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NCT04421820 | RECRUITING | Colorectal Cancer

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

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

Colorectal Cancer

Pancreatic Cancer

Gastric Cancers

Cholangiocarcinoma

Intervention/treatment

BOLD-100 in combination with FOLFOX Chemotherapy (Dose Expansion)

BOLD-100 in combination with FOLFOX Chemotherapy (Dose Escalation)

Phase

PHASE1

PHASE2

Study Type : INTERVENTIONAL
Estimated Enrollment : 220 participants
Masking : NONE
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 : 2020-08-28
Estimated Primary Completion Date : 2026-06-01
Estimated Study Completion Date : 2026-09-01

Information not available for Arms and Intervention/treatment

Ages Eligible for Study: 18 Years
Sexes Eligible for Study: ALL
Accepts Healthy Volunteers:
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. 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
    • 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).
    • 13. (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 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.
      • 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)
BOLD-100 in Combination With FOLFOX for the Treatment of Advanced Solid Tumours

Location Details

NCT04421820

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How to Participate

Want to participate in this study, select a site at your convenience, send yourself email to get contact details and prescreening steps.

Locations

RECRUITING

United States, California

University of California, Los Angeles

Santa Monica, California, United States, 90095

RECRUITING

United States, Florida

Moffitt Cancer Center

Tampa, Florida, United States, 33612

RECRUITING

Canada, Alberta

Cross Cancer Institute

Edmonton, Alberta, Canada,

RECRUITING

Canada, Ontario

Juravinski Cancer Centre

Hamilton, Ontario, Canada,

RECRUITING

Canada, Ontario

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, Canada,

RECRUITING

Canada, Ontario

Princess Margaret Cancer Centre

Toronto, Ontario, Canada,

RECRUITING

Canada, Quebec

Jewish General Hospital

Montreal, Quebec, Canada,

RECRUITING

Canada, Quebec

McGill University Health Centre Glen Site

Montréal, Quebec, Canada,

RECRUITING

Ireland,

St. James Hospital

Dublin, Ireland,

RECRUITING

Korea, Republic of,

National Cancer Center

Shake, Korea, Republic of,

RECRUITING

Korea, Republic of,

hospital's Book of hospital

Seoul, Korea, Republic of,

RECRUITING

Korea, Republic of,

Samsung Medical Center

Seoul, Korea, Republic of,

RECRUITING

Korea, Republic of,

Seoul National University Hospital

Seoul, Korea, Republic of,

RECRUITING

Korea, Republic of,

Severance Hospital - Yonsei University

Seoul, Korea, Republic of,