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

• ClinicalTrials.gov Identifier: NCT03200587
• Recruitment Status: Completed
• First Posted: June 27, 2017
• Last Update Posted: May 6, 2022
• Sponsor: University of Utah
• Collaborator: EMD Serono
• Information provided by (Responsible Party): University of Utah

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Renal Cell Carcinoma	Drug: Avelumab; Drug: Cabozantinib	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: A phase 1B, open label, dose-finding study
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: June 21, 2018
• Actual Primary Completion Date: April 14, 2020
• Actual Study Completion Date: November 25, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Avelumab and cabozantinib, all patients	Drug: Avelumab; Avelumab 10 mg/kg infusion every 2 weeks (Days 1 and 15) of every 28 day cycle for up to 12 cycles; Drug: Cabozantinib; Cabozantinib oral daily at 20 (starting dose 1), 40 (Dose Level 2) or 60 mg (Dose Level 3); Other Name: Cabometyx

Outcome Measures

Primary Outcome Measures :

1. Determine the recommended Phase II dose [ Time Frame: 1 cycle (28 days) ]
   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 :

1. Progression Free Survival (PFS) [ Time Frame: 2 years (Most patients are expected to be on treatment for approximately 10 months) ]
   To describe the clinical activity of Avelumab + Cabometyx in subjects with mRCC

Eligibility Criteria

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

Criteria

Inclusion Criteria:

Optional 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 or biopsy.

Treatment Inclusion

• Male or female subject aged ≥ 18 years.
• Histologically proven renal cell carcinoma with a clear cell component.
• Radiographic evidence of metastatic disease.
• Measureable disease by RECIST 1.1
• ECOG Score 0-2
• 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 active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. If the patient has a history of HBV or HCV then confirmatory PCR testing is required to confirm the disease is not active.
• Live vaccinations within 4 weeks of the first dose of Avelumab and while on trial is prohibited.
• Piror exposure to checkpoint therapy or Cabozantinib.
• 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.
• Stroke (including transient ischemic attack (TIA), myocardial infarction, or other ischemic event or symptomatic pulmonary embolism (PE) less than or equal to 6 months before dose of Cabometyx.
• Subjects with a diagnosis of deep vein thrombosis (DVT) or incidentally detected asymptomatic PE on routine scans are allowed if stable and treated with therapeutic anticoagulation for at least 2 weeks before first dose.
• Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 12 weeks before first dose.

Contacts and Locations

Locations

United States, Utah

Huntsman Cancer Institute

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

University of Utah

EMD Serono

Investigators

• Principal Investigator: Neeraj Agarwal, MD; Huntsman Cancer Institute

More Information

• Responsible Party: University of Utah
• ClinicalTrials.gov Identifier: NCT03200587
• Other Study ID Numbers: HCI102309
• First Posted: June 27, 2017
• Last Update Posted: May 6, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Utah:

Metastatic

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Renal Cell; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Avelumab; Antineoplastic Agents, Immunological; Antineoplastic Agents