informed Consent Form (ICF)

  • Exclusion Criteria

    Exclusion Criteria:

  • Neuropathy > grade 2
  • Previous intolerance to or significant reaction secondary to fluorouracil or oxaliplatin
  • Cerebrovascular accident within the past 6 months.
  • History or presence of central nervous system (CNS) metastasis or leptomeningeal tumours as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.
  • Any serious medical conditions that might be aggravated by treatment or limit compliance. This includes, but is not limited to uncontrolled psychiatric disorders, serious infections, active peptic ulcer disease and bleeding diathesis
  • Any history of serious cardiac illness
  • Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months
  • Any other known malignancy within 3 years (with the exception of non-melanoma skin cancer that had undergone curative treatment, cervical cancer in situ, or ductal/lobular carcinoma in situ of the breast that has underwent local treatment
  • Active gastrointestinal tract disease with malabsorption syndrome.
  • Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.
  • Treatment with radiation therapy or surgery within one month prior to study entry.
  • Recent history of weight loss > 10% of current body weight in past 3 months.
  • Current (within 1 week of the start of the study) or regular use of any medication (including OTC, herbal or homeopathic preparations) that could affect (improve or worsen) the cancer being studied, or could affect the action or disposition of BOLD-100, or its clinical or laboratory assessment, e.g., Coumadin therapy, due to high competitive protein binding. Subjects taking ANY supplemental IRON, i.e., therapeutic or as part of a multivitamin regimen, are excluded from this study, whether prescribed or self-medicated.
  • HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.
  • Any condition potentially decreasing compliance to study procedures. Concurrent use of another investigational therapy or anti-cancer therapy.

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