Sarcoma, Sarcomas, Sarcoma, Soft-tissue, Sarcoma,Soft Tissue
Conditions
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.
Interventions
DRUGBOLD-100
BOLD-100 in combination with Doxorubicin (Escalation)
DRUGDoxorubicin 75 mg/m^2
BOLD-100 in combination with Doxorubicin (Escalation)
Sponsors
University Health Network, Toronto
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent in accordance with federal, local, and institutional guidelines. 2. Age \> 18 years. 3. Patients must have histologically confirmed locally advanced/unresectable or metastatic soft tissue sarcoma of limited subtype LMS, DDLPS and UPS (including Myxofibrosarcoma-MFS). 4. Patients be systemic treatment naïve, with incurable, advanced or metastatic disease. 5. Patient must have measurable disease as defined by RECIST 1.1. 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Adequate hematopoietic function: 1. total white blood cell (WBC) count ≥2000/mm3. 2. absolute neutrophil count (ANC) ≥1500/mm3. 3. platelet count ≥100,000/mm3. 8. Adequate hepatic function: 1. 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). 2. 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. 9. Adequate renal function defined as \<1.5x upper limits of normal 10. 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. 11. Female patients of childbearing potential must agree to use two methods of contraception (including one highly effective and one effective method of contraception) and have a negative serum pregnancy test at 72 hours prior to receiving the first dose of study medication. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
Exclusion criteria
Subjects should not enter the study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant Quality of Life | pre-dose, Cycle 2 Day1, Cycle 7 Day 1, Cycle 12 Day 1 (21 day cycles) | 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. |
| The incidence of dose limiting toxicities (DLTs) | Entire duration of Cycle 1 (21 day cycle) | — |
| The rate of Adverse Events (AE) | time the consent form is signed through 12 months following cessation of treatment | 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 |
| Rate of toxicities | time the consent form is signed through 12 months following cessation of treatment. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | time the consent form is signed through treatment completion, up to 4-6 weeks after progression if applicable | 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 |
| 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 (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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Correlate cellular morphology and biomarker changes | through study completion, an average of 1 year | Correlate cellular morphology and biomarker changes on sarcoma biopsy specimens compared to archival tissue. Immunohistochemical expression/localization of GRP78. |
| Correlate immune signatures and expression of GRP78 levels | through study completion, an average of 1 year | Correlate immune signatures and expression of GRP78 levels in leukocytes in patients' blood with response rate using non-parametric Wilcoxon rank sum. |
Countries
Canada
Contacts
Primary ContactAlbiruni Razak, MD
Outcome results
None listed