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:
NCT04421820
EudraCT Identifier:
202200000000
EU Trial (CTIS) Number:
2024-517500-11-00
Study Contact Information:
(210) 593-5651 or [email protected]
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.

Main objective (English)

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): To assess response rates to SOC combination chemotherapy + BOLD-100 in advanced solid tumours.

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.
Bowel (Colorectal)
Pancreas
Gastric
Bile Duct
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.
Phase I/II
Sex
N/A
Age
18 - 100 Years
Study Drug
Drug: Experimental: Part B - Dose Expansion - 1L Gastric Cancer (ARM I)
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.
  • 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.
  • Have measurable disease according to RECIST v1.1.
  • Have an anticipated survival of at least 16 weeks.
  • Be ambulatory, with an ECOG performance score of 0 or 1.
  • Have adequate organ function.
  • Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion.
  • 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.
  • As per CTIS:
  • Be 18 years or older.
  • 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 an approved Informed Consent Form (ICF).
  • Be male or non-pregnant females who agree to comply with applicable contraceptive requirements of the protocol.
  • Histologically and/or cytologically confirmed gastrointestinal tumours that are metastatic or unresectable, and are subject to receive FOLFOX as standard of care per investigator judgement. Participants will 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 prior to erollment in this study. Prior oxaliplatin therapy is permitted in the following two situations: 1. patients who have received oxaliplatin in the adjuvant setting. 2. patients who have received oxaliplatin in the first line metastatic setting but did not progress on treatment or within 3 months of oxaliplatin treatment cessation.
  • 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; 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 < 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 may be initiated while the subject is participating in this study.
  • Resolved acute effects of any prior therapy to baseline severity or grade ≤1 CTCAE 5.0 except for adverse events not constituting a safety risk by investigator judgment (such as alopecia)\
  • (ARM VII): BRAF wild-type tumour status.
Exclusion criteria
  • Neuropathy > grade 2Previous 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.Any serious medical conditions that might be aggravated by treatment or limit compliance.Any history of serious cardiac illness.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.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.HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment.Currently breastfeedingDihydropyrimidine Dehydrogenase (DPD) deficiencyCurrent or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD)(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-HER2As per CTIS:
  • Neuropathy > grade 2
  • Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.
  • Treatment with radiation therapy or surgery within 1 month prior to study entry.
  • Recent history of weight loss > 10% of current body weight in past 3 months.
  • 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.
  • 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.
  • Previous intolerance to or significant reaction secondary to fluorouracil or oxaliplatin
  • (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)
  • Cerebrovascular accident within the past 6 months.
  • 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): o Previous or active myocardial infarction < 6 months o Congestive cardiac failure (NYHA III or IV) o History of unstable angina pectoris < 6 months o Recent coronary artery bypass grafting < 6 months o Uncontrolled hypertension (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) o Ventricular arrhythmia < 6 months o Left ventricular ejection fraction (LVEF) < 50% as measured either by radionuclide angiography or echocardiogram o QTc interval > 470 msec
  • Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months.
  • 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.
  • (ARM VII): Patients considered resitant to Oxaliplatin: Patients who have received oxaliplatin in the adjuvat setting who have progressed / relapsed within 6 months of their last oxaliplatin administration. Patients with advanced colorectal cancer who have progressed (based on RECIST 1.1) while on or within 3 months of their last administration of oxaliplatin.
  • Currently breastfeeding
  • Dihydropyrimidine Dehydrogenase (DPD) deficiency (Note: when tested/required prior to administration of 5-fluorouracil (5-FU) as per Principal Investigator’s best medical judgement and based on the local practice guidelines and 5-FU local prescribing instructions. In the EU, DPD testing is required, while in other countries it may be recommended).
  • Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD).

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