A Phase Ib/IIa Dose Escalation Study of BOLD-100 in Combination with FOLFOX Chemotherapy in Patients with Advanced Solid Tumours
Study Identifier:
BOLD-100-001
CT.gov Identifier:
EudraCT Identifier:
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Recruiting
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Study Summary
To Evaluate the safety and preliminary efficacy of BOLD-100 in combination with FOLFOX for the treatment of gastric, pancreatic, colorectal and bile duct cancers. In the dose-escalation phase (Part A), patients will be enrolled to determine the combination recommended dose using a standard 3+3 design. 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 tumors. PART B (DOSE EXPANSION PHASE): 1. To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumors The primary objective of Part B is to evaluate the efficacy of BOLD-100 in three clinical endpoints (PFS, OS, and ORR). Bayesian modelling is used to continually reassess these endpoints; the posterior probability of superiority to a historical landmark for each endpoint. Disease Control Rates (DCR) for each cohort are also determined. Bayesian modelling is used to continually reassess these endpoints, the posterior probability of superiority to an historical landmark for each endpoint. This study explored the benefit of BOLD-100 + FOLFOX in previously treated mCRC patients. To evaluate BOLD-100 + FOLFOX in pts with mCRC. To evaluates BOLD-100 + FOLFOX in pts with metastatic colorectal cancer (mCRC)
Primary objectives are to evaluate progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) by RECIST v1.1.
To further demonstrate BOLD-100's potential as a transformative therapy in early-line colorectal cancer, biliary tract cancer and other solid tumour indications.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
N/A
Age
18 - 100 Years
Study Drug
Study Status
Indicates the current recruitment status or the expanded access status
Recruiting
Requirements information
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. 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.
- 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).
- (ARM VII): BRAF wild-type tumour status
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.
- Currently breastfeeding
- Dihydropyrimidine Dehydrogenase (DPD) deficiency
- Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD)
- (ARM VII): Prior oxaliplatin treatment in the 1st line setting
- (ARM VII): Prior exposure to BOLD-100
- (ARM VII): Subjects with microsatellite-high (MSI-H) Tumours
- (ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF or anti-HER2)
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Dublin
Dublin, Ireland, D07 R2WY
Investigator
Austin Duffy
Status
Recruiting
Condition(s) Treated at Site
Bowel (Colorectal)
Pancreas
Gastric
Bile Duct