Rapid Sequencing of Approved Therapies in Patients with Metastatic or Unresectable Clear Cell Renal Cell Carcinoma

NCT05188118 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: GCO 21-1913
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot, single-center, single-arm study where 20 patients with metastatic or unresectable clear cell renal cell carcinoma will receive same sequential treatment strategy (Cabozantinib for 12 weeks, then proceed with Ipilimumab plus Nivolumab immunotherapy x4 over 12 weeks, then subsequent therapies depending on treatment response for another 12 weeks \[Nivolumab for CR/PR/SD, Cabozantinib or Lenvatinib/Everolimus for PROG\]).

Conditions

Renal Cell Carcinoma

Keywords

Clear cell; Renal cell carcinoma; Metastatic; Unresectable; Immunotherapy; Targeted therapy

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate (ORR)

  ORR is defined as the proportion of subjects who achieved a best response of CR or PR using the RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum longest diameters

  9 months

Secondary Outcomes (4)

• Diagnostic Odds Ratio (DoR)

  9 months

• Progression-Free Survival (PFS)

  9 months

• Overall Survival (OS)

  9 months

• Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19)

  9 months

Study Arms (1)

Patients with metastatic or unresectable clear cell renal cell carcinoma

EXPERIMENTAL

Patients with metastatic or unresectable clear cell renal cell carcinoma to receive same sequential treatment strategy. (Cabozantinib for 12 weeks, then proceed with Ipilimumab plus Nivolumab immunotherapy x4 over 12 weeks, then subsequent therapies depending on treatment response for another 12 weeks \[Nivolumab for CR/PR/SD, Cabozantinib or Lenvatinib/Everolimus for PROG\]).

Drug: Cabozantinib; Drug: Ipilimumab; Drug: Nivolumab; Drug: Lenvatinib; Drug: Everolimus

Interventions

Cabozantinib DRUG

60mg oral once daily for 12 weeks

Patients with metastatic or unresectable clear cell renal cell carcinoma

Ipilimumab DRUG

1mg/kg intravenous once every 3 weeks over 12 weeks

Patients with metastatic or unresectable clear cell renal cell carcinoma

Nivolumab DRUG

3mg/kg intravenous once every 3 weeks over 12 weeks, then 480mg once every 4 weeks after

Patients with metastatic or unresectable clear cell renal cell carcinoma

Lenvatinib DRUG

18mg oral once daily for 12 weeks

Patients with metastatic or unresectable clear cell renal cell carcinoma

Everolimus DRUG

5mg oral once daily for 12 weeks

Patients with metastatic or unresectable clear cell renal cell carcinoma

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years at the time of study entry
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• ECOG performance status of 0 or 1 or KPS of at least 80%
• Life expectancy ≥ 12 weeks
• Histologically confirmed advanced (not amenable to curative surgery or radiation therapy) or metastatic (stage IV) RCC with predominantly clear cell component (sarcomatoid differentiation \<50%)
• a. Patients with localized RCC who develop metastatic disease post definitive nephrectomy, with or without systemic therapy in the adjuvant setting, are eligible
• Patients with favorable, intermediate, or poor risk categories as defined by the MSKCC Prognostic Model or the IMDC consortium (Appendix A) will be eligible for the study
• Evidence of measurable disease per RECIST 1.1 (i.e., ≥1 malignant tumor mass ≥10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm)
• Adequate normal organ, marrow and coagulation function based on below labs within 14 days before first dose of study treatment:
• Hgb ≥ 9.0g/dL
• White blood count ≥ 2500/ µL
• ANC ≥1 x 109/L (≥1500/L) without growth factor support
• Plt count ≥ 100 x 109 /L (≥100,000/L) without transfusion
• Total serum bilirubin ≤1.5 x institutional ULN; Gilbert's disease, Total serum bilirubin ≤3 x institutional ULN
• Serum transaminases (AST/ALT) ≤3 x the institutional ULN; ALP ≤5 x the institutional ULN with documented bone metastasis

You may not qualify if:

• Prior treatment with cabozantinib, nivolumab, ipilimumab, or any other systemic kidney cancer directed therapy for advanced disease (i.e. must be treatment naïve for advanced disease; adjuvant treatment post definitive local therapy is acceptable).
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) within 4 weeks or five half-lives of the anti-cancer therapy prior to the first dose of study drug, whichever is shorter.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Radiation therapy for bone metastases within 2 weeks, any other radiation therapy within 4 weeks, or systemic treatment with radionuclides within 6 weeks before first dose of study treatment; ongoing clinically relevant complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks prior to first dose of study treatment.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or platelet inhibitors (e.g., clopidogrel). Allowed anticoagulants are the following:
• Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins.
• Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has uncontrolled, significant inter-current or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• I. Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias.
• II. Uncontrolled hypertension defined as sustained blood pressure \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.
• III. Stroke (including TIA), MI, or other ischemic event, or thromboembolic event (e.g., DVT, PE) within 6 months before first dose of study treatment.
• GI disorders including those associated with a high risk of perforation or fistula formation:
• I. The subject has evidence of tumor invading the GI tract, active peptic ulcer disease, inflammatory bowel disease (e.g., Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis, acute obstruction of the pancreatic duct or common bile duct, or gastric outlet obstruction.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell; Neoplasm Metastasis

Interventions

cabozantinib; Ipilimumab; Nivolumab; lenvatinib; Everolimus

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Che-Kai Tsao

  Investigator

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Che-Kai Tsao, MD

CONTACT

212-824-8782; che-kai.tsao@mssm.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 27, 2021
• First Posted: January 12, 2022
• Study Start: February 15, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 6, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Anyone who wishes to access the data. Any purpose. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.

Locations

US (1)