| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Squamous Cell Carcinoma of the Head and Neck |
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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 | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10060121 |
| E.1.2 | Term | Squamous cell carcinoma of head and neck |
| E.1.2 | System Organ Class | 100000004864 |
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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 |
| Compare overall survival for the treatment regimens in the entire study population, in the subgroup of patients with recurrent loco-regional disease (with or without metastases) and in the subgroup of patients with metastatic disease without measured local recurrence at time of randomization. |
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| E.2.2 | Secondary objectives of the trial |
Secondary:
(1) Compare progression free survival for the treatment regimens in the entire study population, in the subgroup of patients with recurrent loco-regional disease (with or without metastases) and in the subgroup of patients with metastatic disease without measured local recurrence at time of randomization.
(2) Compare Objective Response (Complete Response (CR) + Partial Response (PR)) rate and Clinical Benefit Rate (CR + PR + Stable Disease (SD)) and duration of response for the treatment regimens in the entire study population, in the subgroups as described above.
(3) Compare the safety and tolerability of the treatment regimens in the study population.
Tertiary:
Compare Best % Tumor Specific Response in loco-regional disease and metastatic disease for the treatment regimens in the entire study population, in the subgroups as described above.
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Have recurrent or metastatic (R/M) histologically confirmed squamous cell carcinoma (SCC) of the head and neck (oropharynx, oral cavity, larynx, hypopharynx) or squamous cell nasopharynx cancer (NPC) with distal metastasis(es) and no secondary cancers.
Note: Patients with NPC without distal metastasis(es) or with undifferentiated NPC are NOT eligible.
2. Have at least one lesion that is measurable by computed tomography (CT) or magnetic resonance imaging (MRI). (Lesions persisting in previously treated radiation fields are considered NOT evaluable for response. Lesions in previous radiation fields are considered evaluable for response if representing a relapse in a mucosal or nodal lesion that previously demonstrated a complete response. Any new lesion within the previous radiation fields is acceptable for determination of response and/or progression).
3. Have completed first line chemotherapy for R/M SCCHN which progressed on or within 190 days following the completion of platinum or platinum-based chemotherapy (including platinum/cetuximab regimens if approved and/or available for the patient).
4. Have NO continuing acute toxic effects (except alopecia) of any prior radiotherapy, chemotherapy, or surgical procedures, i.e., all such effects must have resolved to Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade ≤ 1. Any surgery involving the SCC for which the patient is being treated (except biopsies) must have occurred at least 28 days prior to study enrollment.
5. Be at least 18 years of age.
6. Have received NO chemotherapy, radiotherapy, immunotherapy or hormonal therapy within 28 days prior to receiving study drug.
7. Have an ECOG Performance Score of ≤ 2.
8. Have a life expectancy of at least 3 months.
9. Have baseline laboratory results as follows:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109 [SI unit 109/L]
• Platelets ≥ 100 x109 [SI units 109/L] (without platelet transfusion)
• Hemoglobin ≥ 9.0 g/dL [SI units gm/L] (with or without RBC transfusion)
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN)
• Bilirubin ≤ 1.5 x ULN
• AST/ALT ≤ 2.5 x ULN
• Negative pregnancy test for females with childbearing potential.
10. Have signed an informed consent indicating that the patient is aware of the neoplastic nature of their disease and has been informed of the procedures of the protocol, the experimental nature of the therapy, alternatives, potential benefits, side effects, risks, and discomforts.
11. Be willing and able to comply with scheduled visits, the treatment plan, and laboratory tests.
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| E.4 | Principal exclusion criteria |
1. Receive concurrent therapy with any other investigational anticancer agent while on study.
2. Have been treated with a taxane for SCCHN.
3. Have current -- or with a history of -- brain metastases because of their poor prognosis and because of the frequent development of progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
4. Be on chronic immunosuppressive therapy or have known HIV infection or active hepatitis B or C.
5. Be a pregnant or breast-feeding woman. Female patients of childbearing potential must agree to use effective contraception, be surgically sterile, or be postmenopausal. Male patients must agree to use effective contraception or be surgically sterile. Barrier methods are a recommended form of contraception.
6. Have clinically significant cardiac disease (New York Heart Association, Class III or IV) including, but not limited to, pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year prior to study entry.
7. Have dementia or any altered mental status that would prohibit informed consent.
8. Have any other acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Principal Investigator, would make the patient inappropriate for this study.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| OS will be measured from the date of randomization to the date of death from any cause. Patients who are still alive or who are deemed lost to follow-up at the date of their last office visit or last phone contact, will be censored. |
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| E.5.2 | Secondary end point(s) |
1. Tumour Evaluation assessed by CT or MRI following the revised RECIST Guidelines version 1.1.
2. Tumour Biopsy: At some selected study sites, patients whose tumors are assessible to biopsy will be asked to undergo tumour biopsy (baseline and post therapy) to evaluate Ras pathway status, HPV status and to measure viral replication within the tumour.
3. Progression Free Survival (PFS).
4. Objective Response and Clinical Benefit Rate.
5. % tumor specific responses (tertiary endpoint).
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Tumour evaluation every 6 weeks on and after study until disease progression, study termination, initiation of subsequent anticancer therapy, death, loss to follow-up or withdrawal of consent.
2. Tumour biopsy: Timing will vary, based on response, in order to optimise the data generated by this assessment.
3. PFS will be measured from the date of randomization to the date of disease progression as defined by RECIST 1.1 or death from any cause. Patients’ PFS times will be censored at the date of their last office visit if they are alive and have not experienced disease progression, or if they are deemed lost to follow-up.
4. See tumour evaluation.
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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 | Yes |
| 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) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| 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) | No |
| E.8.2.2 | Placebo | Yes |
| 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 | 1 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 40 |
| 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 |
| Canada |
| Russian Federation |
| United States |
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| 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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| Patients may continue to receive study combination therapy for up to 8 cycles and thereafter blinded placebo or blinded REOLYSIN® until the patient has progressive disease or meets other criteria for removal from study as defined in the protocol |
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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 | 6 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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