AzTrials
AzTrials

Epithelial Ovarian CancerPhase 1NCT03607955

Paclitaxel + Carboplatin With AVB-S6-500 in Women With Stage III or IV Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Receiving Neoadjuvant Chemotherapy

A Phase 1 study testing AVB-S6-500, Paclitaxel and Carboplatin in people with Epithelial Ovarian Cancer and Primary Peritoneal Carcinoma, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial 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]}. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
AVB-S6-500, Paclitaxel and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Jun 2021to 31 Aug 2029
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 24Show fewer
  • 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).

Who cannot join

  • 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.
Show all 21Show fewer
  • 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.

About this study

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

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.

Being tested
AVB-S6-500, Paclitaxel, Carboplatin, Tissue from Diagnostic Laparoscopy, Tissue from Core biopsy
Medical subject headings
Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AVB-S6-500Drug

    AVB-S6-500 is supplied by Aravive Biologics

  • PaclitaxelDrug

    Also called Taxol

    Commercially available

  • CarboplatinDrug

    Also called Paraplatin

    Commercially available

  • Tissue from Diagnostic LaparoscopyProcedure or surgery

    -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

  • Tissue from Core biopsyProcedure or surgery

    -Standard of care procedure but research specimens will be collected

  • Interval DebulkingProcedure or surgery

    • Standard of Care
    • Research tissue samples will be collected

  • Peripheral bloodProcedure or surgery

    -Before initiation of neoadjuvant chemotherapy and at the time of interval debulking surgery either pre-operatively, intraoperatively, or post-operatively.

  • Ascites collectionProcedure or surgery

    -A total of 25-100ml of ascites will be collected prior to chemotherapy treatment, if available.

Study groups in NCT03607955
Study groupRoleWhat they receive
AVB-S6-500 + Paclitaxel + CarboplatinExperimental* 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).
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum tolerated dose (MTD) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    • 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.

    Measured: Completion of the enrollment and treatment of all patients (estimated to be approximately 26 months)

  2. Dose limiting toxicities (DLTs) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    -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)

    Measured: Through completion of 1st cycle for all patients (estimated to be 13 months)

  3. Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by treatment discontinuation

    Measured: Through completion of treatment (estimated to be 14 months)

  4. 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

    Measured: Through completion of treatment (estimated to be 14 months)

  5. 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

    Measured: Through completion of treatment (estimated to be 14 months)

  6. 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

    Measured: Through completion of treatment (estimated to be 14 months)

  7. Tolerability of the combination at the MTD of AVB-S6-500 assessed in combination with standard neoadjuvant chemotherapy as measured by number of deaths

    Measured: Through completion of treatment (estimated to be 14 months)

Secondary outcomes (5)

  1. Objective clinical response (cOR) of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    -cOR = clinical response seen at the time of surgery with no visible disease

    Measured: At the time of interval debulking (approximately 9-12 weeks)

  2. Pathological complete response (pCR) at the time of interval debulking surgery of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    -pCR = pathological response seen by the pathology at the time of surgery with treatment effect and no disease seen microscopically

    Measured: At the time of interval debulking (approximately 9-12 weeks)

  3. Progression-free survival (PFS) at 1 year after debulking surgery of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    • 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).

    Measured: 1 year after debulking surgery (approximately 64 weeks)

  4. Progression-free survival (PFS) at 2 years after debulking surgery of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    • 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).

    Measured: 2 years after debulking surgery (approximately 116 weeks)

  5. Overall survival (OS) by long-term follow-up of AVB-S6-500 in combination with and following conventional chemotherapy and maintenance

    -OS is defined as the time from the date of treatment to the date of death, censored at the last follow-up otherwise.

    Measured: 5 years after completion of treatment (approximately 74 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2018
  2. Study start30 Jun 2021 (estimated)
  3. Primary completion31 Aug 2024 (estimated)
  4. Study completion31 Aug 2029 (estimated)

Why it stopped: Trial may move forward as an NCI-sponsored trial and not an investigator initiated trial.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03607955
Sponsor's protocol ID
18-x211
Status last verified
Sep 2021
First submitted
23 Jul 2018
Last updated
29 Sep 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AVB-S6-500, Paclitaxel and Carboplatin in people with Epithelial Ovarian Cancer and Primary Peritoneal Carcinoma, run by Washington University School of Medicine.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the 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 lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03607955.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2021.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in