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

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.

Interventions

• BOLD-100 +/- FOLFOX Chemotherapy (Arm VII) · DRUG

  Arm VIIA: 500 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIB: 625 mg/m2 BOLD-100 combined with FOLFOX; Arm VIIC: FOLFOX alone

• BOLD-100 in combination with FOLFOX Chemotherapy (Arms I-VI) · DRUG

  BOLD-100 at 625 mg/m2 combined with FOLFOX Chemotherapy

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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)

Sites (24)

• University of California, Los Angeles, Santa Monica, California · COMPLETED
• Moffitt Cancer Center, Tampa, Florida · COMPLETED
• Cross Cancer Institue, Edmonton, Alberta, Canada · RECRUITING
• Juravinski Cancer Centre, Hamilton, Ontario, Canada · RECRUITING
• The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada · RECRUITING
• Princess Margaret Cancer Centre, Toronto, Ontario, Canada · RECRUITING
• Jewish General Hospital, Montreal, Quebec, Canada · RECRUITING
• McGill University Health Centre Glen Site, Montreal, Quebec, Canada · RECRUITING
• Universitatsklinikum Bonn, Bonn, Germany · RECRUITING
• University Hospital of Ulm, Ulm, Germany · RECRUITING
• Mater Miserecordiae University Hospital, Dublin, Ireland · RECRUITING
• St. James Hospital, Dublin, Ireland · RECRUITING
• St. Vincent's University Hospital, Dublin, Ireland · RECRUITING
• Fondazione IRCCS "Istituto Nazionale dei Tumori, Milan, Italy · NOT_YET_RECRUITING
• AOU L. Vanvitelli, Naples, Italy · NOT_YET_RECRUITING
• Azienda Ospedaliero Universitaria Pisana, Pisa, Italy · NOT_YET_RECRUITING
• National Cancer Center, Goyang, South Korea · RECRUITING
• Kangbuk Samsung Hospital, Seoul, South Korea · RECRUITING
• Samsung Medical Center, Seoul, South Korea · RECRUITING
• Seoul National University Hospital, Seoul, South Korea · RECRUITING
• Severance Hospital - Yonsei University, Seoul, South Korea · RECRUITING
• Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain · NOT_YET_RECRUITING
• Early Phase Unit FJD START Madrid, Madrid, Spain · NOT_YET_RECRUITING
• Hospital 12 de Octubre, Madrid, Spain · NOT_YET_RECRUITING