Cabozantinib in Advanced Salivary Gland Cancer Patients (Cabo ASAP)

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.

Study Overview

• Status: Terminated
• Conditions: Salivary Gland Cancer
• Intervention / Treatment: Drug: Cabozantinib

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
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500HB
      • Radboudumc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: cabometyx

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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
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)	Every OPD visit (starting with every 2 weeks, increasing to every 12 weeks after 1 year)
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.	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
clinical benefit rate	defined as the sum of complete remissions, partial responses, and patients with stable disease for >6 months.	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
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	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
quality of life based on the EORTC QLQ-C30 questionnaire		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		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		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	scale range 0-10, in which a higher score represents more pain	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).
response rate with continues tumor shrinkage end-points	response rate depicted in a waterfall plot	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
circulating tumor DNA levels	circulating tumor DNA levels will be assessed to evaluate whether treatment response and disease progression can be predicted.	circulating tumor DNA levels will be measured at baseline, at week 2, week 4 and before every evaluation CT/MRI scan.
correlation of c-MET immunohistochemical score with treatment response	c-MET immunohistochemical score ranges from 0 to 300.	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)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Ipsen
• Investigators: Principal Investigator: Carla ML van Herpen, MD, PhD, Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2018
• Primary Completion (Actual): November 6, 2019
• Study Completion (Actual): November 6, 2019

Study Registration Dates

• First Submitted: July 24, 2018
• First Submitted That Met QC Criteria: November 1, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: cabozantinib; overall survival; progression free survival; salivary gland cancer; adenoid cystic carcinoma; phase 2 clinical trial; salivary duct carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Mouth Neoplasms; Salivary Gland Neoplasms
• Other Study ID Numbers: MOHN14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• 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