E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with five different tumour entities will be included in the present trial:
1. squamous cell carinoma of the head and neck 2. breast cancer 3. ovarian cancer 4. soft tissue sarcoma 5. melanoma |
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MedDRA Classification |
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 document anti-tumour activity and further define safety profile and collect data for population pharmacokinetics |
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E.2.2 | Secondary objectives of the trial |
The study will document:
*Clinical benefit defined as the rate of responders and stable patients (RECIST) *Duration of response in responding patients *Overall progression free survival *Overall survival |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
*Measurable disease based on RECIST with target lesion of at least 20 mm *Documented progressive disease based on RECIST and proven by imaging prior to to study entry *No clinical evidence of brain metastases *Administration of any prior systemic treatment for the current malignancy must have been completed for at least 4 weeks before the first treatment in this trial including chemotherapy, radiotherapy, immunotherapy, hormonal therapy and treatment with monoclonal antibodies or small molecule tyrosine kinase inhibitors and others. *At least 18 years old. *ECOG performance score (PS) 0-2 *Adequate haematological function *Adequate renal function *Bilirubin inferior or equal to 1.5 times ULN, AST/ALT inferior or equal to 2.5 times ULN in absence of liver metastases and inferior or equal to 5 times ULN in case of liver metastases. *No persistence of toxicities from any prior anti-cancer therapy which are deemed clinically relevant. *All patients (male and female) must use effective contraception if of reproductive potential. Females must not be pregnant or lactating at screening *Absence of any psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up schedule; such conditions should be assessed with the patient before registering in the trial. *No other previous and active malignancy for at least 5 years with the exception of cone biopsied carcinoma of the cervix and adequately treated basal or squamous cell skin carcinoma. *No concomitant intercurrent illnesses including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness or social situation that would limit compliance with trial requirement or which are considered relevant for the evaluation or the efficacy or safety of the trial drug. *No treatment with any other investigational drug within the past four weeks or within less than four half-life times of the investigational drug before treament with the trial drug (whatever is the longest period) *No major surgery within 4 weeks prior to first treatment with the trial drug. *Before the first trial specific procedures are undetaken, written informed consent must be obtained. |
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E.4 | Principal exclusion criteria |
Tumour specific eligibility criteria:
Head and neck cancer *Histologically or cytologically proven squamous cell carcinoma of the head and neck (excluding nasopharyngeal primaries) *Patient presenting with new non-irradiated lesions in pre-irraditaed field as target lesions are eligible. *Recurrent or metastatic disease, no longer suitable for local therapy. *Prior use of chemotherapy/chemoradiotherapy/EGFR inhibitors for the treatment of the primary disease/non-metastatic disease is allowed. *No prior chemotherapy for recurrent or metastatic advanced disease is allowed.
Breast Cancer *Histologically proven recurrent or metastatic adenocarcinoma of the breast which failed prior taxane and anthracycline therapy. *Patient must have had a minimum of one line and a maximum of 2 lines of chemotherapy treatment given either as adjuvant treatment or for recurrence / metastatic disease. *Patients who do not qualify for Her 2 based therapy.
Ovarian Cancer *Histologically proven epithelial ovarian cancer. *Metastatic or inoperable locally advanced disease. *Patients either progressing under or relapsing within 6 months of compeltion of any line of platinum and taxane-based therapeutic regimen for advanced disease.
Soft tissue sarcoma *Histologically proven advanced and/or metastatic malignant soft tissue sarcoma of high or intermediate grade and one of the histologies defined by the WHO classification 2002: leiomyosarcoma, adipocytic sarcoma, synovial sarcoma and others but which exclude embryonic rhabdomyosarcoma, chondrosarcoma, osteosarcoma, Ewing tumours/PNET, GIST, dermatofibrosarcoma protuberans, inflammatory myofibroblastic sarcoma, neuroblastoma, malignant mesothelioma, mixed mesodermal tumours of the uterus. *Patients must have received no more than one combination or two single agents of chemotherapy regimen for advanced disease and treatment must have included an anthracycline if not medically contra-indicated.
Melanoma *Patients with histologically proven metastic malignant melanoma. Ocular melanomas are excluded. *Patients must either not have received any prior chemotherapy for recurrent / metastatic disease or have received one line of prior chemotherapy as long as LDH smaller than or equal to 2 ULN. One prior line of immunotherpay is allowed. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end-point is to document the confirmed response rate (complete and partial response - CR and PR) as defined by RECIST. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 | Information not present in EudraCT |
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
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End of study is defined in the protocol and occurs when any of the following criteria are met: -The trial is mature for the analysis of the primary end point as defined in the protocol -The database has been fully cleaned and frozen for this analysis for the particular tumour type |
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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 | |
E.8.9.1 | In the Member State concerned months | 14 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 14 |