BOLD-100 Plus Doxorubicin in Advanced Soft Tissue Sarcomas

NCT07027423 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: BOLDSARC-01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

A Phase 1b, non-randomized, single-institution trial designed to assess the safety, tolerability and the highest dose with acceptable toxicity (RP2D) of BOLD-100 in combination with doxorubicin in patients diagnosed with advanced soft tissue sarcomas. The trial is divided into two phases: an initial dose-escalation phase for BOLD-100, followed by a dose-expansion phase based on the recommended dose for Phase 2. In the dose-escalation phase, we plan to enroll 12-15 patients, with an additional 17 patients in the dose-expansion phase. Participants will receive BOLD-100 intravenously on Days 1 and 8 of a 21-day cycle, in combination with doxorubicin (75 mg/m², intravenous) administered on Day 1 of each 21-day cycle for up to six cycles. Participants will continue to receive BOLD-100 for as long as the cancer is not getting worse, The maximum cycles of doxorubicin are 6 cycles. Participants will undergo a screening assessment prior to the start treatment to determine eligibility for enrollment. Treatment will commence on Day 1 and will continue until the protocol-defined criteria for treatment withdrawal are met. Disease response will be assessed using CT or MRI scans, starting at 12 weeks after the initiation of treatment and continuing every 12 weeks until withdrawal. Upon treatment discontinuation or study withdrawal, a post-treatment assessment will be conducted at end of treatment and at 30 days of the last BOLD-100 dose, with follow-up visits scheduled every 3 months thereafter.

Conditions

Sarcoma, Soft-tissue; Sarcoma; Sarcoma,Soft Tissue; Sarcomas

Outcome Measures

Primary Outcomes (4)

• The incidence of dose limiting toxicities (DLTs)

  Entire duration of Cycle 1 (21 day cycle)

• The rate of Adverse Events (AE)

  The rate of Adverse Events (AE) characterized by type, frequency, severity graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0

  time the consent form is signed through 12 months following cessation of treatment

• Rate of toxicities

  Rate of toxicities as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0, adverse events (AEs), serious AEs (SAEs), dose interruptions and assessment.

  time the consent form is signed through 12 months following cessation of treatment.

• Participant Quality of Life

  Assessed using EORTC QLQ-C30 (European Organization For Research And Treatment Of Cancer, Core Quality of Life Questionnaire). With scores from 0 to 100. A high scale score represents a higher response level.

  pre-dose, Cycle 2 Day1, Cycle 7 Day 1, Cycle 12 Day 1 (21 day cycles)

Secondary Outcomes (4)

• Progression-free survival (PFS)

  time the consent form is signed through treatment completion, up to 4-6 weeks after progression if applicable

• Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100

  During Cycle 1 pre-dose, 1hour, 2hours and 48hours post-dose, through Cycle 2 pre-dose (21 day cycles)

• Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100

  During Cycle 1 pre-dose, 1hour, 2hours and 48hours post-dose, through Cycle 2 pre-dose (21 day cycles)

• Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100

  During Cycle 1 pre-dose, 1hour, 2hours and 48hours post-dose, through Cycle 2 pre-dose (21 day cycles)

Other Outcomes (2)

• Correlate cellular morphology and biomarker changes

  through study completion, an average of 1 year

• Correlate immune signatures and expression of GRP78 levels

  through study completion, an average of 1 year

Study Arms (5)

BOLD-100 and Doxorubicin Dose Level -1

EXPERIMENTAL

Escalation phase DL-1 - BOLD-100 230mg/m\^2 + Doxorubicin

Drug: BOLD-100; Drug: Doxorubicin 75 mg/m^2

BOLD-100 and Doxorubicin Dose Level 1

EXPERIMENTAL

Escalation phase DL1 - BOLD-100 420mg/m\^2 + Doxorubicin

Drug: BOLD-100; Drug: Doxorubicin 75 mg/m^2

BOLD-100 and Doxorubicin Dose Level 2

EXPERIMENTAL

Escalation phase DL2 - BOLD-100 500mg/m\^2 + Doxorubicin

Drug: BOLD-100; Drug: Doxorubicin 75 mg/m^2

BOLD-100 and Doxorubicin Dose Level 3

EXPERIMENTAL

Escalation phase DL3 - BOLD-100 625mg/m\^2 + Doxorubicin

Drug: BOLD-100; Drug: Doxorubicin 75 mg/m^2

BOLD-100 and Doxorubicin

EXPERIMENTAL

Exapsnion: BOLD-100 (RP2D) and Doxorubicin

Drug: BOLD-100; Drug: Doxorubicin 75 mg/m^2

Interventions

BOLD-100 DRUG

BOLD-100 in combination with Doxorubicin (Escalation)

BOLD-100 and Doxorubicin Dose Level -1; BOLD-100 and Doxorubicin Dose Level 1; BOLD-100 and Doxorubicin Dose Level 2; BOLD-100 and Doxorubicin Dose Level 3

Doxorubicin 75 mg/m^2 DRUG

BOLD-100 in combination with Doxorubicin (Escalation)

BOLD-100 and Doxorubicin Dose Level -1; BOLD-100 and Doxorubicin Dose Level 1; BOLD-100 and Doxorubicin Dose Level 2; BOLD-100 and Doxorubicin Dose Level 3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent in accordance with federal, local, and institutional guidelines.
• Age \> 18 years.
• Patients must have histologically confirmed locally advanced/unresectable or metastatic soft tissue sarcoma of limited subtype LMS, DDLPS and UPS (including Myxofibrosarcoma-MFS).
• Patients be systemic treatment naïve, with incurable, advanced or metastatic disease.
• Patient must have measurable disease as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematopoietic function:
• total white blood cell (WBC) count ≥2000/mm3.
• absolute neutrophil count (ANC) ≥1500/mm3.
• platelet count ≥100,000/mm3.
• Adequate hepatic function:
• Bilirubin \<2 times the upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3 times ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 X ULN. In the case of known (radiological and/or biopsy documented) liver metastasis, ALT/AST \<5.0 X ULN is acceptable.
• Adequate renal function defined as \<1.5x upper limits of normal
• Cardiac function: A normal left ventricular ejection fraction (LVEF) of \> 50% as evidenced by an echocardiogram or nuclear medicine study performed within 28 days of the proposed study commencement.

You may not qualify if:

• Patient is pregnant or lactating.
• Radiation (except planned or ongoing palliative radiation outside of the region of measurable disease), chemotherapy, immunotherapy, any other systemic anticancer therapy, or participation in an investigational anti-cancer study ≤3 weeks prior to initiation of therapy.
• Major surgery within 4 weeks before initiation of therapy.
• Prior systemic therapy.
• Unstable cardiovascular function:
• symptomatic ischemia, or.
• uncontrolled clinically significant conduction abnormalities (e.g., ventricular tachycardia on anti-arrhythmic is excluded and 1st degree AV block or asymptomatic LAFB/RBBB will not be excluded) or.
• congestive heart failure (CHF) of NYHA Class ≥3, or.
• myocardial infarction (MI) within 3 months of initiation of therapy.
• Active, ongoing or uncontrolled active infection within one week prior to first dose.
• Malignancies other than disease under study within 2 years prior to Cycle 1, Day 1, except for those with a negligible risk of metastasis or death (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer, or ductal carcinoma in situ). Prior chemotherapy is allowed apart from regimens that contained anthracycline based therapies.
• Known to be HIV seropositive.
• Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or hepatitis B virus (HBV) surface antigen (HBsAg).
• Patients with active CNS malignancy. Asymptomatic small lesions are not considered active. Treated lesions may be considered inactive if they are stable for at least 3 months.
• Serious psychiatric or medical conditions that could interfere with treatment.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

UHN- Princess Margaret Cancer Center

Toronto, Ontario, M5G 1Z5, Canada

Location

MeSH Terms

Conditions

Sarcoma

Interventions

KP 1339; Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Albiruni Razak, MD

CONTACT

416 586 5371; Albiruni.razak@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2025
• First Posted: June 18, 2025
• Study Start: March 30, 2026
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): January 29, 2027
• Last Updated: December 1, 2025

Record last verified: 2025-11

Locations

CA (1)