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Efficacy and Safety Study of AVB-S6-500 in Patients With Platinum-Resistant Recurrent Ovarian Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03639246
Recruitment Status : Recruiting
First Posted : August 21, 2018
Last Update Posted : November 6, 2019
Sponsor:
Information provided by (Responsible Party):
Aravive, Inc.

Brief Summary:
This is a Phase 1b/2 study of AVB-S6-500 in combination with pegylated liposomal doxorubicin (PLD) or paclitaxel (Pac) in patients with platinum resistant recurrent ovarian cancer. The phase 1b portion of the study is open label and patients will receive either AVB-S6-500+PLD or AVB-S6-500+ Pac. The Phase 2 portion of the study is randomized, double-blind, placebo-controlled study to compare efficacy and tolerability of AVB-S6-500 in combination with PLD or Pac versus placebo plus PLD or Pac.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: AVB-S6-500 Drug: Paclitaxel (Pac) Drug: Pegylated liposomal doxorubicin (PLD) Other: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 196 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1b/2 Randomized, Controlled Study of AVB-S6-500 in Combination With Pegylated Liposomal Doxorubicin (PLD) or Paclitaxel (Pac) in Patients With Platinum-resistant Recurrent Ovarian Cancer
Actual Study Start Date : December 3, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022


Arm Intervention/treatment
Experimental: Phase 1b: AVB-S6-500+PLD Drug: AVB-S6-500
AVB-S6-500 is experimental drug

Drug: Pegylated liposomal doxorubicin (PLD)
PLD is active comparator
Other Name: Doxil

Experimental: Phase 1b: AVB-S6-500+Pac Drug: AVB-S6-500
AVB-S6-500 is experimental drug

Drug: Paclitaxel (Pac)
Paclitaxel is active comparator
Other Name: Taxol

Experimental: Phase 2: AVB-S6-500+PLD Drug: AVB-S6-500
AVB-S6-500 is experimental drug

Drug: Pegylated liposomal doxorubicin (PLD)
PLD is active comparator
Other Name: Doxil

Experimental: Phase 2: AVB-S6-500+Pac Drug: AVB-S6-500
AVB-S6-500 is experimental drug

Drug: Paclitaxel (Pac)
Paclitaxel is active comparator
Other Name: Taxol

Active Comparator: Phase 2: Placebo+PLD Drug: Pegylated liposomal doxorubicin (PLD)
PLD is active comparator
Other Name: Doxil

Other: Placebo
Placebo comparator

Active Comparator: Phase 2: Placebo+Pac Drug: Paclitaxel (Pac)
Paclitaxel is active comparator
Other Name: Taxol

Other: Placebo
Placebo comparator




Primary Outcome Measures :
  1. Incidence of Adverse Events (AEs) [ Time Frame: 6 months ]
    Measured by the number of patients with AEs in Phase 1 portion of the study.

  2. Anti-tumor activity of AVB-S6-500 in combination with PLD [ Time Frame: 18 months ]
    Measured by progression free survival (PFS) in patients receiving AVB-S6-500+PLD versus patients receiving Placebo+PLD in Phase 2 portion of the study.

  3. Anti-tumor activity of AVB-S6-500 in combination with Pac [ Time Frame: 18 months ]
    Measured by progression free survival (PFS) in patients receiving AVB-S6-500+ Pac versus patients receiving Placebo+Pac in Phase 2 portion of the study.


Secondary Outcome Measures :
  1. Pharmacokinetics: AUC [ Time Frame: 18 months ]
    Area under the AVB-S6-500 concentration-time curve.

  2. Pharmacokinetics: Cmax [ Time Frame: 18 months ]
    Maximum observed AVB-S6-500 concentration.

  3. Pharmacokinetics: Tmax [ Time Frame: 18 months ]
    Time of maximum observed AVB-S6-500 concentration.

  4. Pharmacokinetics: t1/2 [ Time Frame: 18 months ]
    Apparent terminal half-life of AVB-S6-500.

  5. Pharmacodynamic marker assessment [ Time Frame: 18 months ]
    Change from the baseline in GAS6 serum levels.

  6. Anti-drug antibody (ADA) titers [ Time Frame: 18 months ]
    Change from baseline in ADA titer.

  7. Objective response rate [ Time Frame: 18 months ]
    Proportion of subjects who have a partial or complete response to therapy relative to baseline as assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as well as Gynecologic Cancer Intergroup (GCIG) cancer antigen (CA)-125 criteria.

  8. Disease control rate [ Time Frame: 18 months ]
    Proportion of subjects who have a complete or partial response to therapy or maintain stable disease.

  9. Duration of response (DOR) [ Time Frame: 18 months ]
    Measured from the date of partial or complete response to therapy until the cancer progresses.

  10. Overall survival [ Time Frame: 30 months ]
    Time following the treatment until death.

  11. CA-125 response rate [ Time Frame: 18 months ]
    Proportion of subjects with a minimum 50% reduction in CA-125 serum levels lasting for 28 days relative to baseline CA-125 serum levels.

  12. Quality of Life(QOL) [ Time Frame: 18 months ]
    Subject QOL will be assessed every 8 weeks during treatment using the Functional Assessment Of Cancer Therapy - Ovarian Cancer (FACT-O) questionnaire, which consists of 4 subscales: physical well-being (7 questions), social/family well-being (7 questions), emotional well-being (6 questions), and functional well-being (7 questions), and 12 additional concerns specific to ovarian cancer. All items are rated on a 5 point scale with 0 "not at all" and 4 "very much". The scoring algorithm allows for eight summary scales: the four core well-being subscales, a subtotal of the 27 core items, a subtotal of the 12 ovarian-specific additional concerns, a grand total of the 39 items, and a trial outcome index (sum of the 17 physical and functional wellbeing items plus the 12 ovarian-specific items).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 years or older
  • Histologically confirmed and documented recurrent ovarian, fallopian tube, and peritoneal cancer.
  • Platinum resistant disease, defined as progression within ≤ 6 months from completion of most recent regimen and calculated from the date of the last administered dose of platinum therapy
  • Must have available archived tumor tissue OR if archived tissue is not available, willing to provide a fresh tumor biopsy
  • Must have radiologic imaging with a computerized tomography (CT) scan or magnetic resonance imaging (MRI) within 4 weeks of first dose of study drug
  • Received at least 1 but not more than 3 therapy regimens, not including maintenance or adjuvant therapy
  • Must have ovarian cancer that is measurable according to RECIST 1.1
  • ECOG performance status of 0-1
  • Normal gastrointestinal (GI), bone marrow, liver and kidney function
  • At least 28 days between termination of prior anti-cancer or hormonal therapy and administration of AVB-S6-500

Exclusion Criteria:

  • Primary platinum-refractory disease (defined as progression during the first platinum regimen or within 4 weeks of completion of the first platinum regimen)
  • Currently being treated with concurrent anti-cancer therapy or any other interventional treatment or trial
  • Received prior therapy with Pac or PLD in the recurrent setting, depending on physician-chosen chemotherapy for this study
  • Significant cardiac disease history
  • Has other prior or concurrent malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • Symptomatic CNS metastasis or metastases
  • Serious active infection requiring IV antibiotics and/or hospitalization at study entry
  • Has known previous or current human immune deficiency (HIV) syndrome, hepatitis B, or hepatitis C
  • Has had paracentesis for ascites within 3 months

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03639246


Contacts
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Contact: Aravive Clinical Trials 281-810-6749 clinicaltrials@aravive.com

Locations
Show Show 23 study locations
Sponsors and Collaborators
Aravive, Inc.
Investigators
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Study Director: Laura Bonifacio, PharmD, PhD Aravive Biologics Inc

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Responsible Party: Aravive, Inc.
ClinicalTrials.gov Identifier: NCT03639246    
Other Study ID Numbers: AVB500-OC-002
First Posted: August 21, 2018    Key Record Dates
Last Update Posted: November 6, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aravive, Inc.:
Ovarian cancer
Platinum resistant
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Paclitaxel
Albumin-Bound Paclitaxel
Doxorubicin
Liposomal doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors