Clinical Trials /

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

NCT04004442

Description:

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.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Avelumab in Combination With AVB-S6-500 in Patients With Advanced Urothelial Carcinoma
  • Official Title: Phase II Study of Avelumab in Combination With AXL Inhibitor AVB-S6-500 in Patients With Advanced Urothelial Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: OU-SCC-COAXIN
  • NCT ID: NCT04004442

Conditions

  • Urothelial Carcinoma

Interventions

DrugSynonymsArms
AvelumabAvelumab + AVB-S6-500
AVB-S6-500Avelumab + AVB-S6-500

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Avelumab + AVB-S6-500Experimental
  • Avelumab
  • AVB-S6-500

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate
Time Frame:up to 2 years
Safety Issue:
Description:the proportion of partial and complete response in evaluable patients treated with combination therapy

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:up to two years
Safety Issue:
Description: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)
Measure:Clinical Benefit Rate
Time Frame:up to two years
Safety Issue:
Description:proportion of patients with complete or partial response, or stable disease per RECIST 1.1 on treatment with avelumab and ABV-S6-500
Measure:Duration of Response
Time Frame:up to two years
Safety Issue:
Description: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)
Measure:Overall Survival
Time Frame:up to two years
Safety Issue:
Description:the period from patient enrollment until death, or date of last contact or to the date of censoring (end of study)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Oklahoma

Trial Keywords

  • avelumab
  • AVB-S6-500
  • renal pelvis cancer
  • ureter cancer
  • urinary bladder cancer
  • urethra cancer

Last Updated

March 3, 2020