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Avelumab in Combination With AVB-S6-500 in Patients With Advanced Urothelial Carcinoma (COAXIN)

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. Identifier: NCT04004442
Recruitment Status : Recruiting
First Posted : July 2, 2019
Last Update Posted : June 16, 2020
Aravive, Inc.
EMD Serono
Information provided by (Responsible Party):
University of Oklahoma

Brief Summary:
The purpose of this research study is to test the safety of avelumab and AVB-S6-500 and see what effects (good and bad) this combination treatment has on patients with advanced urothelial carcinoma.

Condition or disease Intervention/treatment Phase
Urothelial Carcinoma Drug: Avelumab Drug: AVB-S6-500 Phase 2

Detailed Description:

Patients will have tests and exams to see if they are eligible for the clinical trial. If found eligible, the patient will receive treatment with avelumab and AVB-S6-500 by vein once every two weeks.

This study has two parts in order to determine the maximum tolerated dose of AVB-S6-500. If the patient is enrolled on the first dose level, the patient will be treated at a higher dose every two weeks with AVB-S6-500. If the patient is enrolled on the second dose level, the patient will be receive AVB-S6-500 only once a week at a lower dose. The patient would continue to receive avelumab twice weekly at the same dose.

Patients will receive the study treatment as long as there is evidence that the tumor is not growing or spreading and they are not having any unacceptable, bad side effects.

Patients will be monitored during treatment with tests and exams and after treatment completion for up to one year.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 31 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Avelumab in Combination With AXL Inhibitor AVB-S6-500 in Patients With Advanced Urothelial Carcinoma
Actual Study Start Date : February 17, 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Avelumab

Arm Intervention/treatment
Experimental: Avelumab + AVB-S6-500 Drug: Avelumab
Avelumab: 800 mg IV every two weeks (on days 1 and 15 of a 28-day cycle)

Drug: AVB-S6-500
AVB-S6-500: 10mg/kg IV every 2 weeks (on days 1 and 15 of a 28-day cycle) Potential dose reduction: AVB-S6-500: 5mg/kg IV weekly (on days 1, 8, 15 and 22 of a 28-day cycle)

Primary Outcome Measures :
  1. Objective Response Rate [ Time Frame: up to 2 years ]
    the proportion of partial and complete response in evaluable patients treated with combination therapy

  2. Incidence of Dose Limiting Toxicities [ Time Frame: 28 days ]

Secondary Outcome Measures :
  1. Progression Free Survival [ Time Frame: up to two years ]
    period from the time of patient enrollment until disease progression, death, or date of last contact or to the date of censoring (dropout, end of study or death)

  2. Clinical Benefit Rate [ Time Frame: up to two years ]
    proportion of patients with complete or partial response, or stable disease per RECIST 1.1 on treatment with avelumab and ABV-S6-500

  3. Duration of Response [ Time Frame: up to two years ]
    defined as the period from the date of confirmed tumor response until disease progression, death, or date of last contact or to the date of censoring (dropout, end of study or death)

  4. Overall Survival [ Time Frame: up to two years ]
    the period from patient enrollment until death, or date of last contact or to the date of censoring (end of study)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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

Inclusion Criteria:

  1. Age ≥18 years
  2. Histologically confirmed locally advanced unresectable (T4b or N2/N3 disease) or metastatic urothelial cancer (including renal pelvis, ureters, urinary bladder, urethra).
  3. Eligible patients must have had either:

    1. Progressed after treatment with at least 1 prior platinum-containing regimen, (e.g., received at least 2 cycles of cisplatin or carboplatin-based regimen) for inoperable locally advanced unresectable or metastatic urothelial carcinoma, OR
    2. Unable to tolerate platinum (cisplatin or carboplatin) based chemotherapy due to toxicity, OR
    3. Experienced disease progression or recurrence within 12 months of completion of neoadjuvant or adjuvant cisplatin-based chemotherapy, OR
    4. Ineligible for cisplatin-based chemotherapy due to eastern co-operative oncology group (ECOG) performance status 2, grade ≥2 neuropathy, GFR<60 mL/Hr, grade ≥2 hearing loss and New York Heart Association class III or worse congestive heart failure.
  4. Available pretreatment baseline tumor specimen or willingness to undergo biopsy of primary or metastatic lesion if archived specimen is not available.
  5. ECOG performance status of ≤2
  6. At least one measurable lesion by RECIST version 1.1
  7. Patients who are able to understand and sign the informed consent form.
  8. Ability to comply with protocol
  9. Adequate hematologic and end-organ function per protocol
  10. For women of childbearing potential: Negative serum or urine pregnancy test at screening.
  11. For both male and female subjects: agreement to remain abstinent (refrain from heterosexual intercourse) or use highly effective contraceptive methods that result in a failure rate of <1% per year during the treatment period and for at least 30 days after the last dose of study drug

Exclusion Criteria:

  1. Concurrent systemic treatment with an anticancer treatment or investigational drug within 28 days. Palliative radiation to symptomatic primary tumor or metastases is permitted as long as there are other measurable lesions present outside of the radiation field.
  2. Prior therapy with anti-PD-1 or PD-L1 agents.
  3. Concurrent systemic therapy with corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive agents within 28 days before starting trial drug. Short-term administration of systemic steroids (less than 7 days), adrenal replacement steroid doses (≤10 mg daily prednisone equivalent), topical, intranasal and inhaled steroid use is permitted.
  4. Patients with untreated or symptomatic central nervous metastases will be excluded. Appropriately treated CNS metastases with either surgery or radiation therapy are permitted to participate in the study.
  5. Active second malignancy or previous history of malignant disease (other than urothelial carcinoma) diagnosed within the last 3 years, with the exclusion of basal or squamous cell carcinoma of the skin, cervical carcinoma in situ and prostate adenocarcinoma with Gleason score ≤7, pT2b.
  6. Prior organ transplantation, including allogenic stem-cell transplantation.
  7. Known history of testing positive for HIV/AIDS, HBV, or HCV (including acute and chronic infection).
  8. Known hypersensitivity to monoclonal antibody or any biologic drug, history of anaphylaxis, or uncontrolled asthma.
  9. Persisting toxicity related to prior therapy that was > grade 1; grade ≤2 sensory neuropathy is allowed.
  10. Pregnant or lactating, or intending to become pregnant during the study

    a. Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative pregnancy test result within 14 days prior to the first dose of study treatment.

  11. Diagnosis of active autoimmune disease requiring systemic immunosuppression. Patients with type 1 diabetes, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring systemic immunosuppression are eligible.
  12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

    a. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.

  13. Active infection requiring systemic therapy.
  14. Severe infections within 4 weeks prior to the first dose of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  15. Administration of a live/attenuated vaccine within 4 weeks prior to the first dose of study treatment, within 5 months following the administration of the last dose of study drug, or anticipation that such a live/attenuated vaccine will be required during the study.
  16. Other severe acute or chronic medical conditions per protocol

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 identifier (NCT number): NCT04004442

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Contact: Lead GU Nurse 1-405-271-8777
Contact: Ingrid Block 1-405-271-8777

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United States, California
City of Hope National Medical Center Not yet recruiting
Duarte, California, United States, 91010
Contact: Yung Lyou, MD, PhD    626-218-9200   
Principal Investigator: Yung Lyou, MD, PhD         
United States, New Mexico
University of New Mexico Comprehensive Cancer Center Not yet recruiting
Albuquerque, New Mexico, United States, 87131
Contact: Neda Hashemi, MD, PhD    505-925-0391   
Principal Investigator: Neda Hashemi, MD, PhD         
United States, Oklahoma
Stephenson Cancer Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Lead GU Nurse   
Principal Investigator: Abhishek Tripathi, MD         
United States, Utah
Huntsman Cancer Institutes Not yet recruiting
Salt Lake City, Utah, United States, 84112
Contact: Sumati Gupta, MD    801-213-5727   
Principal Investigator: Sumati Gupta, MD         
Sponsors and Collaborators
University of Oklahoma
Aravive, Inc.
EMD Serono
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Principal Investigator: Abhishek Tripathi, MD Stephenson Cancer Center
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Responsible Party: University of Oklahoma Identifier: NCT04004442    
Other Study ID Numbers: OU-SCC-COAXIN
First Posted: July 2, 2019    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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 University of Oklahoma:
renal pelvis cancer
ureter cancer
urinary bladder cancer
urethra cancer
Additional relevant MeSH terms:
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Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type