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Renal Cell CancerPhase 2NCT04714697

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

A Phase 2 study testing Cabometyx in people with Renal Cell Cancer, run by Asan Medical Center at 1 site in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Renal Cell Cancer
What is being tested?
Cabometyx
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
201 participants
Where
1 siteSouth Korea
Study dates
1 Mar 2021to 28 Feb 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.
  • Cohort 3
  • Must have received VEGFR TKI (e.g., sunitinib, axitinib, pazopanib, or sorafenib) as the first-line systemic treatment and sequential PD-1 antibody or PD-L1 antibody, e.g., Pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, PDR001.
  • Subjects who experienced disease progression on second-line PD-1 or PD-L1 antibody or unacceptable toxicities.

Who cannot join

  • 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.
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  • 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.
  • Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before randomization.
  • Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization.
  • Clinically significant hematuria, hematemesis, or hemoptysis of above 0.5 teaspoon (2.5 ml) of red blood, or other history of significant bleeding (eg, pulmonary hemorrhage) within 3 months before enrollment.
  • Cavitray lung lesions or documented endobronchial lesions
  • Lesions invading major pulmonary blood vessels.
  • Other clinically significant disorders such as:
  • Active infection requiring systemic treatment, infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)- related illness.
  • Serious non-healing wound/ulcer/bone fracture.
  • Malabsorption syndrome.
  • Moderate to severe hepatic impairment (Child-Pugh B or C).
  • History of solid organ transplantation.
  • Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 1 month before IP administration. Complete wound healing from major surgery or minor surgery (eg, simple excision, tooth extraction) must have occurred 1 month before IP administration. Subjects with clinically relevant ongoing complications from prior surgery are not eligible.
  • Corrected QT interval calculated by the Fridericia formula (QTcF) above 500 msec within 1 month before randomization (see Section 5.5.4 for Fridericia formula).
  • Three ECGs must be performed. If the average of these three consecutive results for QTcF is or/and under 500 msec, the subject meets eligibility in this regard.
  • Pregnant or lactating females.
  • Inability to swallow tablets or capsules.
  • Previously identified allergy or hypersensitivity to components of the study treatment formulations.
  • Diagnosis of another malignancy within 1 year before randomization, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.

Trial locations and contacts

1 site in 1 country.

South Korea1 site

  • Asan Medical Center

    Seoul, 138-736

Other trials in South Korea

About this study

Official title: Cabozantinib as Subsequent Therapy to an Immune Checkpoint Based Therapy in Renal Cell Carcinoma, Phase 2, Interventional Study

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)

Read the detailed description

Cohort 1 (post nivolumab and ipilimumab combination): the subject who failed one prior line by nivolumab and ipilimumab Cohort 2 (post pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, or avelumab and axitinib): the subject who failed one prior line by PD-1/PD-L1 inhibitors in combination with VEGF TKI Cohort 3 (post sequential immunotherapy after VEGFR TKI): the subject who failed the second line by immunotherapy (PD-1 antibody or PD-L1 antibody) following the first line VEGFR TKI Subjects will receive study treatment as long as they continue to experience a clinical benefit in the investigator's opinion or until there is unacceptable toxicity or the need for subsequent systemic anticancer therapy. Treatment may continue after radiographic progression per RECIST 1.1 as long as the investigator believes that the subject is still receiving clinical benefit from study treatment and that the potential benefit of continuing study treatment outweighs potential risks.

Being tested
Cabometyx
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CabometyxDrug

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

Study groups in NCT04714697
Study groupRoleWhat they receive
Cohort 1(post nivolumab and ipilimumab combination)Experimentalthe subject who failed one prior line by nivolumab and ipilimumab
Receives: Drug: Cabometyx
Cohort 2 (post pembrolizumab plus axitinib, pembrolizumab plus lenvatinib, or avelumab and axitinib)Experimentalthe subject who failed one prior line by PD-1/PD-L1 inhibitors in combination with VEGF TKI
Receives: Drug: Cabometyx
Cohort 3 (post sequential immunotherapy after VEGFR TKI)No interventionthe subject who failed the second line by immunotherapy (PD-1 antibody or PD-L1 antibody) following the first line VEGFR TKI

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate

    Objective response rate , per RECIST 1.1, per investigator assessment

    Measured: up to 2years

Secondary outcomes (5)

  1. Time to response,

    Time to response, per RECIST 1.1, per investigator assessment

    Measured: up to 2years

  2. Duration of response

    Duration of response, per RECIST 1.1, per investigator assessment

    Measured: up to 2years

  3. Progression-free survival

    Progression-free survival , per RECIST 1.1, per investigator assessment

    Measured: up to 2years

  4. Overall survival

    Overall survival

    Measured: up to 5years

  5. Incidence of Treatment Adverse Events incidence of treatment Adverse Events (safety)

    Adverse Event, Serious adverse event by CTCAE 5.0

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2021
  2. Study start1 Mar 2021 (estimated)
  3. Primary completion28 Feb 2023 (estimated)
  4. Study completion28 Feb 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
201 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04714697
Sponsor's protocol ID
AT ASIA
Status last verified
Jan 2021
First submitted
7 Jan 2021
Last updated
19 Jan 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 31075726

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabometyx in people with Renal Cell Cancer, run by Asan Medical Center at 1 site in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 19 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: up to 2years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04714697, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2021.

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