Cabozantinib as Subsequent Therapy to an Immune Checkpoint Based Therapy in Renal Cell Carcinoma

NCT04714697 | Unknown Phase 2

• 1 other identifier: AT ASIA
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase 2, multicenter, interventional for cohort 1 \& 2, non-interventional for cohort 3, open-label trial of cabozantinib, with ORR as the primary efficacy endpoint. In total, 201 eligible subjects will enroll from 5 sites in Korea. The intervention for this cohort 1\&2 is only IMP, Cabometyx provided by Ipsen (off-label). Also, cohort 3 is just RWD without IMP (on-label)

Conditions

Renal Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Objective response rate , per RECIST 1.1, per investigator assessment

  up to 2years

Secondary Outcomes (5)

• Time to response,

  up to 2years

• Duration of response

  up to 2years

• Progression-free survival

  up to 2years

• Overall survival

  up to 5years

• Incidence of Treatment Adverse Events incidence of treatment Adverse Events (safety)

  From date of Cycle 1Day 1 (first dosing) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24months

Study Arms (3)

Cohort 1(post nivolumab and ipilimumab combination)

EXPERIMENTAL

the subject who failed one prior line by nivolumab and ipilimumab

Drug: Cabometyx

Cohort 2 (post pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, or avelumab and axitinib)

EXPERIMENTAL

the subject who failed one prior line by PD-1/PD-L1 inhibitors in combination with VEGF TKI

Drug: Cabometyx

Cohort 3 (post sequential immunotherapy after VEGFR TKI)

NO INTERVENTION

the subject who failed the second line by immunotherapy (PD-1 antibody or PD-L1 antibody) following the first line VEGFR TKI

Interventions

Cabometyx DRUG

Cabometyx 60mg once daily, oral , up to Progression disease

Cohort 1(post nivolumab and ipilimumab combination); Cohort 2 (post pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, or avelumab and axitinib)

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented histological or cytological diagnosis of advanced renal cell cancer with or without clear-cell component with an exception of collecting duct carcinoma
• Measurable disease per RECIST 1.1, as determined by the investigator.
• Recovery to baseline or/and under Grade 1 CTCAE v.5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Age eighteen years or older on the day of consent.
• Karnofsky Performance Status (KPS) score of or/and over 70%.
• Adequate organ and marrow function, based upon meeting all of the following laboratory criteria within ten days before randomization:
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom).
• Female subjects of childbearing potential must not be pregnant at the screening. Females of childbearing potential are defined as premenopausal females capable of becoming pregnant (i.e., females who have had any evidence of menses in the past 12 months, except for those who had a prior hysterectomy). However, women who have been amenorrheic for 12 or more months are still considered childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, low body weight,ovarian suppression, or other reasons.
• Cohort-Specific Criteria Cohort 1
• Must have received nivolumab and ipilimumab combination as the first-line systemic treatment
• Subjects who experienced disease progression on nivolumab and ipilimumab combination or unacceptable toxicities.
• Cohort 2
• Must have received pembrolizumab plus axitinib, pembrolizumab plus Lenvatinib, or avelumab plus axitinib combination as the first-line systemic treatment
• Subjects who experienced disease progression on PD-1/PD-L1 inhibitors with VEGFR TKI combination or unacceptable toxicities.

You may not qualify if:

• Prior treatment with cabozantinib.
• Treated with any other investigational medicinal product (IMP) within the last 30 days before screening
• For cohort 1 \& 2, concurrent involvement participation in any investigational study.
• For cohort 3, participation in cabozantinib rPMS during the study
• Radiation therapy for bone metastasis within one week, any other external radiation therapy within two weeks before randomization. Subjects with clinically relevant ongoing 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 one month before randomization. Eligible subjects must be neurologically asymptomatic at the time of enrollment.
• Concomitant anticoagulation at therapeutic doses with oral anticoagulants (e.g., warfarin, direct thrombin, and Factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel).
• Note: Low-dose aspirin for cardioprotection (per locally applicable guidelines), low-dose warfarin (under 1 mg/day), and low dose, low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects without radiographic evidence of brain metastasis, who are on a stable dose of LMWH for at least 12 weeks before randomization, and who have had no complications from a thromboembolic event or the anticoagulation regimen.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Cardiovascular disorders:
• Symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias.
• Uncontrolled hypertension defined as sustained BP above 150 mm Hg systolic or 100 mm Hg diastolic despite optimal antihypertensive treatment.
• Stroke (including TIA), myocardial infarction, or other ischemic event, or thromboembolic event (eg, deep venous thrombosis, pulmonary embolism) within 6 months before randomization.
• Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation:
• \- Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction.

Sponsors & Collaborators

• Asan Medical Center: lead
• Ipsen: collaborator

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (1)

• Shah AY, Kotecha RR, Lemke EA, Chandramohan A, Chaim JL, Msaouel P, Xiao L, Gao J, Campbell MT, Zurita AJ, Wang J, Corn PG, Jonasch E, Motzer RJ, Sharma P, Voss MH, Tannir NM. Outcomes of patients with metastatic clear-cell renal cell carcinoma treated with second-line VEGFR-TKI after first-line immune checkpoint inhibitors. Eur J Cancer. 2019 Jun;114:67-75. doi: 10.1016/j.ejca.2019.04.003. Epub 2019 May 7.

  PMID: 31075726 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 19, 2021
• Study Start: March 1, 2021
• Primary Completion: February 28, 2023
• Study Completion: February 28, 2025
• Last Updated: January 19, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)