- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04421820
BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours
September 15, 2023 updated by: Bold Therapeutics, Inc.
A Phase 1b/2a Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours
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.
Study Overview
Status
Active, not recruiting
Study Type
Interventional
Enrollment (Actual)
117
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Alberta
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Edmonton, Alberta, Canada
- Cross Cancer Institue
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Ontario
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Hamilton, Ontario, Canada
- Juravinski Cancer Centre
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Ottawa, Ontario, Canada
- The Ottawa Hospital Cancer Centre
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Toronto, Ontario, Canada
- Princess Margaret Cancer Centre
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Quebec
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Montreal, Quebec, Canada
- Jewish General Hospital
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Montréal, Quebec, Canada
- McGill University Health Centre Glen Site
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Goyang, Korea, Republic of
- National Cancer Center
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Seoul, Korea, Republic of
- Seoul National University Hospital
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Seoul, Korea, Republic of
- Samsung Medical Center
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Seoul, Korea, Republic of
- Kangbuk Samsung Hospital
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Seoul, Korea, Republic of
- Severance Hospital - Yonsei University
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California
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Santa Monica, California, United States, 90095
- University of California, Los Angeles
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Be 18 years or older.
- Be 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 are subject to receive FOLFOX as SOC per investigator's judgement. Participants will have received at least one line of chemotherapy in the metastatic setting. 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. GEJ (gastroesophageal junction) cancer patients are considered eligible to enter this trial. Cholangiocarcinoma: locally advanced or metastatic biliary tract cancer (intra or extrahepatic cholangiocarcinoma or gallbladder cancer) are eligible to enter this trial. Patients must have received at least 1 prior line of therapy (with gemcitabine-based chemotherapy). Colorectal cancer (ARM VI): Patients must have received at least 2 prior lines of therapy prior to enrollment in this study, one of which was a 5-FU based regimen.
- 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, defined as:
- Hematologic: ANC ≥ 1.5 x 109/L, Hgb ≥ 9.0 g/dL and platelet count ≥ 100 x 109/L
- Hepatic: total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for subjects with Gilbert's Syndrome); transaminases ≤ 2.5 x ULN (may be up to ≤ 5x ULN if clearly due to liver metastases) and ALP ≤ 2.5 x ULN (or ≤ 3 x ULN if liver metastases).
- Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min.
c. Urine protein is 0, trace, or +1 on dipstick urinalysis, or < 1.0 gram on 24-hour urine protein analysis
- 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 before the start of treatment. 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 before the start of treatment 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:
- Neuropathy > grade 2
- Previous intolerance to or significant reaction secondary to fluorouracil or oxaliplatin
- Cerebrovascular accident within the past 6 months before the start of treatment.
- 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 including (but not confined to):
- Previous or active myocardial infarction < 6 months before the start of treatment
- Congestive cardiac failure (NYHA III or IV)
- History of unstable angina pectoris < 6 months before the start of treatment
- Recent coronary artery bypass grafting < 6 months before the start of treatment
- Uncontrolled hypertension (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg)
- Ventricular arrhythmia < 6 months before the start of treatment
- Left ventricular ejection fraction (LVEF) < 50% as measured either by radionuclide angiography or echocardiogram
- QTc interval > 470 msec
- Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months before the start of treatment
- Any other known malignancy within 3 years before the start of treatment (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 4 weeks prior to starting treatment.
- Recent history of weight loss > 10% of current body weight in past 3 months before the start of treatment.
- 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.
- 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.
- Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part A - Dose Escalation - Gastric Cancer
Arm closed to enrollment.
|
320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks
|
Experimental: Part A - Dose Escalation - Pancreatic Cancer
Arm closed to enrollment.
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320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks
|
Experimental: Part A - Dose Escalation - Colorectal Cancer
Arm closed to enrollment.
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320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks
|
Experimental: Part A - Dose Escalation - Cholangiocarcinoma
Arm closed to enrollment.
|
320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks
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Experimental: Part B - Dose Expansion - 1L Gastric Cancer (ARM I)
Arm closed to enrollment.
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625 mg/m2 IV over 30 minutes, q2weeks
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Experimental: Part B - Dose Expansion - 2L Gastric Cancer (ARM II)
Open to enrollment.
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625 mg/m2 IV over 30 minutes, q2weeks
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Experimental: Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III)
Arm closed to enrollment.
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625 mg/m2 IV over 30 minutes, q2weeks
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Experimental: Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV)
Arm closed to enrollment.
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625 mg/m2 IV over 30 minutes, q2weeks
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Experimental: Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI)
Open to enrollment.
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625 mg/m2 IV over 30 minutes, q2weeks
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Experimental: Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V)
Arm closed to enrollment.
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625 mg/m2 IV over 30 minutes, q2weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
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Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions;
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
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Incidence of dose-limiting toxicities (DLT)
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
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Incidence of clinically significant changes or abnormalities from Physical Examinations, ECGs, Vital Signs, Laboratory Results (chemistry, hematology, coagulation, urinalysis), Eastern Cooperative Oncology Group (ECOG) performance status
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression Free Survival (PFS); Overall Response Rate (ORR); Overall Survival (OS)
Time Frame: Screening to Study Discontinuation (an average of 2 months)
|
Screening to Study Discontinuation (an average of 2 months)
|
Standard PK parameters including Cmin
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
|
Baseline GRP78 biomarker levels (Counts/mL)
Time Frame: Baseline
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Baseline
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Changes in GRP78 biomarker levels during treatment (Counts/mL)
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
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Standard PK parameters including Cmax
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
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Standard PK parameters including TSS
Time Frame: Screening to Study Discontinuation (an average of 2 months)
|
Screening to Study Discontinuation (an average of 2 months)
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Standard PK parameters including CSS
Time Frame: Screening to Study Discontinuation (an average of 2 months)
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Screening to Study Discontinuation (an average of 2 months)
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Standard PK parameters including Vdss
Time Frame: Screening to Study Discontinuation (an average of 2 months)
|
Screening to Study Discontinuation (an average of 2 months)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
August 28, 2020
Primary Completion (Estimated)
December 31, 2023
Study Completion (Estimated)
September 30, 2024
Study Registration Dates
First Submitted
May 26, 2020
First Submitted That Met QC Criteria
June 4, 2020
First Posted (Actual)
June 9, 2020
Study Record Updates
Last Update Posted (Actual)
September 18, 2023
Last Update Submitted That Met QC Criteria
September 15, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Adenocarcinoma
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Cholangiocarcinoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Protective Agents
- Micronutrients
- Vitamins
- Antidotes
- Vitamin B Complex
- Fluorouracil
- Oxaliplatin
- Leucovorin
Other Study ID Numbers
- BOLD-100-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
UNDECIDED
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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