Brief Title
Paclitaxel + Carboplatin With AVB-S6-500 in Women With Stage III or IV Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Receiving Neoadjuvant Chemotherapy
Official Title
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
Brief Summary
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Maximum tolerated dose (MTD) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance
Secondary Outcome
Objective clinical response (cOR) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance
Condition
Epithelial Ovarian Cancer
Intervention
AVB-S6-500
Study Arms / Comparison Groups
AVB-S6-500 + Paclitaxel + Carboplatin
Description: 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).
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
30
Start Date
December 31, 2020
Completion Date
February 28, 2028
Primary Completion Date
February 28, 2023
Eligibility Criteria
Inclusion Criteria:
- Histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal
cancer per pre-treatment biopsies by laparoscopy or interventional radiology or
CT-guided core biopsy.
- Patients with the following histologic epithelial cell types are eligible:
- High grade serous adenocarcinoma
- Endometrioid adenocarcinoma
- Undifferentiated carcinoma
- Clear cell adenocarcinoma
- Mixed epithelia carcinoma
- Adenocarcinoma not otherwise specified (NOS)
- Disease must be considered "bulky" by the clinician (unresectable via primary
debulking surgery) and in need of neoadjuvant chemotherapy prior to debulking surgery.
This assessment of unresectability can be made via imaging or laparoscopic scoring.
- Must have pre-treatment tumor tissue available or agree to tissue collection from
IR-guided biopsy.
- Any hormonal therapy directed at the malignant tumor must be discontinued at least one
week prior to registration. Continuation of hormone replacement therapy is permitted.
- At least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Normal bone marrow and organ function as defined below:
- Absolute neutrophil count ≥ 1,500/mcl
- Platelets ≥ 100,000/mcl
- Hemoglobin ≥ 9.0 g/dL
- Total bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (unless liver metastases are present in which
case AST/ALT must be ≤ 5.0 x IULN)
- Serum creatinine < 2.0 mg/dL or < 177 µmol/L OR calculated or measured creatinine
clearance ≥ 40 mL/min (using Cockcroft-Gault equation)
- INR ≤ 1.5 x IULN
- aPTT ≤ 1.5 x IULN
- Women of childbearing potential must agree to use adequate contraception (hormonal or
barrier method of birth control, abstinence) prior to study entry and for the duration
of study participation. Should a woman become pregnant or suspect she is pregnant
while participating in this study, she must inform her treating physician immediately.
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
Exclusion Criteria:
- Any prior treatment with AVB-S6-500 or standard of care drugs (cisplatin, carboplatin,
paclitaxel).
- A history of other malignancy ≤ 3 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only.
Patients with concomitant endometrial cancer diagnosed at the time of the ovarian
cancer are allowed to participate if the endometrial cancer is FIGO stage IB or less.
- Currently receiving any other (non-study) cytotoxic chemotherapy.
- Currently receiving any other investigational agents or has received an
investigational agent within 4 weeks of start of study treatment.
- Known brain metastases. Patients with known brain metastases must be excluded from
this clinical trial because of their poor prognosis and because they often develop
progressive neurologic dysfunction that would confound the evaluation of neurologic
and other adverse events.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to AVB-S6-500 or other agents used in the study.
- Abnormal gastrointestinal function (nausea or vomiting). This includes GI obstruction
or bleeding or signs/symptoms thereof within 3 months of study enrollment. Patients
with a history of abdominal fistula will be considered eligible if the fistula was
surgically repaired or has healed, there has been no evidence of fistula for at least
6 months, and patient is deemed to be at low risk of recurrent fistula.
- Significant cardiac disease history including:
- Clinically significant atrial or ventricular arrhythmias requiring treatment
- Medically controlled congestive heart failure
- Significant angina or clinically and/or electrocardiographically documented
myocardial infarction within the past year
- Clinically significant valvular disease
- Non-healing wound, ulcer, or bone fracture.
- Receiving treatment for active autoimmune disease. "Active" refers to any condition
currently requiring therapy.
- Received prior radiotherapy to any portion of the abdominal cavity or pelvis. Prior
radiation for localized cancer of the breast, head and neck, or skin is permitted,
provided that it was completed more than 3 years prior to registration and the patient
remains free of recurrent or metastatic disease.
- Received prior chemotherapy for any abdominal or pelvic tumor. Prior adjuvant
chemotherapy for localized breast cancer is permitted, provided that was completed
more than 3 years prior to registration and the patient remains free of recurrent or
metastatic disease.
- Known active hepatitis; ongoing systemic bacterial, fungal, or viral infection; known
HIV infection or AIDS-related illness.
- History or evidence upon physical examination of CNS disease, including primary brain
tumor, seizures not controlled with standard medical therapy, or history of CVA, TIA,
or subarachnoid hemorrhage within 6 months of the first date of treatment on this
study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac
arrhythmia.
- History of major surgical procedure within 21 days prior to start of study treatment.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 14 days of study entry.
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Katherine C Fuh, M.D., Ph.D., 314-362-8155, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT03607955
Organization ID
18-x211
Responsible Party
Sponsor
Study Sponsor
Washington University School of Medicine
Collaborators
Aravive, Inc.
Study Sponsor
Katherine C Fuh, M.D., Ph.D., Principal Investigator, Washington University School of Medicine
Verification Date
July 2020