Condition or disease | Intervention/treatment | Phase |
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Platinum-Resistant Fallopian Tube Carcinoma Platinum-Resistant Ovarian Carcinoma Platinum-Resistant Primary Peritoneal Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Refractory Fallopian Tube Carcinoma Refractory Ovarian Carcinoma Refractory Primary Peritoneal Carcinoma | Drug: Anti-AXL Fusion Protein AVB-S6-500 Biological: Durvalumab | Phase 1 Phase 2 |
PRIMARY OBJECTIVES:
I. To determine toxicity profile of the combination of anti-AXL fusion protein AVB-S6-500 (AVB-S6 -500) and durvalumab therapy.
SECONDARY OBJECTIVES:
I. To estimate objective response rate to combination AVB-S6-500 and durvalumab therapy.
II. To estimate the median immune-related progression free survival (irPFS) as well as overall survival (OS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 after treatment with combination durvalumab and AVB-S6-500.
III. To investigate molecular and immunological changes associated with the combination of AVB-S6-500 and durvalumab; specifically to describe changes in T cell populations (including but not limited to CD3, CD8, CD4, FOXP3) and cell proliferation, as well as report changes in the proportion of macrophage phenotypes M1 and M2 (with phenotypic markers potentially including arginase1, CD11b, PDL-1, and CD206).
EXPLORATORY OBJECTIVES:
I. To evaluate blood and tissue based biomarkers for immune related adverse events and disease progression.
II. To investigate impact and possible sensitization of pretreatment with AVB-S6-500 monotherapy on subsequent combination of durvalumab and AVB-S6-500.
III. To evaluate for molecular and immunologic differences between pre-treatment with single agent AVB-S6-500 as compared to durvalumab.
OUTLINE: This is a phase I, dose-escalation of anti-AXL fusion protein AVB-S6-500, followed by a phase II study. In Phase I, patients receive both anti-AXL fusion protein AVB-S6-500 (intravenously [IV] over 60 minutes on days 1 and 15) and durvalumab (IV over 60 minutes on day 1) every cycle.
In Phase II, patients are randomized to 1 of 2 arms.
ARM I: Patients receive anti-AXL fusion protein AVB-S6-500 IV over 60 minutes on days 1, 15, and 29 of cycle 0, and on days 1 and 15 of subsequent cycles. Beginning cycle 1, patients also receive durvalumab IV over 60 minutes on day 1. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive durvalumab IV over 60 minutes on days 1 and 22 of cycle 0 and on day 1 of subsequent cycles. Beginning cycle 1, patients also receive anti-AXL fusion protein AVB-S6-500 IV over 60 minutes on days 1 and 15. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 6 weeks for at least 90 days.
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 36 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Randomized Phase I/II Study of AVB-S6-500 in Combination With Durvalumab (MEDI4736) in Patients With Platinum-Resistant, Recurrent Epithelial Ovarian Cancer |
Actual Study Start Date : | October 11, 2019 |
Estimated Primary Completion Date : | September 30, 2021 |
Estimated Study Completion Date : | September 30, 2021 |
Arm | Intervention/treatment |
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Experimental: Arm I (AVB-S6-500, durvalumab)
Patients receive anti-AXL fusion protein AVB-S6-500 IV over 60 minutes on days 1, 15, and 29 of cycle 0, and on days 1 and 15 of subsequent cycles. Beginning cycle 1, patients also receive durvalumab IV over 60 minutes on day 1. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
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Drug: Anti-AXL Fusion Protein AVB-S6-500
Given IV
Other Names:
Biological: Durvalumab Given IV
Other Names:
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Experimental: Arm II (durvalumab, AVB-S6-500)
Patients receive durvalumab IV over 60 minutes on days 1 and 22 of cycle 0 and on day 1 of subsequent cycles. Beginning cycle 1, patients also receive anti-AXL fusion protein AVB-S6-500 IV over 60 minutes on days 1 and 15. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
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Drug: Anti-AXL Fusion Protein AVB-S6-500
Given IV
Other Names:
Biological: Durvalumab Given IV
Other Names:
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | Female |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Serum bilirubin =< 1.5 x upper limit of normal (ULN)
Evidence of post-menopausal status or negative serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
Exclusion Criteria:
Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab or AVB-S6-500. The following are exceptions to this criterion:
Contact: Amir A Jazaeri | 713-745-1613 | aajazaeri@mdanderson.org |
United States, Texas | |
M D Anderson Cancer Center | Recruiting |
Houston, Texas, United States, 77030 | |
Contact: Amir A. Jazaeri 713-745-1613 | |
Principal Investigator: Amir A. Jazaeri |
Principal Investigator: | Amir A Jazaeri | M.D. Anderson Cancer Center |
Tracking Information | |||||
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First Submitted Date ICMJE | July 11, 2019 | ||||
First Posted Date ICMJE | July 15, 2019 | ||||
Last Update Posted Date | May 7, 2021 | ||||
Actual Study Start Date ICMJE | October 11, 2019 | ||||
Estimated Primary Completion Date | September 30, 2021 (Final data collection date for primary outcome measure) | ||||
Current Primary Outcome Measures ICMJE |
Incidence of adverse events [ Time Frame: Up to 1 year ] Safety will be monitored in the monotherapy phase and in the combination therapy phase. Will tabulate adverse events by grade, and relationship to study drug. Will estimate the proportion of subjects that discontinue treatment due to treatment-related adverse events with 90% confidence intervals. Will estimate the unacceptable toxicity rate with a 90% confidence interval.
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Original Primary Outcome Measures ICMJE | Same as current | ||||
Change History | |||||
Current Secondary Outcome Measures ICMJE | Not Provided | ||||
Original Secondary Outcome Measures ICMJE | Not Provided | ||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||
Descriptive Information | |||||
Brief Title ICMJE | AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer | ||||
Official Title ICMJE | Randomized Phase I/II Study of AVB-S6-500 in Combination With Durvalumab (MEDI4736) in Patients With Platinum-Resistant, Recurrent Epithelial Ovarian Cancer | ||||
Brief Summary | This trial studies the side effects and best dose of AVB-S6-500 when given together with durvalumab in treating patients with ovarian, fallopian tube, or primary peritoneal cancer that is resistant to platinum therapy or has come back. Immunotherapy with AVB-S6-500 and durvalumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. | ||||
Detailed Description |
PRIMARY OBJECTIVES: I. To determine toxicity profile of the combination of anti-AXL fusion protein AVB-S6-500 (AVB-S6 -500) and durvalumab therapy. SECONDARY OBJECTIVES: I. To estimate objective response rate to combination AVB-S6-500 and durvalumab therapy. II. To estimate the median immune-related progression free survival (irPFS) as well as overall survival (OS) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 after treatment with combination durvalumab and AVB-S6-500. III. To investigate molecular and immunological changes associated with the combination of AVB-S6-500 and durvalumab; specifically to describe changes in T cell populations (including but not limited to CD3, CD8, CD4, FOXP3) and cell proliferation, as well as report changes in the proportion of macrophage phenotypes M1 and M2 (with phenotypic markers potentially including arginase1, CD11b, PDL-1, and CD206). EXPLORATORY OBJECTIVES: I. To evaluate blood and tissue based biomarkers for immune related adverse events and disease progression. II. To investigate impact and possible sensitization of pretreatment with AVB-S6-500 monotherapy on subsequent combination of durvalumab and AVB-S6-500. III. To evaluate for molecular and immunologic differences between pre-treatment with single agent AVB-S6-500 as compared to durvalumab. OUTLINE: This is a phase I, dose-escalation of anti-AXL fusion protein AVB-S6-500, followed by a phase II study. In Phase I, patients receive both anti-AXL fusion protein AVB-S6-500 (intravenously [IV] over 60 minutes on days 1 and 15) and durvalumab (IV over 60 minutes on day 1) every cycle. In Phase II, patients are randomized to 1 of 2 arms. ARM I: Patients receive anti-AXL fusion protein AVB-S6-500 IV over 60 minutes on days 1, 15, and 29 of cycle 0, and on days 1 and 15 of subsequent cycles. Beginning cycle 1, patients also receive durvalumab IV over 60 minutes on day 1. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive durvalumab IV over 60 minutes on days 1 and 22 of cycle 0 and on day 1 of subsequent cycles. Beginning cycle 1, patients also receive anti-AXL fusion protein AVB-S6-500 IV over 60 minutes on days 1 and 15. Cycle 0 continues for 6 weeks and subsequent cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 weeks for at least 90 days. |
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Study Type ICMJE | Interventional | ||||
Study Phase ICMJE | Phase 1 Phase 2 |
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Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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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 |
36 | ||||
Original Estimated Enrollment ICMJE | Same as current | ||||
Estimated Study Completion Date ICMJE | September 30, 2021 | ||||
Estimated Primary Completion Date | September 30, 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 and older (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 | NCT04019288 | ||||
Other Study ID Numbers ICMJE | 2019-0149 NCI-2019-02580 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2019-0149 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | No | ||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE | Not Provided | ||||
Responsible Party | M.D. Anderson Cancer Center | ||||
Study Sponsor ICMJE | M.D. Anderson Cancer Center | ||||
Collaborators ICMJE |
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Investigators ICMJE |
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PRS Account | M.D. Anderson Cancer Center | ||||
Verification Date | May 2021 | ||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |