Colorectal Cancer Pancreatic Cancer Gastric Cancers Cholangiocarcinoma MedDRA version: 27.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: LLT Clas
Conditions
Interventions
Product Code: BOLD-100
Pharmaceutical Form: Solution for injection/infusion
INN or Proposed INN: Not applicable (N/A)
CAS Number: 2115811-46-4
Current Sponsor code: BOLD-100
Other descriptive name: Te
Sponsors
Bold Therapeutics, Inc. (Bold)
Eligibility
Sex/Gender
All
Inclusion 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. 3. 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). 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. Colorectal cancer (ARM VII): Patients must have received only 1 prior line of therapy in the metastatic setting but remain naïve to oxaliplatin prior to enrollment in this study. 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: - 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; transaminases = 2.5 x ULN (may be up to 5 x ULN if clearly due to liver metastases), ALP = 2.5 x ULN - Renal: serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min. - Urine protein is 0, trace, or +1 on dipstick urinalysis, or =65 years) yes F.1.3.1 Number of subjects for this age range 88
Exclusion criteria
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. 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): o Previous or active myocardial infarction 470 msec 7. Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months 8. 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. 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 one month prior to study entry. 12. Recent history of weight loss > 10% of current body weight in past 3 months. 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. 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. 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. 16. Concurrent use of another investigational therapy or anti-cancer therapy. 17. Currently breastfeeding. 18. Dihydropyrimidine Dehydrogenase (DPD) deficiency. 19. Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD). 20. (ARM VII): Prior oxaliplatin treatment in the 1st line setting. 21. (ARM VII): Prior exposure to BOLD-100. 22. (ARM VII): Subjects with microsatellite-high (MSI-H) Tumours. 23. (ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF or anti-HER2).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: PART A: 1. To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours. 2. To evaluate the pharmacokinetic and pharmacodynamic parameters of BOLD-100. 3. To assess potential biomarkers (GRP78) predictive of efficacy. PART B: 1. To assess the safety, tolerability & MTD of SOC combination chemotherapy + BOLD-100 in advanced solid tumours. 2. To evaluate the pharmacokinetic and pharmacodynamic parameters of BOLD-100. 3. To assess potential biomarkers (GRP78) predictive of efficacy. ;Primary end point(s): 1. Incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0. 2. Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions. 3. Incidence of dose-limiting toxicities (DLT). 4. 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.;Timepoint(s) of evaluation of this end point: An average of 2 months for all primary end-points listed.;Main Objective: PART A (DOSE ESCALATION): To assess the safety, tolerability and Maximum Tolerated Dose (MTD) of FOLFOX standard-of-care (FOLFOX SOC) combination chemotherapy + BOLD-100 in advanced solid tumours. PART B (DOSE EXPANSION PHASE): 1. To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression Free Survival (PFS); Overall Response Rate (ORR); Overall Survival (OS). 2. Standard PK parameters including Cmin. 3. Baseline GRP78 biomarker levels (Counts/mL). 4. Changes in GRP78 biomarker levels during treatment (Counts/mL). 5. Standard PK parameters including Cmax. 6. Standard PK parameters including TSS. 7. Standard PK parameters including CSS. 8. Standard PK parameters including Vdss. ;Timepoint(s) of evaluation of this end point: An average of 2 months for all secondary end-points listed, except for the baseline GRP78 biomarker levels (this is done at baseline). | — |
Countries
Canada, Ireland, Korea, Republic of, United States
Contacts
Public ContactBold Clinical Trial Information
Bold Therapeutics, Inc. (Bold)
Outcome results
None listed