BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours

A Phase 1b/2a Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Pancreatic Cancer; Cholangiocarcinoma; Gastric Cancers
• Intervention / Treatment: Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); Drug: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Michelle Jones; Phone Number: 604-262-9899; Email: clinical@bold-therapeutics.com
• Study Contact Backup: Name: Jim Pankovich; Phone Number: 604-262-9934; Email: jp@bold-therapeutics.com

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Recruiting
      • Cross Cancer Institue
      • Contact: Carly Mack; Phone Number: 780-432-8823; Email: Carly.Mack@ahs.ca
      • Contact: Lindzie Sinclair; Email: Lindzie.Sinclair@ahs.ca
  • Ontario
    • Hamilton, Ontario, Canada
      • Recruiting
      • Juravinski Cancer Centre
      • Contact: Carrie Ferguson; Phone Number: 64416 905-521-2100; Email: Fergusonca@hhsc.ca
      • Contact: Stephanie Skeldon; Email: Skeldon@hhsc.ca
    • Ottawa, Ontario, Canada
      • Recruiting
      • The Ottawa Hospital Cancer Centre
      • Contact: Saara Ali; Phone Number: 70211 613-737-7700; Email: saali@ohri.ca
      • Contact: Rose Leclerc; Phone Number: 70303 613-737-7700; Email: roleclerc@ohri.ca
    • Toronto, Ontario, Canada
      • Recruiting
      • Princess Margaret Cancer Centre
      • Contact: Mopina Shrikumar; Email: Mopina.Shrikumar@uhn.ca
      • Contact: Cynthia Bocaya; Phone Number: 4713 416-946-4501; Email: Cynthia.Bocaya@uhn.ca
  • Quebec
    • Montreal, Quebec, Canada
      • Recruiting
      • Jewish General Hospital
      • Contact: Yacine Tchemmoun; Email: Yacine.Tchemmoun.ccomtl@ssss.gouv.qc.ca
      • Contact: Ewa Forczek; Phone Number: 514-340-8222; Email: Ewa.Forczek.ccomtl@ssss.gouv.qc.ca
    • Montreal, Quebec, Canada
      • Recruiting
      • McGill University Health Centre Glen Site
      • Contact: Wafaa Chebaro; Email: Wafaa.Chebaro@muhc.mcgill.ca
      • Contact: Zak Dembele; Email: Aboudrazako.Dembele@muhc.mcgill.ca
• Germany
  • Bonn, Germany
    • Recruiting
    • Universitätsklinikum Bonn
    • Principal Investigator: Maria Gonzalez-Carmona
    • Contact: Maria Gonzalez-Carmona; Phone Number: +49 228 287 17014; Email: Maria.Gonzalez-Carmona@ukbonn.de
  • Ulm, Germany
    • Recruiting
    • University Hospital of Ulm
    • Principal Investigator: Thomas Seufferlein
    • Contact: Thomas Seufferlein; Phone Number: +49 731 500 44501; Email: thomas.seufferlein@uniklinik-ulm.de
• Ireland
  • Dublin, Ireland
    • Recruiting
    • St. Vincent's University Hospital
    • Contact: Fausta Barizaite; Email: fausta.barizaite@ccrt.ie
    • Contact: Fergus Keane; Email: ferguskeane@svhg.ie
    • Principal Investigator: Fergus Keane
  • Dublin, Ireland
    • Recruiting
    • St. James Hospital
    • Contact: Emily Harrold, Dr; Phone Number: +353 1 410 3000; Email: eharrold@stjames.ie
    • Principal Investigator: Emily Harrold, Dr
    • Contact: Trisha Lima; Email: TLima@stjames.ie
  • Dublin, Ireland
    • Recruiting
    • Mater Miserecordiae University Hospital
    • Principal Investigator: Austin Duffy
    • Contact: Austin Duffy; Email: austin.duffy@startdublin.com
    • Contact: Niamh Ni Obain; Email: Niamh.obain@startdublin.com
• Italy
  • Milan, Italy
    • Not yet recruiting
    • Fondazione IRCCS "Istituto Nazionale dei Tumori
    • Contact: Federica Morano; Phone Number: 390223903807; Email: Federica.Morano@istitutotumori.mi.it
    • Principal Investigator: Federica Morano
  • Naples, Italy
    • Not yet recruiting
    • AOU L. Vanvitelli
    • Contact: Stefania Napolitano; Phone Number: 393287269612; Email: stefania.napolitano@unicampania.it
    • Principal Investigator: Stefania Napolitano
  • Pisa, Italy
    • Not yet recruiting
    • Azienda Ospedaliero Universitaria Pisana
    • Principal Investigator: Chiara Cremolini
    • Contact: Chiara Cremolini; Phone Number: 39050993173; Email: chiaracremolini@gmail.com
• South Korea
  • Goyang, South Korea
    • Recruiting
    • National Cancer Center
    • Contact: Min Ji Kim; Email: 12991@ncc.re.kr
    • Contact: Yeon Hee Lee; Phone Number: 010-7109-6752; Email: Yunsoo86@ncc.re.kr
  • Seoul, South Korea
    • Recruiting
    • Samsung Medical Center
    • Contact: Yeong Seo; Phone Number: +82 2 2148 9848; Email: yeonog.seo@sbri.co.kr
  • Seoul, South Korea
    • Recruiting
    • Seoul National University Hospital
    • Contact: Hyang mi Kang; Phone Number: (+)82 2 6072 5172; Email: 49001@snuh.org
  • Seoul, South Korea
    • Recruiting
    • Kangbuk Samsung Hospital
    • Contact: Min Ju Cho; Phone Number: +82 2 2001 1526; Email: m0360.Cho@samsung.com
    • Contact: Ji Won Lee; Phone Number: +82 2 2001 1578; Email: Jiwon.Lee@samsung.com
  • Seoul, South Korea
    • Recruiting
    • Severance Hospital - Yonsei University
    • Contact: Anna Yeun; Email: annay@yuhs.ac
• Spain
  • Barcelona, Spain
    • Not yet recruiting
    • Vall Hebron Institute of Oncology (VHIO)
    • Principal Investigator: Elena Elez
    • Contact: Elena Elez; Phone Number: 34 932746000; Email: meelez@vhio.net
  • Madrid, Spain
    • Not yet recruiting
    • Hospital 12 de Octubre
    • Principal Investigator: Jorge Barriuso
    • Contact: Jorge Barriuso; Phone Number: 34 913908926; Email: jorge.barriuso.imas12@h12o.es
  • Madrid, Spain
    • Not yet recruiting
    • Early Phase Unit FJD START Madrid
    • Contact: Manuel Pedregal Trujillo; Phone Number: 34 660559027; Email: manuel.pedregal@startmadrid.com
    • Principal Investigator: Manuel Pedregal Trujillo
• United States
  • California
    • Santa Monica, California, United States, 90095
      • Completed
      • University of California, Los Angeles
  • Florida
    • Tampa, Florida, United States, 33612
      • Completed
      • Moffitt Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Be 18 years or older.
2. Be male or non-pregnant females who agree to comply with applicable contraceptive requirements of the protocol.
3. 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.
4. Have measurable disease according to RECIST v1.1.
5. Have an anticipated survival of at least 16 weeks.
6. Be ambulatory, with an ECOG performance score of 0 or 1.
7. Have adequate organ function.
8. Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion.
9. Be fully informed about their illness and the investigational nature of the study protocol, and sign a REB-approved Informed Consent Form (ICF).
10. (ARM VII): BRAF wild-type tumour status.

Exclusion Criteria:

1. Neuropathy > grade 2
2. Previous intolerance to or significant reaction secondary to fluorouracil or oxaliplatin.
3. Cerebrovascular accident within the past 6 months before the start of treatment.
4. History or presence of central nervous system (CNS) metastasis or leptomeningeal tumours.
5. Any serious medical conditions that might be aggravated by treatment or limit compliance.
6. Any history of serious cardiac illness.
7. Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months before the start of treatment.
8. Any other known malignancy within 3 years before the start of treatment.
9. Active gastrointestinal tract disease with malabsorption syndrome.
10. Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.
11. Treatment with radiation therapy or surgery within 4 weeks prior to starting treatment.
12. Recent history of weight loss > 10% of current body weight in past 3 months before the start of treatment.
13. HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.
14. Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment.
15. Currently breastfeeding
16. Dihydropyrimidine Dehydrogenase (DPD) deficiency
17. Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD)
18. (ARM VII): Prior exposure to BOLD-100
19. (ARM VII): Subjects with microsatellite-high (MSI-H) Tumours
20. (ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF or anti-HER2)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part B - Dose Expansion - 1L Gastric Cancer (ARM I); Arm closed to enrollment.	Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Experimental: Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III); Arm closed to enrollment.	Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Experimental: Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV); Arm closed to enrollment.	Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Experimental: Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V); Arm closed to enrollment.	Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Experimental: Part B - Dose Expansion - 2L Gastric Cancer (ARM II); Arm closed to enrollment.	Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Experimental: Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI); Arm closed to enrollment.	Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI); BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Active Comparator: Part B - Dose Expansion - 2L Colorectal Cancer (ARM VIIA); Arm open to enrollment. 500 mg/m2 BOLD-100 + SOC FOLFOX	Drug: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII); Arm VIIA: 500 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIB: 625 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIC: FOLFOX alone; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Active Comparator: Part B - Dose Expansion - 2L Colorectal Cancer (ARM VIIB); Arm open to enrollment. 625 mg/m2 BOLD-100 + FOLFOX	Drug: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII); Arm VIIA: 500 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIB: 625 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIC: FOLFOX alone; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.
Active Comparator: Part B - Dose Expansion - 2L Colorectal Cancer (ARM VIIC); Arm open to enrollment. FOLFOX alone.	Drug: BOLD-100 +/- FOLFOX Chemotherapy (Arm VII); Arm VIIA: 500 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIB: 625 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIC: FOLFOX alone; Other Names: BOLD-100 +/- Folinic acid (leucovorin), Fluorouracil (5-FU), and Oxaliplatin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events ([S]AEs)	Arms I-VI: Primary outcome measure; Arm VII: Secondary outcome measure	Through study completion, approximately 2 weeks after last treatment
Incidence of dose-limiting toxicities (DLT)	Dose escalation only.	Screening to 4 weeks after first treatment
Incidence of clinically significant changes or abnormalities from Physical Examinations, ECGs, Vital Signs, Laboratory Results, ECOG performance status	Arms I-VI: Primary outcome measure; Arm VII: Secondary outcome measure	Through study completion, approximately 2 weeks after last treatment
Progression Free Survival (PFS): Arm VII	Arm VII: Primary outcome measure	Through study completion, approximately 2 weeks after last treatment for last patient
Overall Response Rate (ORR): Arm VII	Arm VII: Primary outcome measure	Through study completion, approximately 2 weeks after last treatment for last patient
Overall Survival (OS): Arm VII	Arm VII: Primary outcome measure	Through study completion, approximately 2 weeks after last treatment for last patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS): Arms I-VI	Arms I-VI: Secondary outcome measure	Through study completion, approximately 2 weeks after last treatment for last patient
Overall Response Rate (ORR): Arms I-VI	Arms I-VI: Secondary outcome measure	Through study completion, approximately 2 weeks after last treatment for last patient
Overall Survival (OS): Arms I-VI	Arms I-VI: Secondary outcome measure	Through study completion, approximately 2 weeks after last treatment for last patient
Baseline and changes in biomarker levels during treatment	Serum GRP78	Arms I-VII; Through study completion, approximately 2 weeks after last treatment
Peak Plasma Concentrations (Cmax)	Arms I-VII	Arms I-VII; Through study completion, approximately 2 weeks after last treatment
Area under the plasma concentration versus time (AUC)	Arms I-VII	Arms I-VII; Through study completion, approximately 2 weeks after last treatment
Elimination half life (T1/2)	Arms I-VII	Arms I-VII; Through study completion, approximately 2 weeks after last treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of life evaluation	Arm VII	Through study completion, approximately 2 weeks after last treatment
Changes in dose reductions, treatment discontinuations, and interruptions, and AE's reported related to neuropathy from baseline	Arm VII	Through study completion, approximately 2 weeks after last treatment
Cancer mutational status in blood and tissue biomarker relationship to clinical outcomes	Circulatory tumor DNA (ctDNA) collection will be tested for a panel of tumor mutations, genomic alterations, microsatellite instability and tumor mutational burden, and these will be associated to clinical outcomes, including overall survival, progression-free survival, overall response rate and other outcome measures	Arm VII; Through study completion, approximately 2 weeks after last treatment
GRP78 levels and relationship to clinical outcomes	Optional biopsy samples at screening and at cycle 4 will be collected and analyzed for GRP78 levels, other related pathway markers, immune cell profiles, and cancer mutation profiles, and comparing these to clinical outcomes including overall survival, progression-free survival, overall response rate and other outcome measures	Arm VII; Through study completion, approximately 2 weeks after last treatment

Collaborators and Investigators

• Sponsor: Bold Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2020
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: May 26, 2020
• First Submitted That Met QC Criteria: June 4, 2020
• First Posted (Actual): June 9, 2020

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Colonic Diseases; Carcinoma; Stomach Neoplasms; Colorectal Neoplasms; Pancreatic Neoplasms; Cholangiocarcinoma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Enzymes and Coenzymes; Coordination Complexes; Pyrimidines; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Oxaliplatin; Fluorouracil; Leucovorin; KP 1339
• Other Study ID Numbers: BOLD-100-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No