| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| patients with planned Paclitaxel chemotherapy due to ovarian or breast cancer |
| Patienten mit geplanter Paclitaxel-Chemotherapie aufgrund von Eierstock- oder Brustkrebs |
|
| E.1.1.1 | Medical condition in easily understood language |
| patients with planned Paclitaxel chemotherapy due to ovarian or breast cancer |
| Patienten mit geplanter Paclitaxel-Chemotherapie aufgrund von Eierstock- oder Brustkrebs |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10077974 |
| E.1.2 | Term | Peripheral neuropathic pain |
| E.1.2 | System Organ Class | 100000004852 |
|
| 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 demonstrate efficacy of Telmisartan to prevent new onset of PIPNP in patients requiring Paclitaxel chemotherapy due to ovarian or breast cancer until W12, assessed by the DN4 questionnaire |
|
| E.2.2 | Secondary objectives of the trial |
Incidence of PIPNP and comparison to available study data and the literature
Assessment of pain intensity, pain pattern and pain quality and their change over the 12 weeks by the PainDetect questionnaire and patient global pain visual analogue scale (VAS-Pain)
Determination of the cumulative incidence of neuropathic pain over 12 weeks
Assessment of quality of life and its change over 12 weeks by the FACT/GOG-NTX questionnaire
Quantification of the incidence of Paclitaxel-associated acute pain syndrome (PAPS)
Determination of the proportion of patients with need of PIPNP symptomatic therapy
Assessment of frequency, severity and relatedness of adverse events
explorative: Lipid profile analysis, Assessment of QST profile, Correlation of new onset of PIPNP and pain intensity with lipid profile and QST, Efficacy and safety comparison of different telmisartan doses on incidence and severity of PIPNP symptoms Comparison of PIPNP incidence to available study data and the literature
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
• Patients with a diagnosis of ovarian or breast cancer who are clinically eligible for Paclitaxel therapy and for whom Paclitaxel chemotherapy is planned (with use of standard treatment) in clinical routine care.
• Female patients ≥ 18 years and ≤ 80 years
• The patient must have completed radiotherapy or surgery for CNS metastases > 2 weeks prior to SCR. Patients must be neurologically stable, having no new neurological deficits on clinical examination, and no new findings on CNS imaging as documented in clinical routine care. If patients require steroids for management of CNS metastases, they must have been on a stable dose of steroids for 2 weeks preceding SCR.
• Written informed consent obtained prior to the initiation of any protocol-required procedures
• Willingness to comply to study procedures and study protocol
|
|
| E.4 | Principal exclusion criteria |
• Previously diagnosed or current peripheral neuropathic pain
• Other severe pain that might impair the assessment of neuropathic pain
• DN4 score ≥ 4
• Previous chemotherapy (incl. Paclitaxel) within the last 5 years (treatment with cyclophosphamide and an anthracycline as part of an ongoing adjuvant or neo-adjuvant regimen is allowed)
• Current or planned combinational chemotherapy-regimens, e.g., with platinum-based drugs (Her2 antibodies are allowed; Paclitaxel combination with Trastuzumab +/- Pertuzumab is allowed)
• All primary central nervous system (CNS) tumors or symptomatic CNS metastases that are neurologically unstable (Note: Only patients with controlled CNS metastases may participate in this trial)
• Previously reported intolerance to AT1-receptor-blockers
• Hypotension (blood pressure < 110/70 mmHg) median from 3 measurements; start of measurement after patients has been seated for at least 5 min)
• Current intake of Aliskiren, Digoxin or ACE-inhibitors at BL (treatment change from ACE-inhibitors to Telmisartan is allowed, with treatment start of Telmisartan at BL)
• Current intake of antidepressants (e.g., Amitriptylin), antiepileptics (e.g., Gabapentin, Pregabalin, Lamotrigine), Duloxetine, Glutamin, Vitamin E
• Current intake of Telmisartan at SCR
• Insufficient hepatic or renal function at SCR:
o Serum creatinine ≥ 1.5 x upper limit of normal (ULN)
o Total bilirubin > 1.5 x ULN
o GOT/GPT ≥ 3 x ULN or >5 in case of documented liver metastasis
• Impairment of GI function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• History of or current severe psychological illness or condition
• Uncontrolled coronary angina or symptomatic congestive heart failure (NYHA Class III or IV)
• Patients with current malignant disease, other than that being treated in this study. Exceptions to this exclusion criterion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to SCR; completely resected basal cell and squamous cell skin cancers; and completely resected carcinoma in situ of any type
• Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient`s safety and of the study outcome
• History of or evidence of current active Hepatitis B or C or HIV infection with documentation not older than 8 weeks (due to blood sample processing for lipid profile analysis)
• Known hypersensitivity to any component of the IMP
• Women lactating, pregnant, nursing or of childbearing potential with a positive pregnancy test
• Females of reproductive potential not willing to use highly effective contraception (non-hormonal contraceptive method with a failure rate of < 1% per year, or combination of two effective non-hormonal contraceptive methods, e.g. barrier method and spermicide)
• Alcohol, drug or chemical abuse
• Current participation in another interventional clinical trial or participation within the last 90 days
• Underage or incapable patients
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| • Proportion of patients with absence of PIPNP at W12 characterized by DN4 score: DN4 < 4 (DN4 Score 0-10) |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| The DN4 score will be assessed at baseline and week 12 |
|
| E.5.2 | Secondary end point(s) |
• Proportion of patients with new onset of PIPNP at all visits, assessed using the DN4 questionnaire (DN4 ≥ 4) and comparison to available study data and the literature
• DN4 and change to BL
• PainDetect score and change to BL
• VAS-Pain score and change to BL
• Incidence of neuropathic pain (as determined by the treating physician)
• FACT/GOG-NTX score and change to BL (QoL)
• Incidence of Paclitaxel-associated acute pain syndrome (PAPS)
• Proportion of patients in need of PIPNP symtomatic therapy (as decided by the treating physician)
Explorative variables:
• Lipid profile analysis before and after Telmisartan and Paclitaxel start
• Assessment of QST profile at selected visits
• Correlation of new onset of PIPNP and pain intensity with lipid profile and QST result
• Efficacy and safety comparison of different telmisartan doses (adaption to a daily dose of 60 mg/day will be allowed if 80 mg/day is not tolerated) on incidence and severity of PIPNP symptoms
Safety:
• Frequency, type, severity and relatedness of adverse events (according to CTCAE version 4.0)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
baseline, week 2, week 4, week 7, week 10 and week 12
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| 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 | Yes |
| 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
|
| time point of study closure of all sites |
|
| 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 | 5 |
| 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 | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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