A Phase 1b/2a Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 220
- 试验地点
- 36
- 主要终点
- Incidence and severity of adverse events ([S]AEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Have an anticipated survival of at least 16 weeks.
- •Be ambulatory, with an ECOG performance score of 0 or
- •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.
排除标准
- •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.
- •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 breastfeeding
- •Dihydropyrimidine Dehydrogenase (DPD) deficiency
- •Current 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-HER2)
研究组 & 干预措施
Part B - Dose Expansion - 2L Gastric Cancer (ARM II)
Arm closed to enrollment.
干预措施: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) (Drug)
Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI)
Arm closed to enrollment.
干预措施: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) (Drug)
Part B - Dose Expansion - 2L Colorectal Cancer (ARM VIIA)
Arm open to enrollment. 500 mg/m2 BOLD-100 + SOC FOLFOX
干预措施: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII) (Drug)
Part B - Dose Expansion - 2L Colorectal Cancer (ARM VIIB)
Arm open to enrollment. 625 mg/m2 BOLD-100 + FOLFOX
干预措施: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII) (Drug)
Part B - Dose Expansion - 2L Colorectal Cancer (ARM VIIC)
Arm open to enrollment. FOLFOX alone.
干预措施: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII) (Drug)
Part B - Dose Expansion - 1L Gastric Cancer (ARM I)
Arm closed to enrollment.
干预措施: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) (Drug)
Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III)
Arm closed to enrollment.
干预措施: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) (Drug)
Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV)
Arm closed to enrollment.
干预措施: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) (Drug)
Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V)
Arm closed to enrollment.
干预措施: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) (Drug)
结局指标
主要结局
Incidence and severity of adverse events ([S]AEs)
时间窗: 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)
时间窗: 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
时间窗: 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
时间窗: Through study completion, approximately 2 weeks after last treatment for last patient
Arm VII: Primary outcome measure
Overall Response Rate (ORR): Arm VII
时间窗: Through study completion, approximately 2 weeks after last treatment for last patient
Arm VII: Primary outcome measure
Overall Survival (OS): Arm VII
时间窗: Through study completion, approximately 2 weeks after last treatment for last patient
Arm VII: Primary outcome measure
次要结局
- Progression Free Survival (PFS): Arms I-VI(Through study completion, approximately 2 weeks after last treatment for last patient)
- Overall Response Rate (ORR): Arms I-VI(Through study completion, approximately 2 weeks after last treatment for last patient)
- Overall Survival (OS): Arms I-VI(Through study completion, approximately 2 weeks after last treatment for last patient)
- Baseline and changes in biomarker levels during treatment(Arms I-VII; Through study completion, approximately 2 weeks after last treatment)
- Peak Plasma Concentrations (Cmax)(Arms I-VII; Through study completion, approximately 2 weeks after last treatment)
- Area under the plasma concentration versus time (AUC)(Arms I-VII; Through study completion, approximately 2 weeks after last treatment)
- Elimination half life (T1/2)(Arms I-VII; Through study completion, approximately 2 weeks after last treatment)