CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I Trial of CBT-1® in Combination With Doxorubicin in Patients With Locally Advanced or Metastatic, Unresectable Sarcomas Previously to Have Progressed on 150 mg/m2 or Less of Doxorubicin

Conditions
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Sarcoma

Intervention / Treatment
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* Drug: CBT-1®


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: CBT-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.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose of CBT-1® when combined with doxorubicin |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | DCR = Overall Response Rate [ORR = Complete Response + Partial Response] + Stable Disease by RECIST 1.1 | week 12 | 
| Overall Response Rate |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I, CBT-1®, Doxorubicin, Sarcoma