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Cabozantinib in Advanced Salivary Gland Cancer Patients (Cabo ASAP)

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ClinicalTrials.gov Identifier: NCT03729297
Recruitment Status : Terminated (safety issues)
First Posted : November 2, 2018
Last Update Posted : March 12, 2021
Sponsor:
Collaborator:
Ipsen
Information provided by (Responsible Party):
Radboud University

Tracking Information
First Submitted Date  ICMJE July 24, 2018
First Posted Date  ICMJE November 2, 2018
Last Update Posted Date March 12, 2021
Actual Study Start Date  ICMJE September 5, 2018
Actual Primary Completion Date November 6, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2018)
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 ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 8, 2018)
  • progression free survival [ 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 PFS until progressive disease ]
    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.
  • overall survival [ Time Frame: Every OPD visit (starting with every 2 weeks, increasing to every 12 weeks after 1 year) ]
    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)
  • duration of response [ 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 duration of response until progressive disease ]
    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.
  • clinical benefit 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 clinical benefit rate until progressive disease ]
    defined as the sum of complete remissions, partial responses, and patients with stable disease for >6 months.
  • Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: 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 ]
    adverse events will be reported as descriptive statistics in a table
  • quality of life based on the EORTC QLQ-C30 questionnaire [ Time Frame: 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). ]
  • quality of life based on the EORTC QLQ-H&N35 questionnaire [ Time Frame: 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). ]
  • quality of life based on the PSSHN questionnaire [ Time Frame: 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).. ]
  • pain level assessed by the VAS(visual analog scale) questionnaire [ Time Frame: 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). ]
    scale range 0-10, in which a higher score represents more pain
  • response rate with continues tumor shrinkage end-points [ 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 ]
    response rate depicted in a waterfall plot
  • circulating tumor DNA levels [ Time Frame: circulating tumor DNA levels will be measured at baseline, at week 2, week 4 and before every evaluation CT/MRI scan. ]
    circulating tumor DNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted.
  • correlation of c-MET immunohistochemical score with treatment response [ Time Frame: 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) ]
    c-MET immunohistochemical score ranges from 0 to 300.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2018)
  • progression free survival [ 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 PFS until progressive disease ]
    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.
  • overall survival [ Time Frame: Every OPD visit (starting with every 2 weeks, increasing to every 12 weeks after 1 year) ]
    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)
  • duration of response [ 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 duration of response until progressive disease ]
    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.
  • clinical benefit 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 clinical benefit rate until progressive disease ]
    defined as the sum of complete remissions, partial responses, and patients with stable disease for >6 months.
  • Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: throug 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 ]
    adverse events will be reported as descriptive statistics in a table
  • quality of life based on the EORTC QLQ-C30 questionnaire [ Time Frame: 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). ]
  • quality of life based on the EORTC QLQ-H&N35 questionnaire [ Time Frame: 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). ]
  • quality of life based on the PSSHN questionnaire [ Time Frame: 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).. ]
  • pain level assessed by the VAS(visual analog scale) questionairre [ Time Frame: 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). ]
    scale range 0-10, in which a higher score represents more pain
  • response rate with continues tumor shrinkage end-points [ 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 ]
    response rate depicted in a waterfall plot
  • circulating tumor DNA levels [ Time Frame: circulating tumor DNA levels will be measured at baseline, at week 2, week 4 and before every evaluation CT/MRI scan. ]
    circulating tumor DNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted.
  • correlation of c-MET immunohistochemical score with treatment response [ Time Frame: 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) ]
    c-MET immunohistochemical score ranges from 0 to 300.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cabozantinib in Advanced Salivary Gland Cancer Patients
Official Title  ICMJE The Efficacy of Cabozantinib in Advanced SAlivary Gland Cancer Patients, a Phase II Clinical Trial
Brief Summary Phase 2 clinical trial on the efficacy of cabozantinib in locally advanced, recurrent and/or metastatic salivary gland cancer patients.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Intervention 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)
Primary Purpose: Treatment
Condition  ICMJE Salivary Gland Cancer
Intervention  ICMJE Drug: Cabozantinib
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.
Other Name: cabometyx
Study Arms  ICMJE Experimental: cabozantinib
cabozantinib 60 mg tablets OD
Intervention: Drug: Cabozantinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 20, 2019)
25
Original Estimated Enrollment  ICMJE
 (submitted: November 1, 2018)
43
Actual Study Completion Date  ICMJE November 6, 2019
Actual Primary Completion Date November 6, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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
  • 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

Exclusion Criteria:

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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Netherlands
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03729297
Other Study ID Numbers  ICMJE MOHN14
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Radboud University
Study Sponsor  ICMJE Radboud University
Collaborators  ICMJE Ipsen
Investigators  ICMJE
Principal Investigator: Carla ML van Herpen, MD, PhD Radboud University
PRS Account Radboud University
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP