E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Salivary gland cancer |
Speekselklierkanker |
|
E.1.1.1 | Medical condition in easily understood language |
salivary gland cancer |
Speekselklierkanker |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Assess the overall response rate (ORR) of cabozantinib in advanced salivary gland cancer patients. ORR is defined as the sum of the complete remissions plus partial responses. The best response will be used in each patient.
|
het bepalen van de overall response rate (ORR) van cabozantinib bij gevorderd speekselkliercarcinoom. ORR is gedefinieerd als de som van het aantal complete remissies en partiele responsen. de beste respons zal bij iedere patiënt worden gebruikt. |
|
E.2.2 | Secondary objectives of the trial |
- Assess the progression free survival (PFS). PFS will be defined as time from study enrollment until disease progression or death.
- Assess the overall survival (OS). OS will be defined as time from study enrollment until date of death of any cause.
- Asses the duration of response (DoR). DoR is defined as time from study enrollment until date of documented tumor progression or death
- Assess the toxicity of cabozantinib. Toxicity will be scored according to NCI CTC common criteria v 4.0.10
- Assess the quality of life (QoL) of patients treated with cabozantinib using EORTC questionnaires.
- Assess the response rate by using continuous tumor shrinkage end-points.
- circulating tumor DNA will be assessed to evaluate whether response and disease progression can be predicted.
|
- bepalen van de progressie vrije overleving.
- bepalen van de totale overleving.
- bepalen van de responsduur.
- bepalen van de toxiciteit van cabozantinib
- bepalen van de kwaliteit van leven van patiënten die worden behandeld met cabozantinib
- bepalen van de response rate door het gebruik van continue tumor krimp eindpunten/
- circulerend tumor DNA zal worden bepaald om te bekijken of respons en ziekteprogressie kan worden voorspeld. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to be eligible to participate in this study, a patient must meet all of the following criteria:
- Disease specific
- locally advanced, recurrent, and/or metastatic SGC (excluding sarcomas and mesenchymal tumors)
- c-MET positive disease (see paragraph 4.1)
- 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 albumine ≥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 |
om deel te nemen moet een patiënt al de volgende criteria voldoen:
- ziekte specifiek
- lokaal gevorderd, lokaal recidiverend en of gemetastaseerd speekselkliercarcinoom (geen sarcomen en mesenchymale tumoren)
- c-MET positieve ziekte
- meetbare ziekte volgens RECIST version 1.1
- Cohort-specifieke criteria
- SDC cohort: directe inclusie (geen objectieve tumorgroei nodig)
- ACC cohort: Inclusie na objectieve tumorgroei of klachten door de ziekte
- andere SGC’s: Inclusie na objectieve tumorgroei of klachten door de ziekte
- algemene voorwaarden
- leeftijd ≥18 jaar
- Eastern Cooperative Oncology Group performance status van 0 of 1.
- Normaal aantal neutrofielen en thrombocyten
- Lever functie: ALT en AST < 2.5 x upper limit of normal (ULN), Totaal bilirubine ≤ 1.5 x ULN (behalve voor Gilbert’s syndroom),
serum albumine ≥28 g/L
- nierfunctie: Creatinine < 1.5 x ULN or berekende klaring ≥ 40 ml/min,
Urine eiwit/creatinine ratio ≤113.1 mg/mmol (≤1 mg/mg) of 24-hour urine eiwit <1 g
- Hemoglobin A1c (HbA1c) ≤ 8% of een nuchter serum glucose ≤ 9 mmol/l |
|
E.4 | Principal 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 |
- algemene omstandigheden
- allergie voor cabozantinib
- Lang QT-syndroom
- zwangerschap of borstvoeding
- Patienten (M/V) in reproductieve levensfase die geen adequate contraceptive maatregelen nemen
- bekende hersenmetastasen of craniale epidurale ziekte tenzij adequaa behandeld met radiotherapie en/of chirurgie of stabiel voor
ten minste 3 maanden voor inclusie
- grote chirurgie binnen 3 maanden voor inclusie. complete wondgenezing moet voor 1 maand bestaan. voor kleine chirurgie geldt
een termijn van 10 dagen.
- ongecontrollerde ziekte, inclusief, maar niet gelimiteerd tot:
- hartfalen, ritmestoornissen
- ongecontroleerde hypertensie
- beroerte of TIA, of ander ischemisch event 6 maanden voor inclusie
- Serieuze actieve infecties
- Concomitante behandelingen
- een andere experimentele behandeling
- een andere anti kanker behandeling
- Concomitante antistolling. lage dosis aspirine en lage dosis LMWH's zijn toegestaan.
- Radiotherapie binnen 4 weken voor inclusie |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Assess the overall response rate (ORR) of cabozantinib in advanced salivary gland cancer patients. ORR is defined as the sum of the complete remissions plus partial responses. The best response will be used in each patient.
|
het bepalen van de overall response rate (ORR) van cabozantinib bij gevorderd speekselkliercarcinoom. ORR is gedefinieerd als de som van het aantal complete remissies en partiele responsen. de beste respons zal bij iedere patiënt worden gebruikt. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
in the first year of treatment, a evaluation CT will be made every 8 weeks, in the second year of treatment, an evaluation CT will be made every 12 weeks. |
in het eerste jaar van behandeling wordt iedere 8 weken een CT gemaakt, in het 2e jaar iedere 12 weken. |
|
E.5.2 | Secondary end point(s) |
- Assess the progression free survival (PFS). PFS will be defined as time from study enrollment until disease progression or death.
- Assess the overall survival (OS). OS will be defined as time from study enrollment until date of death of any cause.
- Asses the duration of response (DoR). DoR is defined as time from study enrollment until date of documented tumor progression or death
- Assess the toxicity of cabozantinib. Toxicity will be scored according to NCI CTC common criteria v 4.0.10
- Assess the quality of life (QoL) of patients treated with cabozantinib using EORTC questionnaires.
- Assess the response rate by using continuous tumor shrinkage end-points.
- circulating tumor DNA will be assessed to evaluate whether response and disease progression can be predicted. |
- bepalen van de progressie vrije overleving.
- bepalen van de totale overleving.
- bepalen van de responsduur.
- bepalen van de toxiciteit van cabozantinib
- bepalen van de kwaliteit van leven van patiënten die worden behandeld met cabozantinib
- bepalen van de response rate door het gebruik van continue tumor krimp eindpunten/
- circulerend tumor DNA zal worden bepaald om te bekijken of respons en ziekteprogressie kan worden voorspeld. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
progression free surival and duration of response will be evaluated using CT-scans (as the primary outcome).
overall survival and toxicity will be evaluated at every visit.
quality of life quesionairres will be taken 7 times, blood for circulating tumor DNA first every 2 week, en thereafter at every CT. |
progressievrije overleving en responsduur worden middels CT geevalueerd (zie primaire uitkomst)
overall survival en toxiciteit worden bij ieder bezoek geevalueerd.
kwaliteit van leven vragenlijsten worden 7x afgenomen, bloed voor circulerend tumor DNA eerst iedere 2 weken, en daarna bij iedere CT |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
last visit of last subject |
laatste bezoek van laatste patient |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |