E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced solid malignancies |
Gevorderde solide tumoren |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced solid types of cancer |
Gevorderde solide vormen van kanker |
|
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 | 19.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10029104 |
E.1.2 | Term | Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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 determine the safety of extended use treatment with weekly ModraDoc006/r available for patients who completed treatment in one of the phase I trials with ModraDoc006/r, who might have clinical benefit of continued treatment with the oral docetaxel formulation. |
De veiligheid van voortgaande behandeling met wekelijks ModraDoc006/r onderzoeken, beschikbaar voor patienten die behandeling in een voorafgaande fase 1 studie met ModraDoc006/r hebben afgerond en mogelijk klinisch voordeel hebben van gecontinueerde behandeling met deze orale docetaxel formulering. |
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E.2.2 | Secondary objectives of the trial |
not applicable |
niet van toepassing |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Histological or cytological proof of cancer
2. Patients who might benefit from a weekly (oral) docetaxel regime as judged by the treating oncologist.
3. Patients who received treatment with ModraDoc006/r with acceptable safety (as judged by the PI; for criteria see below in section 3 of inegibility criteria) in phase I trials with ModraDoc006/r, including (but not limited to) the N15FED (food-interaction study), N16AED (absorption-excretion study), N16DOL (normal or impaired liver function). A maximum delay of 21 days between the last dose in the previous phase I trial and the first dose in the N17DEX is allowed.
4. Age ≥ 18 years
5. WHO performance status of 0, 1 or 2;
6. Minimal acceptable laboratory values defined as:
a. ANC of ≥ 1.5 x 109 /L
b. Platelet count of ≥ 100 x 109 /L
c. Renal function as defined by serum creatinine equal or lower than 3.0 x ULN
d. Hepatic function as defined by serum bilirubin equal or lower than 5.0 x ULN, ALAT and ASAT equal or lower than 5.0 x ULN, except for patients who have been treated in the N16DOL study.
7. Negative pregnancy test (urine/serum) for female patients with childbearing potential, assessed at the screeningsvisit for the previous phase I trial with ModraDoc006/r treatment
8. Able and willing to swallow oral medication
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1. Histologisch of cytologisch bewezen maligniteit
2. Patienten die baat kunnen hebben van een wekelijkse behandeling met oraal docetaxel, als beoordeeld door de behandeled oncoloog
3. Patienten die behandeld zijn met acceptabele veiligheid met ModraDoc006/r (als beoordeeld door de PI; voor criteria zie sectie 3 van de exclusie criteria) in een voorafgaande fase I trial met ModraDoc006/r, inclusief (maar niet gelimiteerd tot) de N15FED (voedsel-interactie studie), N16AED (absorptie-excretie studie), N16DOL (normale or verminderde lever functie). Tussen de laatste dosis van ModraDoc006/r in de voorafgaande fase I trial en de startdosis van de N17DEX is uitstel tot maximaal 21 dagen toegestaan.
4. Leeftijd gelijk aan of hoger dan 18 jaar
5. WHO performance status van 0, 1 of 2;
6. Minimale acceptabele laboratorium waarden:
a. ANC ≥ 1.5 x 109 /L
b. Trombocyten ≥ 100 x 109 /L
c. Renale functie gedefinieerd als serum creatinine gelijk aan of lager dan 3.0 x ULN
d. Hepatische functie gedefinieerd als serum bilirubine gelijk aan of lager dan 5.0 x ULN, ALAT en ASAT gelijk aan of lager dan 5.0 x ULN, behalve voor patienten die zijn behandeld in de N16DOL studie.
7. Negatieve zwangerschapstest (urine/serum) voor vrouwelijke patienten met de potentie om zwanger te worden, bij voorkeur afgenomen bij de screeningsafspraak van de voorafgaande fase I studie met ModraDoc006/r behandeling.
8. Bereid en in staat tot inname van orale medicatie |
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E.4 | Principal exclusion criteria |
1. Concomitant use of MDR and CYP3A modulating drugs such as Ca+-entry blockers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol and grapefruit juice, concomitant use of HIV medications; other protease inhibitors, (non) nucleoside analoga, St. Johns wort or macrolide antibiotics.
2. Symptomatic brain metastases or leptomeningeal metastases. Patients with brain metastases are allowed if they received adequate treatment, are asymptomatic in the absence of corticosteroid therapy and anticonvulsant therapy for at least 6 weeks. Radiotherapy for brain metastases must have been completed at least 4 weeks prior to start of study treatment.
3. Clinically significant safety issues during previous therapy with ModraDoc006/r as judged by the PI, which cannot be solved by dose reduction and/or treatment delay.
4. Unreliable contraceptive methods. Both men and women using ModraDoc006/r must agree to use a reliable contraceptive method throughout the treatment
5. Oncolytic therapy or any treatment with investigational drugs other than ModraDoc006/r between the completion of the phase I trial with ModraDoc006/r and the start of extended use of ModraDoc006/r Palliative limited radiation is allowed, but must have been completed at least 4 weeks prior to start of extended use. |
1. Gelijktijdig gebruik van MDR en CYP3A modulerende medicatie zoals Ca+ blokkers (verapamil, dihydropyridines), cyclosporine, quinidine, quinine, tamoxifen, megestrol en grapefruit juice, HIV medicatie; andere protease inhibitors, (non) nucleoside analoga, St. Janskruid of macrolide antibiotica.
2. Symptomatische hersen metastasen of leptomeningeale metastasering. Patients with hersen metastasering mogen deelnemen aan de studie als zij adequate behandeling hebben gehad, asymptomatisch zijn zonder gebruik van corticosteroïden of anti-epileptica voor minstens 6 weken. Radiotherapie voor hersenmetastasen moet zijn afgerond voor minstens 4 weken voorafgaand aan start van de studie.
3. klinisch significante veiligheidsproblemen gedurende de voorafgaande behandeling met ModraDoc006/r als beoordeeld door de PI, welke niet opgelost kunnen worden door dosisreductie en/of uitstel van de behandeling.
4. Onbetrouwbare anticonceptie methoden. Zowel mannen als vrouwen die behandeld worden met ModraDoc006/r moeten instemmen met het gebruik van adequate anticonceptie gedurende de behandeling.
5. Oncolytische therapie of elke experimentele behandeling met anders dan met ModraDoc006/r tussen afronding van de voorafgaande fase I trial met ModraDoc006/r en de start van ModraDoc006/r in de N17DEX. Palliatieve bestraling is toegestaan, maar moet minstens 4 weken voor start van de N17DEX zijn afgerond. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The safety of extended use treatment with weekly ModraDoc006/r available for patients who completed treatment in one of the phase I trials with ModraDoc006/r, who might have clinical benefit of continued treatment with the oral docetaxel formulation. |
De veiligheid van voortgaande behandeling met wekelijks ModraDoc006/r, beschikbaar voor patienten die behandeling in een voorafgaande fase 1 studie met ModraDoc006/r hebben afgerond en mogelijk klinisch voordeel hebben van gecontinueerde behandeling met deze orale docetaxel formulering. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Ongoing evaluation during the complete duration of the study |
Evaluatie gebeurt continu gedurende de gehele behandeling |
|
E.5.2 | Secondary end point(s) |
Not applicable |
Niet van toepassing |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Not applicable |
Niet van toepassing |
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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 | 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 | 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) | 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
| 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
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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 | |
E.8.9.2 | In all countries concerned by the trial years | 3 |