E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent or metastatic head and neck cancer |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067821 |
E.1.2 | Term | Head and neck 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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of cabazitaxel in terms of non-progression at 6 weeks for the treatment of recurrent or metastatic head and neck cancer after failure of cisplatin, cetuximab and taxanes.
Non-progression will be assessed after centralized review of CT-scans.
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E.2.2 | Secondary objectives of the trial |
-To assess 6-week objective response rate
-To assess 6-week overall response rate
-To assess 1-year progression free survival (PFS)
-To assess 1-year overall survival
-To describe toxicity as per NCI-CTC-V4.0
-To assess quality of life |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1)Metastatic or recurrent Head and neck cancer
2)Progression after cisplatin, cetuximab and taxanes (drugs could have been administered alone or in combination) given for recurrent/metastatic disease
3)Age ≥ 18
4)ECOG performance status ≤ 2
5)At least one measurable lesion on CT-scan (as per RECIST criteria V1.1).
6)Life expectancy ≥ 3 months
7)Adequate hematologic function (neutrophils ≥ 1.5 x10^9/L , platelets ≥ 100x10^9/L; Hb ≥ 9.0 g/dL), renal function (clearance creatinine using the CKD-EPI formula (Chronic Kidney Disease Epidemiology group) ≥ 60 mL/min) and hepatic function (serum bilirubin ≤ 1 ULN; AST and ALT ≤ 2.5 x ULN).
8)Potentially reproductive patients must agree to use an effective contraceptive method while on treatment, beginning 2 weeks before the first dose of investigational product and for 6 months after the final dose of investigational product.
9)Women of childbearing potential must have a negative serum β-HCG pregnancy test within 14 days prior of enrolment and/or urine pregnancy test within 48 hours before the first administration of the study treatment.
10)Patients must be affiliated to a Social Security System.
11)Patient who have received the information sheet and signed the informed consent form.
12)Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures
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E.4 | Principal exclusion criteria |
1)Active concurrent malignancy
2)Progression in the 3 months after the completion of treatment for localized disease
3)Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as :
a- infection,
b- cardiac disease such as uncontrolled hypertension, congestive cardiac failure, ventricular arrhythmias, active ischemic heart disease, myocardial infarction within one year, LVEF > grade 2,
c- current active hepatic or biliary disease (with exception of subjects with Gilbert's syndrome, asymptomatic gallstones, liver metastasis or stable chronic liver disease per investigator assessment),
d- renal disease,
e- active GI tract ulceration, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Subjects with active, uncontrolled ulcerative colitis are also excluded,
f- severely impaired lung function (spirometry and DLCO 70% or less of normal and O2 saturation of 88% or less at rest on room air).
4)Patients must have recovered of previous toxicity of chemotherapy and must not have toxicity grade > 1 ; grade ≥ 2 for neuropathy and grade ≥ 2 for cutaneous rash after cetuximab (in the CTCAE v4.0)
5)Hypersensitivity to cabazitaxel, to other taxanes, or to any excipients of the formulation including polysorbate 80
6)Pregnant women, women who are likely to become pregnant or are breast-feeding.
7)Patients with significantly altered mental status prohibiting the understanding of the study or with 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.
8)Patients who received any other investigational drugs within the 14 days prior to the start of cabazitaxel.
9)Patients receiving radiation within 4 weeks prior to the first dose of study drug.
10)Patients already included in another therapeutic trial involving an experimental drug
11)Individual deprived of liberty or placed under the authority of a tutor.
12)Other primary tumors within the previous 3 years
13)Concomitant prohibited treatment. Concurrent or planned treatment with strong inhibitors or strong inducers of cytochrome P450 3A4/5 (see Appendix 6). A one week wash-out period is necessary for patients who are already on these treatments.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is non-progression at 6 weeks. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Secondary endpoints:
- 6 weeks objective response rate (as per RECIST 1.1)
- 6-week overall response rate (as per RECIST 1.1)
- 1-year progression free survival (PFS)
- 1-year overall survival
- The evaluation of safety
- Quality of life evaluated by the QLQ-C30 and H&N35 questionnaire at the inclusion, at C3 and at the end of treatment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life (QLQ-C30 and H&N35 questionnaire) |
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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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
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 | No |
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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |