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

Phase 1

• Conditions: Colorectal CancerPancreatic CancerGastric CancersCholangiocarcinoma; MedDRA version: 27.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 27.0Level: LLTClassification code 10033605Term: Pancreatic cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.1Level: LLTClassification code 10017770Term: Gastric carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 27.0Level: LLTClassification code 10077846Term: Cholangiocarcinoma metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-003079-41-IE
• Lead Sponsor: Bold Therapeutics, Inc. (Bold)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-10-21
• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 220

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, 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). 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. Colorectal cancer (ARM VII): Patients must have received only 1 prior line of therapy in the metastatic setting but remain naïve to oxaliplatin prior to enrollment in this study.

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:
- Hematologic: ANC = 1.5 x 109/L, Hgb = 9.0 g/dL and platelet count = 100 x 109/L
- 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
- Renal: serum creatinine = 1.5 x ULN or creatinine clearance = 50 mL/min.
- 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. 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 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 an approved Informed Consent Form (ICF).

13. ARM VII: BRAF wild-type tumour status.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 132
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 88

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):
o Previous or active myocardial infarction < 6 months
o Congestive cardiac failure (NYHA III or IV)
o History of unstable angina pectoris < 6 months
o Recent coronary artery bypass grafting < 6 months
o Uncontrolled hypertension (systolic = 140 mmHg or diastolic = 90 mmHg)
o Ventricular arrhythmia < 6 months
o Left ventricular ejection fraction (LVEF) < 50% as measured either by radionuclide angiography or echocardiogram
o QTc interval > 470 msec

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

8. 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.

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 one month prior to study entry.

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

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. 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.

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.

16. Concurrent use of another investigational therapy or anti-cancer therapy.

17. Currently breastfeeding.

18.Dihydropyrimidine Dehydrogenase (DPD) deficiency.

19.Current or prior treatment with potent inhibitors of Dihydropyrimidine Dehydrogenase (DPD).

20.(ARM VII): Prior oxaliplatin treatment in the 1st line setting.

21.(ARM VII): Prior exposure to BOLD-100.

22.(ARM VII): Subjects with microsatellite-high (MSI-H) Tumours.

23.(ARM VII): Concurrent monoclonal antibody therapy for mCRC (anti-EGFR, anti-VEGF or anti-HER2).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified