| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061934 |
| E.1.2 | Term | Salivary gland cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| 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 |
The two main objectives of the study are:
♦ To assess the efficacy of androgen deprivation therapy in treatment naïve patients with recurrent and/or metastatic, androgen receptor expressing, salivary gland cancers (SGCs). The primary measure of efficacy is Progression-Free Survival.
♦ To describe the effect of androgen deprivation therapy in pretreated patients with recurrent and/or metastatic, androgen receptor expressing SGCs. The main measure of efficacy is response to treatment. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
At patient registration step:
- Histologically proven diagnosis of recurrent and/or metastatic salivary duct cancer; adenocarcinoma NOS; and androgen receptor expression level of = 6 in nuclei of neoplastic cells based on central review. Sufficient tissue must be available either from a historical sample or a new biopsy must be done as a part of this study and sent for central review for patients to be enrolled in both cohorts;
- Presence of at least one uni-dimensional measurable lesion by CT-scan or MRI according to RECIST criteria version 1.1 (target lesion). A lesion previously treated with radiotherapy can be chosen as a target lesion only if progression in the respective lesion has been demonstrated during or following radiotherapy;
- Patients older than 18 years old;
- Performance Status ECOG 0-1;
- Before patient registration, written informed consent must be given according to ICH/GCP, and national/local regulations.
At patient enrollment step:
- Central pathology confirmation of androgen receptor expression
- Adequate bone marrow function (within 2 weeks prior to treatment start):
WBC ≥ 3.5/109L
absolute neutrophil count ≥ 1,5x109/L
hemoglobin > 10 g/dL or > 6.20 mmol/L
platelet count ≥ 100x109/L
- Adequate liver function (within 2 weeks prior to treatment start):
AST < 2.5 times upper limit of normal
ALT < 2.5 times upper limit of normal
bilirubin < 1.5 times upper limit of normal
- Adequate renal function (within 2 weeks prior to treatment start):
serum creatinine level (≤ 1.3 mg/dL)
calculated creatinine clearance ≥ 60 mL/min based on the standard Cockcroft and Gault formula (Appendix C)
- Adequate cardiac function as demonstrated by a clinically normal 12 lead ECG. Additionally for patients who will receive Cisplatin and Doxorubicin adequate cardiac function should be demonstrated by a left ventricular ejection fraction (LVEF) ≥ 50% (within 2 weeks prior to treatment start).
- Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within 1 week prior to the first dose of study treatment;
- Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment. A highly effective method of birth control is defined as those which result in low failure rate (i.e. less than 1% per year) when used consistently and correctly; women should not breastfeed a baby while on this study.
Specific for Cohort A:
No previous chemotherapy for recurrent/metastatic disease (previous chemotherapy given concomitantly with RT in the past is allowed, including cisplatin but it should be completed at least 6 months before enrollment).
Specific to Cohort B:
Patients who received chemotherapy for recurrent and metastatic disease and subsequently progress will be included in this cohort. |
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| E.4 | Principal exclusion criteria |
At patient registration step:
- Patients with bone disease or brain disease as the sole disease site; brain metastases are allowed in the case of systemic disease, but must have been treated at least 4 weeks before enrollment and must be stable thereafter;
- No cardiac abnormalities as demonstrated by:
recent history of congestive heart failure
unstable angina within the past 3 months
cardiac arrhythmia
myocardial infarction
congenital long QTc prolongation
stroke
TIA within the past 6 months;
♦ History of allergic reactions attributed to compounds of similar chemical or biological composition to cis/carboplatin, paclitaxel, doxorubicin, bicalutamide or triptorelin;
- Active second malignancy during the last five years except non melanomatous skin cancer or carcinoma in situ of the cervix;
- Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial;
At patient enrollment step:
- Participation in another interventional clinical trial in the preceding 4 weeks prior to enrollment |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Cohort A (treatment naïve patients):
Progression-Free Survival according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 and/or Prostate Cancer Clinical Trials Working Group (PCWG2) (2007) for bone lesions, or death, whichever comes first.
Cohort B (pretreated patients):
Best Overall Response defined according to RECIST v 1.1. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment RECIST criteria evaluation will be performed at week 8, 16 and 28 and every 12 weeks thereafter (+/- 1 week) through head and neck and thorax CT scan or head and neck MRI. PCWG2 evaluation will be performed at the same time-points through bone scans.
After the end of treatment and up to disease progression
imaging will be done every 12 weeks and other investigations should be done if clinically indicated or based on institutional standard practice. |
|
| E.5.2 | Secondary end point(s) |
For treatment-naïve patients:
- Best Overall Response defined according to RECIST v 1.1
- Overall Survival
- Toxicity
For pre-treated patients:
- Progression Free Survival
- Overall Survival
- Toxicity |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
The time-points for evaluation of Best Overall Response and Progression Free Survival are the same as for the primary endpoint; at week 8, 16 and 28 and every 12 weeks thereafter (+/- 1 week).
In addition overall survival will be assessed through long-term follow-up once every year.
Toxicity will be assessed prior to each treatment cycle and at the end of treatment.
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| 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 | No |
| E.6.5 | Efficacy | No |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| 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) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 28 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Austria |
| Belgium |
| France |
| Germany |
| Greece |
| Hungary |
| Italy |
| Netherlands |
| Portugal |
| United Kingdom |
| United States |
|
| 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
|
End of study occurs when all of the following criteria have been satisfied:
1. Thirty days after all patients have stopped protocol treatment
2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
3. The database has been fully cleaned and frozen for this analysis |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 6 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 6 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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