July 23, 2018
|
July 31, 2018
|
September 29, 2021
|
June 30, 2021
|
August 31, 2024 (Final data collection date for primary outcome measure)
|
- Maximum tolerated dose (MTD) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: Completion of the enrollment and treatment of all patients (estimated to be approximately 26 months) ]
- The study will employ the Bayesian optimal interval design (BOIN) to find the MTD.
- Select as the MTD the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, select the higher dose level when the isotonic estimate is lower than the target toxicity rate and select the lower dose level when the isotonic estimate is greater than or equal to the target toxicity rate.
- Dose limiting toxicities (DLTs) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: Through completion of 1st cycle for all patients (estimated to be 13 months) ]
-Hematologic DLT any of the following that occur during the 1st cycle (C) that are possibly (pos), probably (prob), or definitely (def) related to the study treatment:
- Grade (Gr.) 4 neutropenia or thrombocytopenia > 7 day
- Febrile neutropenia w/ temp > 38.5 °C
- Gr. 4 anemia or Gr. 4 thrombocytopenia which requires transfusion therapy on more than 2 occasions in 7 days
- Gr. thrombocytopenia w/ bleeding
Non-hematologic DLT is any pos, prob, or def related Gr. 3 or grade 4 non-hematologic toxicity that occurs during C1 with the following exceptions:
- Gr. 3/4 nausea/vomiting/anorexia that returns to Gr. 1 prior to the start of C2
- Gr. 3 nausea/vomiting or diarrhea < 72 hours with adequate antiemetic and other supportive care starting with C2
- Gr. 3 triglycerides will only be considered a DLT for patients who have grade 3 in spite of appropriate lipid lowering drug therapy
- Gr. 3 rash (patients who have received 2 weeks of supportive care treatment w/ no improvement)
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by treatment discontinuation [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of dose interruption/reductions [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by use of supportive therapies [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of hospital admissions [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of deaths [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
|
- Maximum tolerated dose (MTD) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: Completion of the enrollment and treatment of all patients (estimated to be approximately 26 months) ]
- The study will employ the Bayesian optimal interval design (BOIN) to find the MTD.
- Select as the MTD the dose for which the isotonic estimate of the toxicity rate is closest to the target toxicity rate. If there are ties, select the higher dose level when the isotonic estimate is lower than the target toxicity rate and select the lower dose level when the isotonic estimate is greater than or equal to the target toxicity rate.
- Dose limiting toxicities (DLTs) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: Through completion of 1st cycle for all patients (estimated to be 13 months) ]
-Hematologic DLT is any of the following that occur during the 1st cycle that are possibly, probably, or definitely related to the study treatment in combination with chemotherapy:
- Grade 4 neutropenia > 7 day duration
- Febrile neutropenia of any duration with temperature > 38.5 °C
- Grade 4 anemia or Grade 4 thrombocytopenia which requires transfusion therapy on more than 2 occasions in 7 days
Non-hematologic DLT is any possibly, probably, or definitely related grade 3 or grade 4 non-hematologic toxicity that occurs during the 1st cycle with the following specific exceptions:
- Grade 3/4 nausea, vomiting, or anorexia that returns to Grade 1 prior to the start of cycle 2
- Grade 3 triglycerides will only be considered a DLT for patients who have grade 3 in spite of appropriate lipid lowering drug therapy
- Grade 3 rash will only be considered a DLT for patients who have received 2 weeks of supportive care treatment with no improvement
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by treatment discontinuation [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of dose interruption/reductions [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by use of supportive therapies [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of hospital admissions [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
- Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of deaths [ Time Frame: Through completion of treatment (estimated to be 14 months) ]
|
|
- Objective clinical response (cOR) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: At the time of interval debulking (approximately 9-12 weeks) ]
-cOR = clinical response seen at the time of surgery with no visible disease
- Pathological complete response (pCR) at the time of interval debulking surgery of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: At the time of interval debulking (approximately 9-12 weeks) ]
-pCR = pathological response seen by the pathology at the time of surgery with treatment effect and no disease seen microscopically
- Progression-free survival (PFS) at 1 year after debulking surgery of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: 1 year after debulking surgery (approximately 64 weeks) ]
- PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
- Progression-free survival (PFS) at 2 years after debulking surgery of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: 2 years after debulking surgery (approximately 116 weeks) ]
- PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
- Overall survival (OS) by long-term follow-up of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance [ Time Frame: 5 years after completion of treatment (approximately 74 months) ]
-OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.
|
Same as current
|
Not Provided
|
Not Provided
|
|
Paclitaxel + Carboplatin With AVB-S6-500 in Women With Stage III or IV Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Receiving Neoadjuvant Chemotherapy
|
Phase IB Study of Paclitaxel + Carboplatin With AVB-S6-500 in Women With Stage III or IV Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Receiving Neoadjuvant Chemotherapy
|
The receptor tyrosine kinase AXL is a pathway that plays a crucial role in metastasis and chemoresistance. Overexpression of AXL has been associated with metastasis, recurrence, and chemoresistance in various cancer including ovarian cancer[16, 17]}. Targeting AXL is an attractive approach because it is overexpressed among patients with epithelial ovarian cancer and strongly associated with advanced stages, high grade cancer and shorter median survival time. AVB-S6-500 is a potent AXL inhibitor by binding to the ligand Gas6. Pre-clinical studies found that AVB-S6-500 was efficacious in ovarian cancer xenograft tumor models. Interventions which would increase the proportion of patients achieving pCR in this patient population could impact survival favorably and are of interest for study.
|
Not Provided
|
Interventional
|
Phase 1
|
Allocation: N/A Intervention Model: Single Group Assignment Masking: None (Open Label) Primary Purpose: Treatment
|
- Epithelial Ovarian Cancer
- Primary Peritoneal Carcinoma
- Fallopian Tube Cancer
|
- Drug: AVB-S6-500
AVB-S6-500 is supplied by Aravive Biologics
- Drug: Paclitaxel
Commercially available
Other Name: Taxol
- Drug: Carboplatin
Commercially available
Other Name: Paraplatin
- Procedure: Tissue from Diagnostic Laparoscopy
-For patients scheduled to undergo a diagnostic laparoscopy for tissue diagnosis prior to neoadjuvant chemotherapy, a tissue biopsy section from the ovary or an intra-abdominal implant will be performed
- Procedure: Tissue from Core biopsy
-Standard of care procedure but research specimens will be collected
- Procedure: Interval Debulking
- Standard of Care
- Research tissue samples will be collected
- Procedure: Peripheral blood
-Before initiation of neoadjuvant chemotherapy and at the time of interval debulking surgery either pre-operatively, intraoperatively, or post-operatively.
- Procedure: Ascites collection
-A total of 25-100ml of ascites will be collected prior to chemotherapy treatment, if available.
|
Experimental: AVB-S6-500 + Paclitaxel + Carboplatin
- Paclitaxel will be given intravenously at a dose of 175 mg/m^2 on an outpatient basis over 3 hours on Day 1 of each 21-day cycle
- Carboplatin will be given intravenously at a dose of AUC 6 over 30 minutes on Day 1 of each cycle of chemotherapy
- AVB-S6-500 will be given at doses based on the dose escalation schema
- The investigators will continue dosing AVB-S6-500 until 1 week prior to surgery and continuing after surgery. Maintenance dosing q2 weeks will begin with Cycle 7A/7B and be given every 2 weeks for 12 months through Cycle 19 (total of 13 maintenance cycles).
Interventions:
- Drug: AVB-S6-500
- Drug: Paclitaxel
- Drug: Carboplatin
- Procedure: Tissue from Diagnostic Laparoscopy
- Procedure: Tissue from Core biopsy
- Procedure: Interval Debulking
- Procedure: Peripheral blood
- Procedure: Ascites collection
|
Not Provided
|
|
Withdrawn
|
0
|
30
|
August 31, 2029
|
August 31, 2024 (Final data collection date for primary outcome measure)
|
Inclusion Criteria:
Exclusion Criteria:
|
Sexes Eligible for Study: |
Female |
|
18 Years and older (Adult, Older Adult)
|
No
|
Contact information is only displayed when the study is recruiting subjects
|
Not Provided
|
United States
|
|
NCT03607955
|
18-x211
|
Yes
|
Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
Product Manufactured in and Exported from the U.S.: |
No |
|
|
Washington University School of Medicine
|
Same as current
|
Washington University School of Medicine
|
Same as current
|
Aravive, Inc.
|
Principal Investigator: |
Katherine C Fuh, M.D., Ph.D. |
Washington University School of Medicine |
|
Washington University School of Medicine
|
September 2021
|