Cabozantinib in Advanced Salivary Gland Cancer Patients

Salivary Gland Cancer Clinical Trial

— Cabo ASAP  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03729297
• Other study ID #: MOHN14
• Status: Terminated
• Phase: Phase 2
• Start date: September 5, 2018
• Est. completion date: November 6, 2019

Study information

• Verified date: November 2019
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: November 6, 2019
• Est. primary completion date: November 6, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Salivary Gland Cancer
• Salivary Gland Neoplasms

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Radboudumc	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Ipsen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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).
Secondary	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).
Secondary	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)..
Secondary	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).
Secondary	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
Secondary	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.
Secondary	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)