Cholangiocarcinoma, Colorectal Cancer, Gastric Cancers, Pancreatic Cancer
Conditions
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.
Detailed description
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.
Interventions
DRUGBOLD-100 +/- FOLFOX Chemotherapy (Arm VII)
Arm VIIA: 500 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIB: 625 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIC: FOLFOX alone
DRUGBOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI)
BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy
Sponsors
Bold Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized - Arm VII only: Second line mCRC 500 mg/m2 or 625 mg/m2 in combination with FOLFOX or FOLFOX alone, in a 1:1:1 ratio.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. 3. Histologically and/or cytologically confirmed gastrointestinal tumours that are metastatic or unresectable. (ARM VII): Patients must have received only 1 prior line of therapy in the metastatic setting. 4. Have measurable disease according to RECIST v1.1. 5. Have an anticipated survival of at least 16 weeks. 6. Be ambulatory, with an ECOG performance score of 0 or 1. 7. Have adequate organ function. 8. Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion. 9. Be fully informed about their illness and the investigational nature of the study protocol, and sign a REB-approved Informed Consent Form (ICF). 10. (ARM VII): BRAF wild-type tumour status.
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. 5. Any serious medical conditions that might be aggravated by treatment or limit compliance. 6. Any history of serious cardiac illness. 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. 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. HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent. 14. Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment. 15. Currently breastfeeding 16. Dihydropyrimidine Dehydrogenase (DPD) deficiency 17. Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD) 18. (ARM VII): Prior exposure to BOLD-100 19. (ARM VII): Subjects with microsatellite-high (MSI-H) Tumours 20. (ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF or anti-HER2)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and severity of adverse events ([S]AEs) | Through study completion, approximately 2 weeks after last treatment | Arms I-VI: Primary outcome measure; Arm VII: Secondary outcome measure |
| Incidence of dose-limiting toxicities (DLT) | Screening to 4 weeks after first treatment | Dose escalation only. |
| Incidence of clinically significant changes or abnormalities from Physical Examinations, ECGs, Vital Signs, Laboratory Results, ECOG performance status | Through study completion, approximately 2 weeks after last treatment | Arms I-VI: Primary outcome measure; Arm VII: Secondary outcome measure |
| Progression Free Survival (PFS): Arm VII | Through study completion, approximately 2 weeks after last treatment for last patient | Arm VII: Primary outcome measure |
| Overall Response Rate (ORR): Arm VII | Through study completion, approximately 2 weeks after last treatment for last patient | Arm VII: Primary outcome measure |
| Overall Survival (OS): Arm VII | Through study completion, approximately 2 weeks after last treatment for last patient | Arm VII: Primary outcome measure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS): Arms I-VI | Through study completion, approximately 2 weeks after last treatment for last patient | Arms I-VI: Secondary outcome measure |
| Overall Response Rate (ORR): Arms I-VI | Through study completion, approximately 2 weeks after last treatment for last patient | Arms I-VI: Secondary outcome measure |
| Overall Survival (OS): Arms I-VI | Through study completion, approximately 2 weeks after last treatment for last patient | Arms I-VI: Secondary outcome measure |
| Baseline and changes in biomarker levels during treatment | Arms I-VII; Through study completion, approximately 2 weeks after last treatment | Serum GRP78 |
| Peak Plasma Concentrations (Cmax) | Arms I-VII; Through study completion, approximately 2 weeks after last treatment | Arms I-VII |
| Area under the plasma concentration versus time (AUC) | Arms I-VII; Through study completion, approximately 2 weeks after last treatment | Arms I-VII |
| Elimination half life (T1/2) | Arms I-VII; Through study completion, approximately 2 weeks after last treatment | Arms I-VII |
Countries
Canada, Germany, Ireland, Italy, South Korea, Spain, United States
Contacts
CONTACTMichelle Jones
CONTACTJim Pankovich
Outcome results
None listed