Clinical Trials /

Cabometyx and Avelumab in Patients With Metastatic Renal Cell Carcinoma (mRCC)

NCT03200587

Description:

This is an open-label, non-controlled, non-randomized, phase I dose-finding, of Cabometyx + Avelumab, to establish safety, feasibility, and the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of Cabometyx in combination with Avelumab, and to investigate preliminary efficacy. The MTD or RP2D determined in this study will be used for a future study to formally test efficacy. The MTD determined by dose escalation will be the recommended Phase 2 dose.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Cabometyx and Avelumab in Patients With Metastatic Renal Cell Carcinoma (mRCC)
  • Official Title: A Phase 1B, Open Label, Dose-finding Study to Evaluate the Safety and Tolerability of Cabometyx and Avelumab in Patients With Metastatic Renal Cell Carcinoma (mRCC)

Clinical Trial IDs

  • ORG STUDY ID: HCI102309
  • NCT ID: NCT03200587

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
AvelumabAvelumab and cabozantinib, all patients
CabozantinibCabometyxAvelumab and cabozantinib, all patients

Purpose

This is an open-label, non-controlled, non-randomized, phase I dose-finding, of Cabometyx + Avelumab, to establish safety, feasibility, and the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of Cabometyx in combination with Avelumab, and to investigate preliminary efficacy. The MTD or RP2D determined in this study will be used for a future study to formally test efficacy.

Trial Arms

NameTypeDescriptionInterventions
Avelumab and cabozantinib, all patientsExperimental
  • Avelumab
  • Cabozantinib

Eligibility Criteria

        Inclusion Criteria:

        Pre-Screening Eligibility for Patients Scheduled for Cytoreductive Nephrectomy

          -  Male or female subject aged ≥ 18 years.

          -  Clinically, subject is a candidate for RCC diagnostic procedure (biopsy or surgery).

          -  Subject meets standard of care eligibility criteria for consideration of treatment
             with immunotherapy using a checkpoint inhibitor following surgical resection.

        Treatment Inclusion

          -  Male or female subject aged ≥ 18 years.

          -  Histologically proven mRCC with a clear cell component.

          -  Radiographic evidence of metastatic disease.

          -  Measureable disease by RECIST 1.1

          -  ECOG Score 0-1

          -  Adequate organ function as described in the protocol

          -  Negative serum or urine pregnancy test at screening for women of childbearing
             potential

          -  Highly effective contraception for both male and female subjects throughout the study
             and for at least 120 days after last Avelumab treatment administration if the risk of
             conception exists

          -  Able to provide informed consent and willing to sign an approved consent form that
             conforms to federal and institutional guidelines.

        Exclusion Criteria:

          -  Current use of immunosuppressive medication, EXCEPT for the following:

               1. intranasal, inhaled, topical steroids, or local steroid injection (e.g.,
                  intra-articular injection);

               2. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or
                  equivalent;

               3. Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication).

          -  Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory
             agent per treating physician's clinical judgment. Subjects with diabetes type I,
             vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive
             treatment are eligible.

          -  Prior organ transplantation including allogenic stem-cell transplantation.

          -  Active infection requiring intravenous antibiotics (antibiotics should have been
             completed prior to registration).

          -  Known history of testing positive for HIV or known acquired immunodeficiency syndrome.

          -  Known history of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at
             screening (positive HBV surface antigen or detectable HCV RNA if anti-HCV antibody
             screening test positive)

          -  Active and inactive vaccinations within 4 weeks of the first dose of Avelumab and
             while on trial is prohibited.

          -  Known prior severe hypersensitivity to investigational product or any component in its
             formulations, including known severe hypersensitivity reactions to monoclonal
             antibodies (NCI CTCAE v4.03 Grade ≥ 3).

          -  Clinically significant (i.e., active) cardiovascular disease: cerebral vascular
             accident/stroke (< 6 months prior to enrollment), myocardial infarction (< 6 months
             prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart
             Association Classification Class II), or serious cardiac arrhythmia requiring
             medication.

          -  Persisting toxicity related to prior therapy (NCI CTCAE v. 4.03 Grade > 1); however,
             alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety
             risk based on investigator's judgment are acceptable.

          -  Other severe acute or chronic medical conditions including colitis, inflammatory bowel
             disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent
             (within the past year) or active suicidal ideation or behavior; or laboratory
             abnormalities that may increase the risk associated with study participation or study
             treatment administration or may interfere with the interpretation of study results
             and, in the judgment of the investigator, would make the patient inappropriate for
             entry into this study.

          -  Subjects taking prohibited medications as described in protocol. A washout period of
             prohibited medications for a period of at least two weeks or as clinically indicated
             should occur prior to the start of treatment

          -  Pregnant women or lactating women who are breastfeeding are excluded from this study.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Determine the recommended Phase II dose
Time Frame:1 cycle (28 days)
Safety Issue:
Description:To assess the safety and tolerability of Avelumab + Cabometyx in subjects with mRCC and determine the recommended Phase II dose (RP2D). Safety, tolerability, adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs).

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:2 years (Most patients are expected to be on treatment for approximately 10 months)
Safety Issue:
Description:To evaluate the clinical activity of Avelumab + Cabometyx in subjects with mRCC

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

Trial Keywords

  • Metastatic

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