Sarcoma
Conditions
Keywords
Phase I, CBT-1®, Doxorubicin, Sarcoma
Brief summary
This study evaluates the combination of CBT-1® and doxorubicin for the treatment of metastatic, unresectable sarcoma in patients who have progressed after treatment with 150mg/m2 or less of doxorubicin. Participants will receive CBT-1® on days 1-7 of each 21-day cycle, as well as doxorubicin on days 5 and 6.
Interventions
DRUGCBT-1®
CBT-1®, oral, on days 1-7 of each cycle 21-day cycle. Participants will be assigned to dose level of CBT-1®: Dose level 1 - 50 mg/m2/day Dose level 2 - 100 mg/m2/day Dose level 3 - 150 mg/m2/day Dose level 4 - 200 mg/m2/day Dose level 5 - 250 mg/m2/day Dose level 6 - 300 mg/m2/day doxorubicin, 37.5 mg/m2, IV, on days 5 and 6 of each cycle Study treatment discontinued after 450 mg/m2 lifetime cumulative dose of doxorubicin reached or after 4-5 cycles completed.
Sponsors
CBA Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Locally advanced or metastatic, unresectable sarcoma that has progressed after treatment with 150 mg/m2 or less of doxorubicin or anthracycline equivalent * Measurable disease by RECIST 1.1 * ECOG performance status of ≤ 1 * Life expectancy of \> 3 months * Able to swallow pills * Adequate bone marrow and organ function as defined as: * Hemoglobin \> 9 g/dl * Absolute neutrophil count ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Total bilirubin \< 1.5 X ULN * AST(SGOT)/ALT(SGPT) ≤3 X ULN (including patients with liver metastases) * Creatinine \<1.5 X ULN * Cardiac ejection fraction \>50% (by echocardiogram or MUGA) within 15 days of enrollment * Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. * Participants must be willing and able to comply with the study scheduled visits, laboratory tests, and other procedures outlined in the protocol. * Pre-menopausal women must have a negative pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for at least six weeks after treatment discontinuation. Acceptable methods of contraception include intrauterine device (IUD), oral contraceptive, subdermal implant, double barrier and/or complete abstinence (non-periodic). * Washout period prior to Day 1 Cycle 1: * 3 weeks since last chemotherapy or therapeutic radiation therapy * 4 weeks or 3 half-lives since prior antibody-based therapy, whichever is shorter * 2 weeks since any oral anti-neoplastic or oral investigational agent * Resolution of treatment-related toxicity to \< grade 1; alopecia and cutaneous toxicity are allowed \< grade 2 * \>1 week since palliative RT * Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria
* Prior exposure to CBT-1 * Previously untreated sarcomas * Low-grade sarcomas as well as alveolar soft parts sarcoma, clear cell sarcoma, extraskeletal myxoid chondrosarcoma, well-differentiated liposarcoma, gastrointestinal stromal tumor, chordoma * Participants receiving other investigational agents * Participants with known uncontrolled brain metastases * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, chronic indwelling drains, history of interstitial pneumonitis or pulmonary fibrosis or psychiatric illness/social situations that would limit compliance with study requirements * Actively breastfeeding women unless it is interrupted during treatment and at least 6 weeks after treatment discontinuation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of CBT-1® when combined with doxorubicin | 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Recommended phase 2 dose (RP2D) of CBT-1® when combined with doxorubicin | 3 years | — |
| Disease Control Rate (DCR) of CBT-1® when combined with doxorubicin | week 12 | DCR = Overall Response Rate \[ORR = Complete Response + Partial Response\] + Stable Disease by RECIST 1.1 |
| Overall Response Rate | 3 years | — |
Other
| Measure | Time frame |
|---|---|
| Correlation of DCR, ORR and PFS to disease subtype | 3 years |
| Correlation of P-gp expression at baseline to P-gp expression after treatment | 3 years |
| Correlation of tumor response to P-gp inhibition by CBT-1® | 3 years |
| Presence of CBT-1® in tumor tissue | 3 years |
Countries
United States
Contacts
Primary ContactBeth Gudeman
Backup ContactBeth Gudeman
Outcome results
None listed