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Cabozantinib in Advanced Salivary Gland Cancer Patients (Cabo ASAP)

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ClinicalTrials.gov Identifier: NCT03729297
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Ipsen
Information provided by (Responsible Party):
Radboud University

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

Condition or disease Intervention/treatment Phase
Salivary Gland Cancer Drug: Cabozantinib Phase 2

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
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
Official Title: The Efficacy of Cabozantinib in Advanced SAlivary Gland Cancer Patients, a Phase II Clinical Trial
Actual Study Start Date : September 5, 2018
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : March 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: cabozantinib
cabozantinib 60 mg tablets OD
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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.

  4. 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.

  5. 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

  6. 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). ]
  7. 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). ]
  8. 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).. ]
  9. 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

  10. 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

  11. 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.

  12. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03729297


Contacts
Contact: Cala ML van Herpen, MD, PhD +31243618800 carla.vanherpen@radboudumc.nl
Contact: Wim van Boxtel, MD +31243618800 wim.vanboxtel@radboudumc.nl

Locations
Netherlands
Radboudumc Recruiting
Nijmegen, Gelderland, Netherlands, 6500HB
Contact: Carla ML van Herpen, MD, PhD    024 3667251    Carla.vanHerpen@radboudumc.nl   
Contact: Wim van Boxtel, MD    +31625034690    Wim.vanBoxtel@radboudumc.nl   
Sponsors and Collaborators
Radboud University
Ipsen
Investigators
Principal Investigator: Carla ML van Herpen, MD, PhD Radboud University
  Study Documents (Full-Text)

Documents provided by Radboud University:

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT03729297     History of Changes
Other Study ID Numbers: MOHN14
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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

Keywords provided by Radboud University:
salivary gland cancer
adenoid cystic carcinoma
salivary duct carcinoma
cabozantinib
progression free survival
overall survival
phase 2 clinical trial

Additional relevant MeSH terms:
Salivary Gland Neoplasms
Mouth Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Neoplasms
Mouth Diseases
Stomatognathic Diseases
Salivary Gland Diseases