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

NCT03200587 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: HCI102309
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Cell Carcinoma

Keywords

Metastatic

Outcome Measures

Primary Outcomes (1)

• Determine the recommended Phase II dose

  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).

  1 cycle (28 days)

Secondary Outcomes (1)

• Progression Free Survival (PFS)

  2 years (Most patients are expected to be on treatment for approximately 10 months)

Study Arms (1)

Avelumab and cabozantinib, all patients

EXPERIMENTAL

Drug: Avelumab; Drug: Cabozantinib

Interventions

Avelumab DRUG

Avelumab 10 mg/kg infusion every 2 weeks (Days 1 and 15) of every 28 day cycle for up to 12 cycles

Avelumab and cabozantinib, all patients

Cabozantinib DRUG

Cabozantinib oral daily at 20 (starting dose 1), 40 (Dose Level 2) or 60 mg (Dose Level 3)

Also known as: Cabometyx

Avelumab and cabozantinib, all patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female subject aged ≥ 18 years.
• Histologically proven renal cell carcinoma with a clear cell component.
• Radiographic evidence of metastatic disease.
• Measurable disease by RECIST 1.1
• Eastern Cooperative Oncology Group (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.

You may not qualify if:

• Current use of immunosuppressive medication, EXCEPT for the following:
• intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection);
• Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent;
• 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 polymerase chain reaction (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.
• Prior 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.

Sponsors & Collaborators

• University of Utah: lead
• EMD Serono: collaborator

Study Sites (1)

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Li H, Sahu KK, Brundage J, Benson M, Swami U, Boucher KM, Gupta S, Hawks J, Sirohi D, Agarwal N, Maughan BL. Phase I Trial of Combination Therapy With Avelumab and Cabozantinib in Patients With Newly Diagnosed Metastatic Clear Cell Renal Cell Carcinoma. Oncologist. 2023 Aug 3;28(8):737-e693. doi: 10.1093/oncolo/oyad019.

  PMID: 36952231 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

avelumab; cabozantinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; 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; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Neeraj Agarwal, MD

  Huntsman Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A phase 1B, open label, dose-finding study

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: June 27, 2017
• Study Start: June 21, 2018
• Primary Completion: April 14, 2020
• Study Completion: November 25, 2021
• Last Updated: July 3, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)