Clinical trial NCT03002805: CBT-1® in Combination With Doxorubicin in Patients With Metastatic, Unresectable Sarcomas Who Previously Progressed on Doxorubicin
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Sarcoma
Keywords: Phase I
CBT-1®
Doxorubicin
Sarcoma
Lead sponsor: CBA Research
Sponsor class: INDUSTRY
First posted: 2016-12-26
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose of CBT-1® when combined with doxorubicin
timeFrame: 3 years
Secondary outcomes:
measure: Recommended phase 2 dose (RP2D) of CBT-1® when combined with doxorubicin
timeFrame: 3 years
measure: Disease Control Rate (DCR) of CBT-1® when combined with doxorubicin
timeFrame: week 12
measure: Overall Response Rate
timeFrame: 3 years
Other outcomes:
measure: Correlation of DCR, ORR and PFS to disease subtype
timeFrame: 3 years
measure: Correlation of P-gp expression at baseline to P-gp expression after treatment
timeFrame: 3 years
measure: Correlation of tumor response to P-gp inhibition by CBT-1®
timeFrame: 3 years
measure: Presence of CBT-1® in tumor tissue
timeFrame: 3 years
Locations:
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
References:
citation: Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.