Condition or disease | Intervention/treatment | Phase |
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Metastatic Soft Tissue Sarcoma Advanced Soft Tissue Sarcoma | Drug: doxorubicin with AGEN1884 and AGEN2034 | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 28 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | An Open-Label, Phase II Efficacy Trial of Doxorubicin in Combination With Dual Checkpoint Blockade Using AGEN1884 and AGEN2034 for Advanced or Metastatic Soft Tissue Sarcomas |
Actual Study Start Date : | January 28, 2020 |
Estimated Primary Completion Date : | November 24, 2021 |
Estimated Study Completion Date : | November 2022 |
Arm | Intervention/treatment |
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Experimental: doxorubicin with AGEN1884 and AGEN2034
Doxorubicin with dual checkpoint blockade with anti-CTLA-4 antibody AGEN1884 and anti-PD-1 antibody AGEN2034. Doxorubicin dosing is standard at 75 mg/m2 via Bolus with prior Dexrazoxane. AGEN2034 - 300 mg IV over 60min with infusion pump. AGEN1884 - 1 mg/kg IV over 90 min (-10 /+20 min) with infusion pump, within 30 minutes (0 / +20) of completion of AGEN2034.
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Drug: doxorubicin with AGEN1884 and AGEN2034
The first cycle of treatment will consist of AGEN2034 and AGEN1884 alone. Beginning with Cycle 2, doxorubicin will be administered every 21 days for a maximum of 6 cycles (Cycles 2-7) with appropriate premedications and pegfilgrastim growth factor support. Doxorubicin will be administered as bolus infusion on day 1 with dexrazoxane cardioprotection. Patients must have central line access for this protocol, including pheresis or trifusion catheter, PICC line, or port. AGEN2034 will be administered every cycle (every 21 days) up to two years. AGEN1884 will be administered every other cycle (Cycle 1, 3, 5, and 7) with maximum of 4 infusions.
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Ages Eligible for Study: | 18 Years to 100 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Has one of the following histologies:
Females of child bearing potential that are sexually active must agree to either practice 2 medically accepted highly effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 120 days after the last dose of study drug. See Appendix B for protocol-approved highly effective methods of contraceptive combinations. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
Exclusion Criteria:
Contact: Chelsey Cartwright | (720)848-0741 | CHELSEY.CARTWRIGHT@CUANSCHUTZ.EDU |
United States, Colorado | |
University of Colorado Hospital | Recruiting |
Aurora, Colorado, United States, 80045 | |
Contact: Chelsey Cartwright 720-848-0741 CHELSEY.CARTWRIGHT@CUANSCHUTZ.EDU | |
Principal Investigator: Breelyn Wilky |
Tracking Information | |||||
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First Submitted Date ICMJE | July 17, 2019 | ||||
First Posted Date ICMJE | July 22, 2019 | ||||
Last Update Posted Date | March 8, 2021 | ||||
Actual Study Start Date ICMJE | January 28, 2020 | ||||
Estimated Primary Completion Date | November 24, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Determine the progression-free survival rate [ Time Frame: 6 months ] Determine the progression-free survival rate at 6 months of combination therapy with doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||
Current Other Pre-specified Outcome Measures |
Measure changes in tumor-infiltrating and circulating immune cells [ Time Frame: 3 years ] To measure the change in proportion of various immune cells in tumor biopsies and peripheral blood samples and correlate with response outcomes as a result of combination therapy with doxorubicin, AGEN1884, and AGEN2034 in anthracycline-naïve patients with advanced or metastatic soft tissue sarcomas.
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Original Other Pre-specified Outcome Measures | Same as current | ||||
Descriptive Information | |||||
Brief Title ICMJE | Doxorubicin Plus Dual Checkpoint Blockade for Soft Tissue Sarcomas | ||||
Official Title ICMJE | An Open-Label, Phase II Efficacy Trial of Doxorubicin in Combination With Dual Checkpoint Blockade Using AGEN1884 and AGEN2034 for Advanced or Metastatic Soft Tissue Sarcomas | ||||
Brief Summary | This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in. The overall objective is to determine the efficacy of combination doxorubicin with dual checkpoint blockade with anti-CTLA-4 antibody AGEN1884 and anti-PD-1 antibody AGEN2034. The investigators will estimate the progression-free survival rate at 6 months (PFS6mo) of doxorubicin plus AGEN1884/AGEN2034 in comparison to historical PFS6mo with doxorubicin monotherapy, calculated as the mean from two large randomized Phase 3 clinical trials. | ||||
Detailed Description | The primary endpoint for the study is PFS6mo by RECIST 1.1. The sample size calculation is based on a Simon Two-Stage design with incorporation of early stopping rules for safety and futility (See section 9 for statistical considerations). The Investigators will enroll up to 35 patients on the study to obtain 28 evaluable patients for the primary endpoint. Safety of the combination will be evaluated after the first six patients complete the DLT observation period of 9 weeks. This lengthy DLT period is designed to capture safety and toxicity profile, understanding that immune-related toxicities from checkpoint inhibitors may not emerge immediately. This will also ensure adequate evaluation of potential cardiac and hepatic toxicity from combination doxorubicin and checkpoint inhibitor therapy. If two or more patients experience DLT in the initial safety lead-in cohort, the regimen will be declared intolerable. Any patients who do not complete study therapy through the 9-week DLT observation period for any reasons other than toxicity will be replaced for safety lead-in assessment. If fewer than two patients experience DLT, the investigators will proceed to expansion to complete enrollment of 15 patients in Stage 1. Following enrollment of stage one, accrual will pause for analysis of efficacy. If 6 or fewer of the 15 patients are progression-free at 6 months, the investigators will halt the study for futility. If 7 or more patients are free from progression, then the investigators will proceed with enrollment of 13 additional patients to complete stage 2. the investigators are powered to detect improvement in 6-month PFS rate to 63.4% with the combination over the 43.4% historical PFS6mo. | ||||
Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 2 | ||||
Study Design ICMJE | Allocation: N/A Intervention Model: Single Group Assignment Intervention Model Description: This is an open-label, non-randomized, single-institution, single arm Phase II study conducted using a Simon two-stage design with an additional safety lead-in. Masking: None (Open Label)Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE | Drug: doxorubicin with AGEN1884 and AGEN2034
The first cycle of treatment will consist of AGEN2034 and AGEN1884 alone. Beginning with Cycle 2, doxorubicin will be administered every 21 days for a maximum of 6 cycles (Cycles 2-7) with appropriate premedications and pegfilgrastim growth factor support. Doxorubicin will be administered as bolus infusion on day 1 with dexrazoxane cardioprotection. Patients must have central line access for this protocol, including pheresis or trifusion catheter, PICC line, or port. AGEN2034 will be administered every cycle (every 21 days) up to two years. AGEN1884 will be administered every other cycle (Cycle 1, 3, 5, and 7) with maximum of 4 infusions.
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Study Arms ICMJE | Experimental: doxorubicin with AGEN1884 and AGEN2034
Doxorubicin with dual checkpoint blockade with anti-CTLA-4 antibody AGEN1884 and anti-PD-1 antibody AGEN2034. Doxorubicin dosing is standard at 75 mg/m2 via Bolus with prior Dexrazoxane. AGEN2034 - 300 mg IV over 60min with infusion pump. AGEN1884 - 1 mg/kg IV over 90 min (-10 /+20 min) with infusion pump, within 30 minutes (0 / +20) of completion of AGEN2034.
Intervention: Drug: doxorubicin with AGEN1884 and AGEN2034
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Publications * | Not Provided | ||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||
Recruitment Status ICMJE | Recruiting | ||||
Estimated Enrollment ICMJE |
28 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | November 2022 | ||||
Estimated Primary Completion Date | November 24, 2021 (Final data collection date for primary outcome measure) | ||||
Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 100 Years (Adult, Older Adult) | ||||
Accepts Healthy Volunteers ICMJE | No | ||||
Contacts ICMJE |
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Listed Location Countries ICMJE | United States | ||||
Removed Location Countries | |||||
Administrative Information | |||||
NCT Number ICMJE | NCT04028063 | ||||
Other Study ID Numbers ICMJE | 19-0554.cc P30CA046934 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Responsible Party | University of Colorado, Denver | ||||
Study Sponsor ICMJE | University of Colorado, Denver | ||||
Collaborators ICMJE |
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Investigators ICMJE | Not Provided | ||||
PRS Account | University of Colorado, Denver | ||||
Verification Date | March 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |