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

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03002805
• Other study ID #: STS-1701
• Status: Recruiting
• Phase: Phase 1
• Start date: March 29, 2018
• Est. completion date: September 2020

Study information

• Verified date: August 2019
• Source: CBA Research
• Contact: Beth Gudeman
• Phone: 859-266-5757
• Email: bethg[@]cba-1.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: September 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Sarcoma

Intervention

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.

Locations

Country	Name	City	State
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Mayo Clinic	Jacksonville	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Sarcoma Oncology Research Center	Santa Monica	California
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
CBA Research

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Correlation of DCR, ORR and PFS to disease subtype		3 years
Other	Correlation of P-gp expression at baseline to P-gp expression after treatment		3 years
Other	Correlation of tumor response to P-gp inhibition by CBT-1®		3 years
Other	Presence of CBT-1® in tumor tissue		3 years
Primary	Maximum tolerated dose of CBT-1® when combined with doxorubicin		3 years
Secondary	Recommended phase 2 dose (RP2D) of CBT-1® when combined with doxorubicin		3 years
Secondary	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
Secondary	Overall Response Rate		3 years