Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas
- Conditions
- Metastatic Soft Tissue SarcomaAdvanced Soft Tissue Sarcoma
- Registration Number
- NCT04028063
- Lead Sponsor
- University of Colorado, Denver
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br>Part One:<br><br> 1. Provision to sign and date the consent form.<br><br> 2. Stated willingness to comply with all study procedures and be available for the<br> duration of the study.<br><br> 3. Be male or female aged 18-100 years at the time of signing informed consent.<br><br> 4. Have a histological diagnosis of advanced or metastatic soft tissue sarcoma (STS)<br> (by local pathology review), not curable by surgery, for which treatment with<br> doxorubicin is deemed appropriate by the investigator.<br><br> 5. Has one of the following histologies:<br><br> - synovial sarcoma,<br><br> - malignant peripheral nerve sheath tumors,<br><br> - dedifferentiated, pleomorphic or myxoid/round cell liposarcoma,<br><br> - uterine or soft tissue leiomyosarcoma,<br><br> - malignant phylloides tumor,<br><br> - high grade undifferentiated pleomorphic sarcomas (HGUPS/MFH),<br><br> - myxofibrosarcoma,<br><br> - fibrosarcoma,<br><br> - angiosarcoma,<br><br> - spindle cell or undifferentiated sarcoma NOS,<br><br> - malignant myoepithelioma,<br><br> - malignant solitary fibrous tumor/hemangiopericytoma,<br><br> - epithelioid hemangioendothelioma,<br><br> - Any other histology or standard of care treatment not specifically addressed<br> will be reviewed by the principal investigator and pathologist for final<br> determination of eligibility.<br><br> 6. Have measurable or nonmeasurable but evaluable disease as defined by the Response<br> Evaluation Criteria in Solid Tumors (RECIST 1.1). Tumors within a previously<br> irradiated field will be designated as nontarget lesions unless progression is<br> documented or a biopsy is obtained to confirm persistence at least 90 days following<br> completion of radiotherapy.<br><br> 7. Have received 0 or 1 prior systemic therapies for metastatic sarcoma and NO prior<br> anthracyclines or checkpoint inhibitors.<br><br> 8. Adequate organ function as defined in protocol.<br><br> Absolute neutrophil count (ANC) =1,000 /mcL Platelets =100,000 / mcL Hemoglobin =8<br> g/dL without EPO dependency<br><br> Serum creatinine OR Measured or calculated creatiniecclearance<br><br> =1.5 X upper limit of normal (ULN) OR =60 mL/min for subject with creatinine levels<br> > 1.5 X institutional ULN<br><br> Serum total bilirubin = 1.5 X ULN OR Direct bilirubin = ULN for subjects with total<br> bilirubin levels > 1.5 ULN Exception: Subjects with known history of Gilbert's<br> disease should be = 1.5 X of the patient's prior baseline AST (SGOT) and ALT (SGPT)<br> =2.5 X ULN OR = 5 X ULN for subjects with liver metastases Albumin >2.5 mg/dL<br><br> International Normalized Ratio (INR) or Prothrombin Time (PT)<br><br> =1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is<br> within therapeutic range of intended use of anticoagulants<br><br> Activated Partial Thromboplastin Time (aPTT) =1.5 X ULN unless subject is receiving<br> anticoagulant therapy as long as PT or PTT is within therapeutic range of intended<br> use of anticoagulants<br><br> Creatinine clearance should be calculated per institutional standard.<br><br> 9. ECOG performance status of 0 or 1.<br><br> 10. Patients must consent and be willing to undergo tumor core needle biopsies at two<br> timepoints: 1. Baseline, 2. Cycle 2 Day 5; a third biopsy for off-study/progression<br> is optional but advised. At least one tumor site must be amenable to biopsy in the<br> judgment of the interventional radiologist.<br><br> 11. Female subjects of childbearing potential should have a negative urine or serum<br> pregnancy within 72 hours prior to receiving the first dose of study medication. If<br> the urine test is positive or cannot be confirmed as negative, a serum pregnancy<br> test will be required.<br><br> 12. Females of child bearing potential that are sexually active must agree to either<br> practice 2 medically accepted highly effective methods of contraception at the same<br> time or abstain from heterosexual intercourse from the time of signing the informed<br> consent through 120 days after the last dose of study drug. See Appendix B for<br> protocol-approved highly effective methods of contraceptive combinations. Subjects<br> of childbearing potential are those who have not been surgically sterilized or have<br> not been free from menses for > 1 year.<br><br> - Negative test for pregnancy is required of females of child-bearing potential.<br> A female of child-bearing potential is any woman, regardless of sexual<br> orientation or whether they have undergone tubal ligation, who meets the<br> following criteria: 1. Has not undergone a hysterectomy or bilateral<br> oophorectomy; or 2. Has not been naturally postmenopausal for at least 24<br> consecutive months (ie, has had menses at any time in the preceding 24<br> consecutive months or 730 days.)<br><br> - Conception while on treatment must be avoided.<br><br> 13. Male subjects should agree to use an adequate method of contraception starting with<br> the first dose of study therapy through 120 days after the last dose of study<br> therapy. Prior history of vasectomy does NOT replace requirement for contraceptive<br> use.<br><br> 14. Subjects must either possess or undergo placement of central venous catheter,<br> including pheresis or trifusion catheter, PICC line, or port.<br><br>Part Two: In order to be eligible to participate in this study, an individual must meet<br>all of the following criteria:<br><br> 1. Provision to sign and date the consent form.<br><br> 2. Stated willingness to comply with all study procedures and be available for the<br> duration of the study.<br><br> 3. Be male or female aged 18-100 years at the time of signing informed consent.<br><br> 4. Have a histological diagnosis of advanced or metastatic soft tissue sarcoma (STS)<br> (by local pathology review), not curable by surgery, for which treatment with<br> doxorubicin is deemed appropriate by the investigator.<br><br> 5. Has one of the following histologies:<br><br> - synovial sarcoma,<br><br> - malignant peripheral nerve sheath tumors,<br><br> - dedifferentiated, pleomorphic or myxoid/round cell liposarcoma,<br><br> - uterine or soft tissue leiomyosarcoma,<br><br> - malignant phylloides tumor,<br><br> - high grade undifferentiated pleomorphic sarcomas (HGUPS/MFH),<br><br> - myxofibrosarcoma,<br><br> - fibrosarcoma,<br><br> - angiosarcoma,<br><br> - spindle cell or undifferentiated sarcoma NOS,<br><br> - malignant myoepithelioma,<br><br> - malignant solitary fibrous tumor/hemangiopericytoma,<br><br> - epithelioid hemangioendothelioma,<br><br> - Any other histology or standard of care treatment not specifically addressed<br> will be reviewed by the principal investigator in consultation with pathology<br> as needed for final determination of eligibility.<br><br> 6. Have measurable or nonmeasurable but evaluable disease as defined by the Response<br> Evaluation Criteria in Solid Tumors (modified RECIST 1.1). Tumors within a<br> previously irradiated field will be designated as nontarget lesions unless<br> progression is documented or a biopsy is obtained to confirm persistence at least 90<br> days following completion of radiotherapy.<br><br> 7. Have received any number of prior systemic therapies for metastatic sarcoma but NO<br> prior anthracyc
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Determine the progression-free survival rate
- Secondary Outcome Measures
Name Time Method Determine the overall response rate;Determine the clinical benefit rate;Determine the duration of response;Determine the incidence of adverse events