Brief Title
BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours
Official Title
A Phase 1b/2a Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours
Brief 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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0
Secondary Outcome
Progression Free Survival (PFS); Overall Response Rate (ORR); Overall Survival (OS)
Condition
Colorectal Cancer
Intervention
BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
Study Arms / Comparison Groups
Part B - Dose Expansion - 1L Gastric Cancer (ARM I)
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
August 28, 2020
Completion Date
September 30, 2024
Primary Completion Date
December 31, 2023
Eligibility Criteria
Inclusion Criteria:
1. Be 18 years or older.
2. Be male or non-pregnant females who agree to comply with applicable contraceptive
requirements of the protocol (see Table 12. Acceptable Contraceptive Methods.)
3. 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.
4. Have measurable disease according to RECIST v1.1 (at least one measurable lesion).
5. Have an anticipated survival of at least 16 weeks.
6. Be ambulatory, with an Eastern Cooperative Oncology Group (ECOG) performance score of
0 or 1.
7. Have adequate organ function, defined as:
1. Hematologic: ANC ≥ 1.5 x 109/L, Hgb ≥ 9.0 g/dL and platelet count ≥ 100 x 109/L
2. 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).
3. 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
8. 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.
9. 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)
10. Able to take oral medications (for pre-medications and supportive management)
11. Understand and be able, willing, and likely to fully comply with study procedures and
restrictions.
12. 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:
1. Neuropathy > grade 2
2. Previous intolerance to or significant reaction secondary to fluorouracil or
oxaliplatin
3. Cerebrovascular accident within the past 6 months before the start of treatment.
4. 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.
5. 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
6. 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
7. Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the
past 6 months before the start of treatment
8. 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
9. Active gastrointestinal tract disease with malabsorption syndrome.
10. Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular
disease.
11. Treatment with radiation therapy or surgery within 4 weeks prior to starting
treatment.
12. Recent history of weight loss > 10% of current body weight in past 3 months before the
start of treatment.
13. 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.
14. HIV-positive subjects on combination anti-retroviral therapy due to the potential for
PK interactions with the study agent.
15. Any condition potentially decreasing compliance to study procedures. Concurrent use of
another investigational therapy or anti-cancer therapy.
16. Concurrent use of another investigational therapy or anti-cancer therapy within 4
weeks before the start of treatment.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
, 604-262-9899, [email protected]
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT04421820
Organization ID
BOLD-100-001
Responsible Party
Sponsor
Study Sponsor
Bold Therapeutics, Inc.
Study Sponsor
, ,
Verification Date
February 2023