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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04421820
Recruitment Status : Recruiting
First Posted : June 9, 2020
Last Update Posted : November 18, 2022
Sponsor:
Information provided by (Responsible Party):
Bold Therapeutics, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Colorectal Cancer Pancreatic Cancer Gastric Cancers Cholangiocarcinoma Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation) Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b/2a Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours
Actual Study Start Date : August 28, 2020
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : December 31, 2023


Arm Intervention/treatment
Experimental: Part B - Dose Expansion - 1L Gastric Cancer (ARM I) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part B - Dose Expansion - 2L Gastric Cancer (ARM II) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part B - Dose Expansion - 2L Pancreatic Cancer (ARM III) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part B - Dose Expansion - 2L Colorectal Cancer (ARM IV) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part B - Dose Expansion - 3L Colorectal Cancer (ARM VI) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part B - Dose Expansion - 2L Cholangiocarcinoma (ARM V) Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)
625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part A - Dose Escalation - Gastric Cancer
Arm closed to enrollment.
Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part A - Dose Escalation - Pancreatic Cancer
Arm closed to enrollment.
Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part A - Dose Escalation - Colorectal Cancer
Arm closed to enrollment.
Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks

Experimental: Part A - Dose Escalation - Cholangiocarcinoma
Arm closed to enrollment.
Drug: BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)
320 mg/m2 IV over 30 minutes, q2weeks; 420 mg/m2 IV over 30 minutes, q2weeks; 500 mg/m2 IV over 30 minutes, q2weeks; 625 mg/m2 IV over 30 minutes, q2weeks




Primary Outcome Measures :
  1. Incidence and severity of adverse events (AEs) according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  2. Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions; [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  3. Incidence of dose-limiting toxicities (DLT) [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  4. Incidence of clinically significant changes or abnormalities from Physical Examinations, ECGs, Vital Signs, Laboratory Results (chemistry, hematology, coagulation, urinalysis), Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]

Secondary Outcome Measures :
  1. Progression Free Survival (PFS); Overall Response Rate (ORR); Overall Survival (OS) [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  2. Standard PK parameters including Cmin [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  3. Baseline GRP78 biomarker levels (Counts/mL) [ Time Frame: Baseline ]
  4. Changes in GRP78 biomarker levels during treatment (Counts/mL) [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  5. Standard PK parameters including Cmax [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  6. Standard PK parameters including TSS [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  7. Standard PK parameters including CSS [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]
  8. Standard PK parameters including Vdss [ Time Frame: Screening to Study Discontinuation (an average of 2 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 (see Table 12. Acceptable Contraceptive Methods.)
  3. 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.
  4. Have measurable disease according to RECIST v1.1 (at least one measurable lesion).
  5. Have an anticipated survival of at least 16 weeks.
  6. Be ambulatory, with an Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1.
  7. Have adequate organ function, defined as:

    1. Hematologic: ANC ≥ 1.5 x 109/L, Hgb ≥ 9.0 g/dL and platelet count ≥ 100 x 109/L
    2. Hepatic: total bilirubin ≤ 1.5 x ULN (or ≤ 3 x ULN for subjects with Gilbert's Syndrome); transaminases ≤ 2.5 x ULN (may be up to ≤ 5x ULN if clearly due to liver metastases) and ALP ≤ 2.5 x ULN (or ≤ 3 x ULN if liver metastases).
    3. Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min.

    c. Urine protein is 0, trace, or +1 on dipstick urinalysis, or < 1.0 gram on 24-hour urine protein analysis

  8. Be on stable doses of any drugs that may affect hepatic drug metabolism or renal drug excretion (e.g., non-steroidal anti-inflammatory drugs, corticosteroids, barbiturates, diphenylhydantoin, narcotic analgesics, probenecid). Such drugs should not be initiated while the subject is participating in this study or have been initiated within 30 days beforehand before the start of treatment. Whenever possible, narcotic analgesic doses should be stable within 30 days prior to study entry and during the first cycle of therapy.
  9. Resolved acute effects of any prior therapy before the start of treatment to baseline severity or grade ≤1 CTCAE 5.0 except for adverse events not constituting a safety risk by investigator judgment (such as alopecia)
  10. Able to take oral medications (for pre-medications and supportive management)
  11. Understand and be able, willing, and likely to fully comply with study procedures and restrictions.
  12. Be fully informed about their illness and the investigational nature of the study protocol, and sign a REB-approved Informed Consent Form (ICF).

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 as documented by CT or MRI scan, analysis of cerebrospinal fluid or neurological exam.
  5. Any serious medical conditions that might be aggravated by treatment or limit compliance. This includes, but is not limited to uncontrolled psychiatric disorders, serious infections, active peptic ulcer disease and bleeding diathesis
  6. 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
  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 (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
  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. 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.
  14. HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.
  15. Any condition potentially decreasing compliance to study procedures. Concurrent use of another investigational therapy or anti-cancer therapy.
  16. Concurrent use of another investigational therapy or anti-cancer therapy within 4 weeks before the start of treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04421820


Contacts
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Contact: Michelle Jones 604-262-9899 clinical@bold-therapeutics.com
Contact: Jim Pankovich 604-262-9934 jp@bold-therapeutics.com

Locations
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United States, California
University of California, Los Angeles Recruiting
Santa Monica, California, United States, 90095
Contact: Rachel Andes    310-633-8400    RAndes@mednet.ucla.edu   
Contact: Bindu Cherian       BCherian@mednet.ucla.edu   
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
Contact: Lauren Ponto    813-745-7658    Lauren.Ponto@moffitt.org   
Canada, Alberta
Cross Cancer Institue Recruiting
Edmonton, Alberta, Canada
Contact: Carly Mack    780-432-8823    Carly.Mack@ahs.ca   
Contact: Lindzie Sinclair       Lindzie.Sinclair@ahs.ca   
Canada, Ontario
Juravinski Cancer Centre Recruiting
Hamilton, Ontario, Canada
Contact: Carrie Ferguson    905-521-2100 ext 64416    Fergusonca@hhsc.ca   
Contact: Stephanie Skeldon       Skeldon@hhsc.ca   
The Ottawa Hospital Cancer Centre Recruiting
Ottawa, Ontario, Canada
Contact: Saara Ali    613-737-7700 ext 70211    saali@ohri.ca   
Contact: Rose Leclerc    613-737-7700 ext 70303    roleclerc@ohri.ca   
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada
Contact: Mopina Shrikumar       Mopina.Shrikumar@uhn.ca   
Contact: Cynthia Bocaya    416-946-4501 ext 4713    Cynthia.Bocaya@uhn.ca   
Canada, Quebec
Jewish General Hospital Recruiting
Montreal, Quebec, Canada
Contact: Yacine Tchemmoun       Yacine.Tchemmoun.ccomtl@ssss.gouv.qc.ca   
Contact: Ewa Forczek    514-340-8222    Ewa.Forczek.ccomtl@ssss.gouv.qc.ca   
McGill University Health Centre Glen Site Recruiting
Montréal, Quebec, Canada
Contact: Wafaa Chebaro       Wafaa.Chebaro@muhc.mcgill.ca   
Contact: Zak Dembele       Aboudrazako.Dembele@muhc.mcgill.ca   
Korea, Republic of
National Cancer Center Recruiting
Goyang, Korea, Republic of
Contact: Min Ji Kim       12991@ncc.re.kr   
Contact: Yeon Hee Lee    010-7109-6752    Yunsoo86@ncc.re.kr   
Kangbuk Samsung Hospital Recruiting
Seoul, Korea, Republic of
Contact: Min Ju Cho    +82 2 2001 1526    m0360.Cho@samsung.com   
Contact: Ji Won Lee    +82 2 2001 1578    Jiwon.Lee@samsung.com   
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Yeong Seo    +82 2 2148 9848    yeonog.seo@sbri.co.kr   
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Hyang mi Kang    (+)82 2 6072 5172    49001@snuh.org   
Severance Hospital - Yonsei University Recruiting
Seoul, Korea, Republic of
Contact: Anna Yeun       annay@yuhs.ac   
Sponsors and Collaborators
Bold Therapeutics, Inc.
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Responsible Party: Bold Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04421820    
Other Study ID Numbers: BOLD-100-001
First Posted: June 9, 2020    Key Record Dates
Last Update Posted: November 18, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cholangiocarcinoma
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Leucovorin
Fluorouracil
Oxaliplatin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antidotes
Protective Agents
Vitamin B Complex
Vitamins
Micronutrients