BOLD-100 Plus Doxorubicin in Advanced Soft Tissue Sarcomas
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity Health Network, Toronto
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Sequential
Treatments tested in this trial
BOLD-100
DrugBOLD-100 in combination with Doxorubicin (Escalation)
Doxorubicin 75 mg/m^2
DrugBOLD-100 in combination with Doxorubicin (Escalation)
BOLD-100
DrugBOLD-100 in combination with Doxorubicin (Expansion)
Doxorubicin 75 mg/m^2
DrugBOLD-100 in combination with Doxorubicin (Expansion)
Treatment groups
32 Participants
are divided into 5 treatment groupsGroup A: BOLD-100 and Doxorubicin Dose Level -1Experimental treatment 2 interventions
Group B: BOLD-100 and Doxorubicin Dose Level 1Experimental treatment 2 interventions
Group C: BOLD-100 and Doxorubicin Dose Level 2Experimental treatment 2 interventions
Group D: BOLD-100 and Doxorubicin Dose Level 3Experimental treatment 2 interventions
Group E: BOLD-100 and DoxorubicinExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
The incidence of dose limiting toxicities (DLTs)
Time frame
Entire duration of Cycle 1 (21 day cycle)2
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 frame
time the consent form is signed through 12 months following cessation of treatment3
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 frame
time the consent form is signed through 12 months following cessation of treatment.4
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.
Time frame
pre-dose, Cycle 2 Day1, Cycle 7 Day 1, Cycle 12 Day 1 (21 day cycles)Secondary outcomes
1
Progression-free survival (PFS)
Progression-free survival (PFS), response rate using RECIST v 1.1, clinical benefit rate (CR, PR, SD \>16 weeks) using the Kaplan Meier method to estimate with corresponding 95% CI
Time frame
time the consent form is signed through treatment completion, up to 4-6 weeks after progression if applicable2
Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100
Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100 (in the first 3 patients per dose level) using Peak Plasma Concentration (Cmax), which will be compared to single agent population PK of doxorubicin and BOLD-100.
Time frame
During Cycle 1 pre-dose, 1hour, 2hours and 48hours post-dose, through Cycle 2 pre-dose (21 day cycles)3
Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100
Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100 (in the first 3 patients per dose level) using area under the plasma concentration versus time curve (AUC), which will be compared to single agent population PK of doxorubicin and BOLD-100.
Time frame
During Cycle 1 pre-dose, 1hour, 2hours and 48hours post-dose, through Cycle 2 pre-dose (21 day cycles)4
Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100
Analysis of pharmacokinetic parameters of doxorubicin and BOLD-100 (in the first 3 patients per dose level) using time to peak drug concentration (Tmax), which will be compared to single agent population PK of doxorubicin and BOLD-100.
Time frame
During Cycle 1 pre-dose, 1hour, 2hours and 48hours post-dose, through Cycle 2 pre-dose (21 day cycles)Other outcomes
1
Correlate cellular morphology and biomarker changes
Correlate cellular morphology and biomarker changes on sarcoma biopsy specimens compared to archival tissue. Immunohistochemical expression/localization of GRP78.
Time frame
through study completion, an average of 1 year2
Correlate immune signatures and expression of GRP78 levels
Correlate immune signatures and expression of GRP78 levels in leukocytes in patients' blood with response rate using non-parametric Wilcoxon rank sum.
Time frame
through study completion, an average of 1 yearSponsors and contacts
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Source ClinicalTrials.gov
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