BOLD-100 + FOLFOX for Advanced Cancers
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Bold Therapeutics, Inc.
Must not be taking: Antidepressants, Coumadin, others
Disqualifiers: Neuropathy, CNS metastasis, cardiac illness, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?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.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, you should not start any new medications that affect liver or kidney function within 30 days before the trial or during the trial. It's best to discuss your current medications with the trial team to ensure they won't interfere with the study.
What makes the drug BOLD-100 unique in treating advanced cancers?
BOLD-100 combined with FOLFOX is unique because it represents a novel approach by integrating a new drug, BOLD-100, with an established chemotherapy regimen (FOLFOX), potentially offering a different mechanism of action or enhanced effectiveness compared to standard treatments for advanced cancers.
12345Eligibility Criteria
Adults with certain advanced solid tumors (pancreatic, stomach, bile duct, colorectal) who've had previous chemotherapy can join this trial. They must be expected to live at least 16 weeks, have measurable disease, good organ function and performance status. Pregnant women and those with serious medical conditions or recent surgeries are excluded.Inclusion Criteria
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
I am not pregnant and agree to follow the study's birth control requirements.
I am 18 years old or older.
+9 more
Exclusion Criteria
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
I have not had a stroke in the last 6 months.
I have or had brain metastases or tumors in the lining of my brain.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Dose Escalation
Participants receive BOLD-100 in combination with FOLFOX chemotherapy to determine tolerability and safety
8-12 weeks
Dose Expansion
Participants receive BOLD-100 in combination with FOLFOX chemotherapy to further evaluate efficacy in specific cancer types
12-24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4-8 weeks
Participant Groups
The trial is testing BOLD-100 combined with FOLFOX chemotherapy in patients with specific gastrointestinal cancers. It starts by slowly increasing the dose to find a safe level before giving it to more people to see how well it works.
11Treatment groups
Experimental Treatment
Active Control
Group I: Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI)Experimental Treatment1 Intervention
Arm closed to enrollment.
Group II: Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III)Experimental Treatment1 Intervention
Arm closed to enrollment.
Group III: Part B - Dose Expansion - 2L Gastric Cancer (ARM II)Experimental Treatment1 Intervention
Arm closed to enrollment.
Group IV: Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV)Experimental Treatment1 Intervention
Arm closed to enrollment.
Group V: Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V)Experimental Treatment1 Intervention
Arm closed to enrollment.
Group VI: Part B - Dose Expansion - 1L Gastric Cancer (ARM I)Experimental Treatment1 Intervention
Arm closed to enrollment.
Group VII: Part A - Dose Escalation - Pancreatic CancerExperimental Treatment1 Intervention
Arm closed to enrollment.
Group VIII: Part A - Dose Escalation - Gastric CancerExperimental Treatment1 Intervention
Arm closed to enrollment.
Group IX: Part A - Dose Escalation - Colorectal CancerExperimental Treatment1 Intervention
Arm closed to enrollment.
Group X: Part A - Dose Escalation - CholangiocarcinomaExperimental Treatment1 Intervention
Arm closed to enrollment.
Group XI: Part B - Dose Expansion - 2L Colorectal Cancer (ARM VII) - RandomizedActive Control1 Intervention
Arm open to enrollment.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Moffitt Cancer CenterTampa, FL
Cross Cancer InstitueEdmonton, Canada
Juravinski Cancer CentreHamilton, Canada
The Ottawa Hospital Cancer CentreOttawa, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
Bold Therapeutics, Inc.Lead Sponsor
References
FOLFIRI-bevacizumab as first-line chemotherapy in 3500 patients with advanced colorectal cancer: a pooled analysis of 29 published trials. [2022]Irinotecan and infusional bolus 5-fluorouracil (5-FU)-based chemotherapy (FOLFIRI [5-fluorouracil, folinic acid, irinotecan]) + bevacizumab (FOLFIRI-B) is 1 of the cornerstones of first-line treatment of advanced colorectal cancer (CRC). However, bevacizumab was approved for use after the AVF2107 trial that included a bolus 5-FU schedule (IFL [irinotecan + 5-FU + leucovorin]). No randomized trials have been published comparing FOLFIRI and FOLFIRI-B. The aim of this review is to pool all published data on the activity and efficacy of FOLFIRI-B as first-line therapy in treating advanced CRC in prospective and retrospective studies. We performed a systematic review, through PubMed and EMBASE, of all prospective and retrospective published studies exploring the efficacy of FOLFIRI-B as first-line chemotherapy in patients with advanced CRC. Pooled estimates of the response rate (RR) and weighted median of progression-free survival (PFS) and overall survival (OS) from all FOLFIRI-B-related studies were calculated. Rates of metastasectomy and bevacizumab-related severe toxicities were reported. A total of 29 studies (8 randomized controlled trials, 1 phase IV trial, 2 phase II trials, 4 observational studies, 4 prospective nonrandomized cohort studies, and 10 retrospective case series) were retrieved for a total of 3502 patients. Overall, the pooled RR (n = 22 publications) was 51.4%. Median PFS and OS (n = 25 and 20 publications) were 10.8 months (95% confidence interval [CI], 8.9-12.8) and 23.7 months (95% CI, 18.1-31.6), respectively. The pooled rate of surgical resection of metastases (any site of surgery: n = 7 publications) was 9.3% (range, 3.6%-24%), and rate of liver resections (liver surgery only: n = 7 publications) was 18% (range 8%-25%). Grade 3-4 bevacizumab-related toxicities were also comparable with larger phase III trials. FOLFIRI-B is used worldwide as upfront treatment for stage IV CRC. This indication is confirmed by robust data about RR, PFS, and survival obtained, which this pooled analysis of 29 trials also found. FOLFIRI-B remains 1 of the referent combinations when bevacizumab is considered as first-line therapy.
Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. [2022]Combination chemotherapy with FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) was shown to be effective in a large phase III trial.
FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies. [2022]We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged
Folfox 2 regimen in heavily pretreated patients with advanced colorectal cancer. [2022]To determine the efficacy and safety of the FOLFOX 2 regimen in patients with pretreated advanced colorectal cancer.
Management of hepatic metastases from colorectal cancer: systemic chemotherapy. [2019]The current phase III studies of chemotherapy in advanced colorectal cancer include 60% to 85% of patients with the liver as a site of metastatic disease. Within the past 10 years, various modulatory combinations of 5-fluorouracil (5-FU) with agents such as leucovorin, interferon, N-(phosphonacetyl)-L-aspartate (PALA), and methotrexate have produced higher response rates than 5-FU alone. A major seven-arm study, conducted by the Southwestern Oncology Group and reported in 1995, suggested that single-agent, continuous-infusion 5-FU demonstrated the most encouraging results. Nine of 12 reported randomized studies comparing the combination of 5-FU and leucovorin with 5-FU alone report significant increases in response rates; two studies reported significant increases in survival. The meta-analysis project involving 1381 patients confirmed the increase in response rate with the combination (23%) vs. 5-FU alone (11%) but did not demonstrate any significant difference in median survival. The current issues involving 5-FU administration largely concentrate on the best approach (modulation vs. scheduling) and comprehensive evaluation of end points (quality of life, survival, and pharmacoeconomics). The current literature examining quality-of-life issues suggests that 5-FU and low-dose leucovorin produce the best overall improvement in symptoms. Others argue that continuous-infusion scheduling is also associated with a very good quality of life (although the increased cost and morbidity of continuous-infusion administration has to be factored into this consideration). An important phase III study is currently being conducted by the National Cancer Institute of Canada comparing immediate vs. delayed (until symptomatic) chemotherapy in patients with advanced colorectal cancer. Of the new approaches to therapy, perhaps the most immediately applicable are the new thymidylate synthase inhibitors (in particular, Tomudex, which produces a response rate equivalent to that of 5-FU plus leucovorin with less toxicity and a more convenient schedule).