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

• Sponsor: Bold Therapeutics, Inc. (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04421820
• Collaborator: (none)
• Enrollment: 80
• Locations: 13
• Arms: 4
• Anticipated Duration (Months): 28.1
• Patients Per Site: 6.2
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Dose Escalation Study of BOLD-100 in Combination With FOLFOX Chemotherapy in Patients With Advanced Solid Tumours
• Actual Study Start Date: Aug 28, 2020
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Gastric Cancer	Drug: BOLD-100 in combination with FOLFOX Chemotherapy; 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: Pancreatic Cancer	Drug: BOLD-100 in combination with FOLFOX Chemotherapy; 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: Colorectal Cancer	Drug: BOLD-100 in combination with FOLFOX Chemotherapy; 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: Cholangiocarcinoma	Drug: BOLD-100 in combination with FOLFOX Chemotherapy; 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

Outcome Measures

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 [Screening to Study Discontinuation (an average of 2 months)]

2. Incidence of serious adverse events (SAE) and suspected unexpected serious adverse reactions; [Screening to Study Discontinuation (an average of 2 months)]

3. Incidence of dose-limiting toxicities (DLT) [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 [Screening to Study Discontinuation (an average of 2 months)]

Secondary Outcome Measures

1. Progression Free Survival (PFS); Overall Response Rate (ORR); Overall Survival (OS) [Screening to Study Discontinuation (an average of 2 months)]

2. Standard PK parameters including Cmin [Screening to Study Discontinuation (an average of 2 months)]

3. Baseline GRP78 biomarker levels (Counts/mL) [Baseline]

4. Changes in GRP78 biomarker levels during treatment (Counts/mL) [Screening to Study Discontinuation (an average of 2 months)]

5. Standard PK parameters including Cmax [Screening to Study Discontinuation (an average of 2 months)]

6. Standard PK parameters including TSS [Screening to Study Discontinuation (an average of 2 months)]

7. Standard PK parameters including CSS [Screening to Study Discontinuation (an average of 2 months)]

8. Standard PK parameters including Vdss [Screening to Study Discontinuation (an average of 2 months)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 have received at least one line of chemotherapy in the metastatic setting (in the dose escalation phase only). For the dose expansion phase, the setting will vary based on the malignancy. 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. Cholangiocarcinoma: Patients must have received at least 1 prior line of therapy (with gemcitabine-based chemotherapy).

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:

8. Hematologic: ANC ≥ 1.5 x 109/L, Hgb ≥ 9.0 g/dL and platelet count ≥ 100 x 109/L

9. Hepatic: total bilirubin ≤ 1.5 x ULN; transaminases ≤ 2.5 x ULN (may be up to 5 x ULN if clearly due to liver metastases), ALP ≤ 2.5 x ULN

10. Renal: serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min.

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

1. 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. Whenever possible, narcotic analgesic doses should be stable within 30 days prior to study entry and during the first cycle of therapy.

2. Resolved acute effects of any prior therapy to baseline severity or grade ≤1 CTCAE 5.0 except for adverse events not constituting a safety risk by investigator judgment (such as alopecia)

3. Able to take oral medications (for pre-medications and supportive management)

4. Understand and be able, willing, and likely to fully comply with study procedures and restrictions.

5. 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.

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

• Congestive cardiac failure (NYHA III or IV)

• History of unstable angina pectoris < 6 months

• Recent coronary artery bypass grafting < 6 months

• Uncontrolled hypertension (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg)

• Ventricular arrhythmia < 6 months

• Left ventricular ejection fraction (LVEF) < 50% as measured either by radionuclide angiography or echocardiogram

• QTc interval > 470 msec

1. Hemoptysis, cerebral, or clinically significant gastrointestinal hemorrhage in the past 6 months

2. Any other known malignancy within 3 years (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

3. Active gastrointestinal tract disease with malabsorption syndrome.

4. Non-healing wound, fracture, or ulcer, or presence of symptomatic peripheral vascular disease.

5. Treatment with radiation therapy or surgery within one month prior to study entry.

6. Recent history of weight loss > 10% of current body weight in past 3 months.

7. 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. Subjects taking ANY supplemental IRON, i.e., therapeutic or as part of a multivitamin regimen, are excluded from this study, whether prescribed or self-medicated.

8. HIV-positive subjects on combination anti-retroviral therapy due to the potential for PK interactions with the study agent.

9. Any condition potentially decreasing compliance to study procedures. Concurrent use of another investigational therapy or anti-cancer therapy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Santa Monica	California	United States	90095
2	Moffitt Cancer Center	Tampa	Florida	United States	33612
3	Cross Cancer Institue	Edmonton	Alberta	Canada
4	Juravinski Cancer Centre	Hamilton	Ontario	Canada
5	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada
6	Princess Margaret Cancer Centre	Toronto	Ontario	Canada
7	Jewish General Hospital	Montreal	Quebec	Canada
8	McGill University Health Centre Glen Site	Montréal	Quebec	Canada
9	National Cancer Center	Goyang		Korea, Republic of
10	Kangbuk Samsung Hospital	Seoul		Korea, Republic of
11	Samsung Medical Center	Seoul		Korea, Republic of
12	Seoul National University Hospital	Seoul		Korea, Republic of
13	Severance Hospital - Yonsei University	Seoul		Korea, Republic of

Sponsors and Collaborators

• Bold Therapeutics, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bold Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT04421820
• Other Study ID Numbers: BOLD-100-001
• First Posted: Jun 9, 2020
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Cholangiocarcinoma

Study Results

No Results Posted as of Aug 19, 2022