BOLD-100 + FOLFOX for Advanced Cancers

Recruiting at 12 trial locations

Overseen By Michelle Jones

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bold Therapeutics, Inc.

Must not be taking: Antidepressants, Coumadin, others

Disqualifiers: Neuropathy, CNS metastasis, cardiac illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

220 Participants Needed

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. ^{1 2 3 4 5}

Eligibility 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.

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.

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

Treatment Details

Interventions

• BOLD-100

Trial Overview 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.

Participant Groups

Group I: Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI) Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group II: Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III) Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group III: Part B - Dose Expansion - 2L Gastric Cancer (ARM II) Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group IV: Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV) Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group V: Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V) Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group VI: Part B - Dose Expansion - 1L Gastric Cancer (ARM I) Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group VII: Part A - Dose Escalation - Pancreatic Cancer Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group VIII: Part A - Dose Escalation - Gastric Cancer Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group IX: Part A - Dose Escalation - Colorectal Cancer Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group X: Part A - Dose Escalation - Cholangiocarcinoma Experimental Treatment 1 Intervention

Arm closed to enrollment.

Group XI: Part B - Dose Expansion - 2L Colorectal Cancer (ARM VII) - Randomized Active Control 1 Intervention

Arm open to enrollment.

Who Is Running the Clinical Trial?

Bold Therapeutics, Inc.

Lead Sponsor

Trials

1

Recruited

220+

Findings from Research

FOLFIRI-B, a combination of irinotecan, 5-fluorouracil, and bevacizumab, shows a pooled response rate of 51.4% and median progression-free survival of 10.8 months in treating advanced colorectal cancer, based on a systematic review of 29 studies involving 3502 patients.

The treatment is associated with a surgical resection rate of 9.3% for metastases and 18% for liver resections, with severe toxicities from bevacizumab comparable to those seen in larger phase III trials, confirming its safety and efficacy as a first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFIRI-bevacizumab as first-line chemotherapy in 3500 patients with advanced colorectal cancer: a pooled analysis of 29 published trials. Petrelli, F., Borgonovo, K., Cabiddu, M., et al.[2022]

In a review of 61 patients with pancreatic adenocarcinoma treated with FOLFIRINOX, the regimen demonstrated clinical effectiveness with a median overall survival of 13.5 months, despite significant adverse events and dose modifications in over half of the treatment cycles.

The most common severe side effect was neutropenia, affecting 19.7% of patients, but there were no therapy-related deaths, indicating that while FOLFIRINOX can cause serious side effects, it remains a viable treatment option for both metastatic and locally advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. Peddi, PF., Lubner, S., McWilliams, R., et al.[2022]

In a pooled analysis of 1187 patients with early-onset metastatic colorectal cancer (EO-mCRC), the combination of FOLFOXIRI and bevacizumab demonstrated a favorable efficacy and safety profile, particularly in patients under 50 years old, who experienced fewer severe adverse events like neutropenia and asthenia compared to older patients.

Genomic profiling of EO-mCRC patients revealed specific mutations (FBXW7 and POLE) that may be characteristic of this younger demographic, suggesting potential avenues for targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies. Antoniotti, C., Germani, MM., Rossini, D., et al.[2022]

In a phase II study involving 28 patients with heavily pretreated advanced colorectal cancer, the FOLFOX 2 regimen demonstrated a partial response in 32% of patients and stable disease in 18%, with a median duration of tumor control of 24 weeks.

The treatment was found to be safe, with severe non-hematological toxicities occurring in a small percentage of patients (e.g., nausea/vomiting in 7%), and severe hematological toxicities were rare (4%), confirming the regimen's therapeutic effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Folfox 2 regimen in heavily pretreated patients with advanced colorectal cancer. Luppi, G., Zanelli, F., Di Stasi, A., et al.[2022]

Combining 5-fluorouracil (5-FU) with leucovorin has been shown to significantly increase response rates in advanced colorectal cancer patients, with a meta-analysis of 1381 patients confirming a response rate of 23% compared to 11% for 5-FU alone.

New thymidylate synthase inhibitors, like Tomudex, offer a promising alternative to traditional treatments, showing similar response rates to the 5-FU and leucovorin combination but with less toxicity and a more convenient administration schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of hepatic metastases from colorectal cancer: systemic chemotherapy. Leyland-Jones, B., Burdette-Radoux, S.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

FOLFIRI-bevacizumab as first-line chemotherapy in 3500 patients with advanced colorectal cancer: a pooled analysis of 29 published trials. [2022]

2. Italy pubmed.ncbi.nlm.nih.gov

Multi-institutional experience with FOLFIRINOX in pancreatic adenocarcinoma. [2022]

3. England pubmed.ncbi.nlm.nih.gov

FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Folfox 2 regimen in heavily pretreated patients with advanced colorectal cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Management of hepatic metastases from colorectal cancer: systemic chemotherapy. [2019]