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.
BOLD-100 is a novel, targeted anti-cancer therapy which is an intravenously administered small molecule drug. In a previous Phase 1 study (NCT01415297) BOLD-100 showed low toxicity with minimal hematological issues as well as some potential anti-tumour activity. The lack of observed hematological toxicity and neurotoxicity position BOLD-100 well for use in combination with a broad range of standard-of-care (SOC) chemotherapy regimens. This is a prospective, multicenter non-randomized Phase 1b/2a dose escalation \& expanded cohort study of BOLD-100 in patients with advanced gastrointestinal malignancies (colorectal, pancreatic, gastric cancers, and cholangiocarcinoma) receiving standard-of-care FOLFOX chemotherapy. Enrollment in Arms I - VI is closed to enrollment. Colorectal cancer (ARM VII) for patients who are oxaliplatin naïve and have received only 1 prior line of therapy in the metastatic setting. Within this arm, participants will be randomized to one of two dose levels of BOLD-100 - either 500 mg/m2 or 625 mg/m2 in combination with FOLFOX or FOLFOX alone, in a 1:1:1 ratio. Participants enrolled into Arm VII will complete quality of life questionnaires examining general quality of life and neuropathy associated quality of life parameters.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Arm VIIA: 500 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIB: 625 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIC: FOLFOX alone
BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy
University of California, Los Angeles
Santa Monica, California, United States
COMPLETEDMoffitt Cancer Center
Tampa, Florida, United States
COMPLETEDCross Cancer Institue
Edmonton, Alberta, Canada
RECRUITINGJuravinski Cancer Centre
Hamilton, Ontario, Canada
RECRUITINGThe Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada
RECRUITINGPrincess Margaret Cancer Centre
Toronto, Ontario, Canada
RECRUITINGJewish General Hospital
Montreal, Quebec, Canada
RECRUITINGMcGill University Health Centre Glen Site
Montreal, Quebec, Canada
RECRUITINGMater Miserecordiae University Hospital
Dublin, Ireland
RECRUITINGSt. James Hospital
Dublin, Ireland
RECRUITING...and 6 more locations
Incidence and severity of adverse events ([S]AEs)
Arms I-VI: Primary outcome measure; Arm VII: Secondary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment
Incidence of dose-limiting toxicities (DLT)
Dose escalation only.
Time frame: Screening to 4 weeks after first treatment
Incidence of clinically significant changes or abnormalities from Physical Examinations, ECGs, Vital Signs, Laboratory Results, ECOG performance status
Arms I-VI: Primary outcome measure; Arm VII: Secondary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment
Progression Free Survival (PFS): Arm VII
Arm VII: Primary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment for last patient
Overall Response Rate (ORR): Arm VII
Arm VII: Primary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment for last patient
Overall Survival (OS): Arm VII
Arm VII: Primary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment for last patient
Progression Free Survival (PFS): Arms I-VI
Arms I-VI: Secondary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment for last patient
Overall Response Rate (ORR): Arms I-VI
Arms I-VI: Secondary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment for last patient
Overall Survival (OS): Arms I-VI
Arms I-VI: Secondary outcome measure
Time frame: Through study completion, approximately 2 weeks after last treatment for last patient
Baseline and changes in biomarker levels during treatment
Serum GRP78
Time frame: Arms I-VII; Through study completion, approximately 2 weeks after last treatment
Peak Plasma Concentrations (Cmax)
Arms I-VII
Time frame: Arms I-VII; Through study completion, approximately 2 weeks after last treatment
Area under the plasma concentration versus time (AUC)
Arms I-VII
Time frame: Arms I-VII; Through study completion, approximately 2 weeks after last treatment
Elimination half life (T1/2)
Arms I-VII
Time frame: Arms I-VII; Through study completion, approximately 2 weeks after last treatment
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