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Cabozantinib in Advanced Salivary Gland Cancer Patients (Cabo ASAP)

Primary Purpose

Salivary Gland Cancer

Status

Terminated

Phase

Phase 2

Locations

Netherlands

Study Type

Interventional

Intervention

Cabozantinib

About this trial

This is an interventional treatment trial for Salivary Gland Cancer focused on measuring salivary gland cancer, adenoid cystic carcinoma, salivary duct carcinoma, cabozantinib, progression free survival, overall survival, phase 2 clinical trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Radboudumc

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

cabozantinib

Arm Description

cabozantinib 60 mg tablets OD

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

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)

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.

clinical benefit rate

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

adverse events will be reported as descriptive statistics in a table

quality of life based on the EORTC QLQ-C30 questionnaire

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

quality of life based on the PSSHN questionnaire

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

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

response rate with continues tumor shrinkage end-points

response rate depicted in a waterfall plot

circulating tumor DNA levels

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

c-MET immunohistochemical score ranges from 0 to 300.

Full Information

NCT ID

NCT03729297

First Posted

July 24, 2018

Last Updated

March 11, 2021

Sponsor

Radboud University Medical Center

Collaborators

Ipsen

1. Study Identification

Unique Protocol Identification Number

NCT03729297

Brief Title

Cabozantinib in Advanced Salivary Gland Cancer Patients

Acronym

Cabo ASAP

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Terminated

Why Stopped

safety issues

Study Start Date

September 5, 2018 (Actual)

Primary Completion Date

November 6, 2019 (Actual)

Study Completion Date

November 6, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Radboud University Medical Center

Collaborators

Ipsen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Salivary Gland Cancer

Keywords

salivary gland cancer, adenoid cystic carcinoma, salivary duct carcinoma, cabozantinib, progression free survival, overall survival, phase 2 clinical trial

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

cabozantinib

Arm Type

Experimental

Arm Description

cabozantinib 60 mg tablets OD

Intervention Type

Drug

Intervention Name(s)

Cabozantinib

Other Intervention Name(s)

cabometyx

Intervention Description

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.

Primary Outcome Measure Information:

Title

overall response rate

Description

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

Secondary Outcome Measure Information:

Title

progression free survival

Description

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

Title

overall survival

Description

Time Frame

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

Title

duration of response

Description

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

Title

clinical benefit rate

Description

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

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

Title

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

Description

adverse events will be reported as descriptive statistics in a table

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

Title

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).

Title

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).

Title

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)..

Title

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

Description

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

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).

Title

response rate with continues tumor shrinkage end-points

Description

response rate depicted in a waterfall plot

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

Title

circulating tumor DNA levels

Description

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

Time Frame

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

Title

correlation of c-MET immunohistochemical score with treatment response

Description

c-MET immunohistochemical score ranges from 0 to 300.

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)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Carla ML van Herpen, MD, PhD

Organizational Affiliation

Radboud University Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Radboudumc

City

Nijmegen

State/Province

Gelderland

ZIP/Postal Code

6500HB

Country

Netherlands

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

34920917

Citation

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.

Results Reference

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Cabozantinib in Advanced Salivary Gland Cancer Patients

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