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Salivary Gland CancerPhase 2Cabo ASAPNCT03729297

Cabozantinib in Advanced Salivary Gland Cancer Patients

A Phase 2 study testing Cabozantinib in people with Salivary Gland Cancer, run by Radboud University Medical Center at 1 site in Netherlands.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Phase 2 clinical trial on the efficacy of cabozantinib in locally advanced, recurrent and/or metastatic salivary gland cancer patients. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Salivary Gland Cancer
What is being tested?
Cabozantinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteNetherlands
Study dates
5 Sep 2018to 6 Nov 2019
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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Disease specific
  • locally advanced, recurrent, and/or metastatic SGC (excluding sarcomas and mesenchymal tumors)
  • c-MET positive disease
  • Measurable disease per RECIST version 1.1 Cohort-specific criteria
  • SDC cohort: direct inclusion (no objective tumor growth prior to inclusion needed)
  • ACC cohort: inclusion after objective growth in the last three months or complaints due to the disease
Show all 13Show fewer
  • Other SGC's: inclusion after objective growth in the last three months or complaints due to the disease General conditions
  • Age ≥18 years
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Normal number of neutrophils and thrombocytes
  • Liver function: ALT and AST < 2.5 x upper limit of normal (ULN), total bilirubin ≤ 1.5 x ULN (except for Gilbert's syndrome), serum albumin ≥28 g/L
  • Renal function: creatinine < 1.5 x ULN or calculated creatinine clearance ≥ 40 ml/min, Urine protein/creatinine ratio ≤113.1 mg/mmol (≤1 mg/mg) or 24-hour urine protein <1 g
  • Hemoglobin A1c (HbA1c) ≤ 8% or a fasting serum glucose ≤ 9 mmol/l

Who cannot join

  • General conditions
  • A known allergy for cabozantinib or its components
  • Long QT-syndrome
  • Pregnancy or lactation
  • Patients (M/F) with reproductive potential not implementing adequate contraceptives measures
  • Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery and stable for at least 3 months before inclusion
Show all 12Show fewer
  • Major surgery within 3 months before randomization. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery at least 10 days before inclusion
  • Uncontrolled illness including, but not limited to cardiovascular disorders including symptomatic congestive heart failure, unstable angina pectoris, or serious cardiac arrhythmias, uncontrolled hypertension defined as sustained systolic BP > 150 mm Hg, or diastolic BP > 100 mm Hg, stroke (including TIA), myocardial infarction, or other ischemic event within 6 months before inclusion, serious active infections Concomitant treatments
  • Concomitant (or within 4 weeks before inclusion) administration of any other experimental drug under investigation.
  • Concurrent treatment with any other anti-cancer therapy.
  • Concomitant anticoagulation. Low dose aspirin for cardioprotection and low dose LMWH are permitted.
  • Radiation therapy within the last 4 weeks before inclusion

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • Radboudumc

    Nijmegen, Gelderland, 6500HB

Other trials in Netherlands

About this study

Official title: The Efficacy of Cabozantinib in Advanced SAlivary Gland Cancer Patients, a Phase II Clinical Trial

Phase 2 clinical trial on the efficacy of cabozantinib in locally advanced, recurrent and/or metastatic salivary gland cancer patients.

Read the detailed description

Rationale: Salivary gland cancer (SGC) is a rare cancer with 24 histological subtypes. Treatment options for locally advanced and/or metastatic SGC are limited. The tyrosine kinase inhibitor cabozantinib suppresses tumor growth, angiogenesis, and metastasis, and has been approved for renal cell carcinoma and thyroid cancer. Cabozantinib may also be of value in advanced SGC because c-MET, one of the targets of cabozantinib, is frequently overexpressed in SGC.

Objectives: To assess the objective response rate (ORR), progression free survival (PFS), overall survival (OS), duration of response (DoR), toxicity, and quality of life (QoL) of patients with advanced SGC treated with cabozantinib in 3 cohorts: salivary duct carcinoma (SDC), adenoid cystic carcinoma (ACC), other SGC's.

Study design: Single arm, single center, phase II clinical trial in 3 cohorts: ACC, SDC and other SGC's.

Study population: Patient with c-MET positive, locally advanced, recurrent, and/or metastatic SGC.

Intervention: Cabozantinib tablets 60 mg once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw for a maximum duration of 2 years.

Being tested
Cabozantinib
Keywords
salivary gland cancer, adenoid cystic carcinoma, salivary duct carcinoma, cabozantinib, progression free survival, overall survival, phase 2 clinical trial
Medical subject headings
Salivary Gland Neoplasms, Carcinoma, Adenoid Cystic

What participants receive

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

  • CabozantinibDrug

    Also called cabometyx

    cabozantinib tablets (Cabometyx®) once daily until progressive disease, intolerable toxicity, or investigator and/or patient decision to withdraw for a maximum duration of 2 years.

Study groups in NCT03729297
Study groupRoleWhat they receive
cabozantinibExperimentalcabozantinib 60 mg tablets OD
Receives: Drug: Cabozantinib

What is being measured

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

  1. overall response rate

    Response will be measured according to RECIST version 1.1, the overall response rate is defined as the sum of the complete remissions plus partial responses. The best response will be used in each patient

    Measured: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the response rate until progressive disease

Secondary outcomes (12)

  1. progression free survival

    progression free survival is defined as time from study enrollment until disease progression or death. Outcome will be scored as 'progressed' or 'censored' according to the FDA guidance for industry of clinical trial endpoints.

    Measured: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses PFS until progressive disease

  2. overall survival

    overall survival is defined as time from study enrollment until date of death of any cause. Analysis of OS will be done at the end of the study (study related follow-up will be until 3 years after start of treatment)

    Measured: Every OPD visit (starting with every 2 weeks, increasing to every 12 weeks after 1 year)

  3. duration of response

    duration of response is defined as time from study enrollment until date of documented tumor progression or death. Only patients with a CR or PR will be included in the assessment of duration of response.

    Measured: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses duration of response until progressive disease

  4. clinical benefit rate

    defined as the sum of complete remissions, partial responses, and patients with stable disease for >6 months.

    Measured: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the clinical benefit rate until progressive disease

  5. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    adverse events will be reported as descriptive statistics in a table

    Measured: through study completion. At every visit AE's will be recorded. Scheduled visits will be planned 2, 4, 6, 8, 12, 16, 20, 24, 32, 40, 48, 56, 68, 80, 92 and 104 weeks after start of treatment

  6. quality of life based on the EORTC QLQ-C30 questionnaire

    Measured: patients are asked to fill in the questionnaires in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication).

  7. quality of life based on the EORTC QLQ-H&N35 questionnaire

    Measured: patients are asked to fill in the questionnaires in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication).

  8. quality of life based on the PSSHN questionnaire

    Measured: patients are asked to fill in the questionnaire in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication)..

  9. pain level assessed by the VAS(visual analog scale) questionnaire

    scale range 0-10, in which a higher score represents more pain

    Measured: patients are asked to fill in the questionnaire in week 0 (before start of treatment), week 8, 16, 24, 40, 56, and at progressive disease (up to 104 weeks after start of study medication).

  10. response rate with continues tumor shrinkage end-points

    response rate depicted in a waterfall plot

    Measured: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the response rate until progressive disease

  11. circulating tumor DNA levels

    circulating tumor DNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted.

    Measured: circulating tumor DNA levels will be measured at baseline, at week 2, week 4 and before every evaluation CT/MRI scan.

  12. correlation of c-MET immunohistochemical score with treatment response

    c-MET immunohistochemical score ranges from 0 to 300.

    Measured: c-MET will be measured once (before treatment). Response will be measured every 8 weeks (first year) and every 12 weeks (second year of treatment)

Timeline

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

  1. First posted2 Nov 2018
  2. Study start5 Sep 2018
  3. Primary completion6 Nov 2019
  4. Study completion6 Nov 2019

Why it stopped: safety issues

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
Not applicable
Intervention model
Single group
Model description
3 cohorts: * adenoid cystic carcinoma * salivary duct carcinoma * other subtypes of salivary gland cancer sample size: The Simon two-stage design will be used, The first stage consists of 9 patients per cohort ((1) SDC, (2) ACC) evaluable for response. If 0 responses out of the first 9 evaluable patients are observed, the study will be stopped. In any other situation, the study will be continued until 17 patients are evaluable for response per cohort. If ≤2 responses are observed the study will accept the null hypothesis. If \>2 responses are observed, the null hypothesis will be rejected. In the third cohort (other SGC) 9 patients will be included to evaluate the efficacy of cabozantinib in other subtypes of c-MET positive SGC. Because different subtypes are included in this cohort, these results are hypothesis forming but will not be used for statistical analysis. Therefore, this study cohort will be closed after the first stage with 9 patients.
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03729297
Sponsor's protocol ID
MOHN14
Acronym
Cabo ASAP
Status last verified
Nov 2019
First submitted
24 Jul 2018
Last updated
12 Mar 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Weijers JAM, de Bitter TJJ, Verhaegh GW, van Boxtel W, Uijen MJM, van Engen-van Grunsven ACH, Driessen CML, Schalken JA, Ligtenberg MJL, van Herpen CML. Exploring the potential of circulating tumour DNA to monitor treatment response in salivary duct carcinoma patients of the CABO-ASAP trial. Oral Oncol. 2023 Dec;147:106620. doi: 10.1016/j.oraloncology.2023.106620. Epub 2023 Nov 6. No abstract available.

    PubMed 37939426

  • van Boxtel W, Uijen MJM, Krens SD, Dijkema T, Willems SM, Jonker MA, Pegge SAH, van Engen-van Grunsven ACH, van Herpen CML. Excessive toxicity of cabozantinib in a phase II study in patients with recurrent and/or metastatic salivary gland cancer. Eur J Cancer. 2022 Jan;161:128-137. doi: 10.1016/j.ejca.2021.10.033. Epub 2021 Dec 14.

    PubMed 34920917

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cabozantinib in people with Salivary Gland Cancer, run by Radboud University Medical Center at 1 site in Netherlands.

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 13 inclusion and 12 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: stopped early, as of the sponsor's last update on 12 Mar 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 Netherlands. 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?

The study was stopped early (reason given: safety issues). 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?

overall response rate (time frame: every 8 weeks (first year of treatment) and every 12 weeks (second year of treatment) a CT/MRI scan will be made to asses the response rate until progressive disease). 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 NCT03729297, which also lists 2 linked publications.

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 12 Mar 2021.

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