BOLD-100 + FOLFOX for Advanced Cancers

Recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called BOLD-100, administered with standard chemotherapy (FOLFOX), to determine its effectiveness in treating certain advanced cancers. The focus is on colorectal and gastric cancers that have spread or cannot be surgically removed. The study aims to identify the optimal dose and assess the safety and effectiveness of this combination. Individuals with these cancer types who have already received some treatment but require further intervention might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that BOLD-100, when combined with FOLFOX chemotherapy, is generally well-tolerated by patients. Studies have found this combination effective for individuals with advanced stomach and colon cancers. Importantly, these studies have identified no new safety issues, indicating that BOLD-100 with FOLFOX is safe for those who have undergone extensive cancer treatments. The treatment has undergone multiple testing stages, further supporting its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

BOLD-100 is unique because it targets the stress response pathways in cancer cells, which can make these cells more vulnerable to existing chemotherapy treatments like FOLFOX. Unlike traditional chemotherapy that directly attacks cancer cells, BOLD-100 enhances the effectiveness of these treatments by disrupting cancer cell defenses. Additionally, BOLD-100 is being explored for its potential to work across multiple cancer types, offering a versatile option in cancer treatment. Researchers are excited about its promise to improve outcomes for patients with advanced cancers, especially where standard treatments may have limited success.

What evidence suggests that BOLD-100 combined with FOLFOX could be effective for advanced cancers?

This trial examines BOLD-100 for its potential in treating various advanced cancers. Previous studies have shown promising results for BOLD-100 in advanced stomach cancer, where patients lived longer without disease progression. For colon cancer, early results indicated positive effects on both safety and effectiveness, with the treatment being well-tolerated and having strong impacts in advanced cases. Additionally, BOLD-100 stopped pancreatic cancer cells from growing and caused them to die. In bile duct cancer, BOLD-100 combined with FOLFOX helped patients live longer and delayed disease progression. Overall, these findings suggest that BOLD-100 could be an effective treatment option for various advanced cancers. Participants in this trial may receive BOLD-100 in different treatment arms, including combinations with FOLFOX, to further evaluate its effectiveness across different cancer types. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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.

Have an anticipated survival of at least 16 weeks

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

Citations

1. ccanewsonline.com ccanewsonline.com/issues/2024/september-2024-vol-5-no-3/3108:the-use-of-bold-100-alongside-folfox-has-the-potential

The Use of BOLD-100 Alongside FOLFOX Has ... The combination of BOLD-100 and FOLFOX has proven to be an effective and well-tolerated treatment regimen for pretreated, advanced metastatic BTC.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4098

BOLD-100-001 (TRIO039): A phase 1b/2a study of ... BOLD-100 plus FOLFOX is an active and well-tolerated treatment regimen in the heavily pre-treated Stage IV biliary tract and gastric cancer study populations.

3. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/LB432/761500/Abstract-LB432-Clinical-stage-anticancer-agent

Abstract LB432: Clinical-stage anticancer agent BOLD-100 ... Clinical results have shown that BOLD-100 combined with FOLFOX improves overall survival (OS) and progression-free survival (PFS) in patients ...

4. biospace.com biospace.com/bold-therapeutics-presents-jaw-dropping-interim-phase-2-clinical-data-for-bold-100-in-the-treatment-of-advanced-colorectal-cancer-at-aacr-2023

Bold Therapeutics Presents Jaw-Dropping Interim Phase 2 ... These results clearly demonstrate that BOLD-100 has the potential to significantly improve treatment outcomes in both solid and liquid tumors, ...

5. pharmaceutical-technology.com pharmaceutical-technology.com/data-insights/bold-100-bold-therapeutics-bile-duct-cancer-cholangiocarcinoma-likelihood-of-approval/?utm_source=lgp5-loa&utm_medium=24-223399&utm_campaign=recommended-articles

BOLD-100 by Bold Therapeutics for Bile Duct Cancer ... BOLD-100 is under clinical development by Bold Therapeutics and currently in Phase II for Bile Duct Cancer (Cholangiocarcinoma).

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4059

A phase 2 study of BOLD-100 in combination with FOLFOX ... BOLD-100 plus FOLFOX is an active, well-tolerated treatment regimen in the heavily pre-treated advanced GC.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4115

A phase 2 study of BOLD-100 in combination with FOLFOX ... BOLD-100 combined with FOLFOX is an active and well-tolerated treatment regimen in Stage IV BTC. There were no new safety signals detected.

8. bold-therapeutics.com bold-therapeutics.com/news-post?id=2076fd3d-3ae0-4269-ae13-d27657ac482e

News Post Bold Therapeutics Announces Positive Phase 2 Safety and Efficacy Results for BOLD-100 in Advanced Metastatic Colorectal Cancer at ASCO GI 2024.

9. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT149/725188/Abstract-CT149-BOLD-100-001-TRIO039-a-phase-1b-2a

Abstract CT149: BOLD-100-001 (TRIO039): a phase 1b/2a ... BOLD-100 plus FOLFOX is an active and well-tolerated treatment regimen in the heavily pre-treated metastatic CRC trial population.

10. bold-therapeutics.com bold-therapeutics.com/technology

Bold Therapeutics | Technology The BOLD-100 development program builds on the Phase 2 efficacy and safety data indicating multiple opportunities for further randomized clinical trials.