E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Recurrent gastrointestinal and ovarian cancer |
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E.1.1.1 | Medical condition in easily understood language |
Recurrent gastrointestinal and ovarian 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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068069 |
E.1.2 | Term | Peritoneal carcinomatosis |
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 |
To study the safety and efficacy of IV Taxol combined with repeated pressurized intraperitoneal aerosol therapy (PIPAC) using albumin bound nanoparticle paclitaxel (nab-pac, Abraxane) in a multicentre, multinational phase I/II trial. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Phase I study: patients with advanced carcinomatosis from ovarian, gastric, or pancreatic origin. No alternative systemic treatment options are available.
- Phase II study: platinum resistant or refractory recurrent ovarian cancer or primary peritoneal carcinoma, FIGO stage IIIB or C.
- Selected stage IV patients with very limited metastatic disease are eligible for inclusion
- Age over 18 years
- Adequate performance status (Karnofsky index > 60%)
- Absence of intestinal or urinary obstruction
- Limited size of the majority of peritoneal tumor implants (< 5 mm)
- Absent or limited ascites
- Ability to understand the proposed treatment protocol and provide informed consent
- Expected life expectancy more than 6 months
- Laboratory data
o Serum creatinine ≤ 1.5 mg/dl or a calculated GFR (CKD-EPI) ≥ 60 mL/min/1.73 m2
o Serum total bilirubin ≤ 1.5 mg/dl, except for known Gilbert’s disease
o Platelet count > 100.000/µl
o Hemoglobin > 9g/dl
o Neutrophil granulocytes > 1.500/ml
o International Normalized Ratio (INR) ≤ 2
- Absence of alcohol and/or drug abuse
- No other concurrent malignant disease
- Written informed consent |
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E.4 | Principal exclusion criteria |
- Pregnancy or breast feeding. Women who can become pregnant must ensure effective contraception.
- Active bacterial, viral or fungal infection
- Active gastro-duodenal ulcer
- Parenchymal liver disease (any stage cirrhosis)
- Uncontrolled diabetes mellitus
- Psychiatric pathology affecting comprehension and judgement faculty
- General or local (abdominal) contra-indications for laparoscopic surgery
- Documented intolerance or allergy to paclitaxel (Taxol or Abraxane) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I: Maximally tolerated dose of Abraxane, administered every four weeks using intraperitoneal laparoscopy-assisted aerosolisation (PIPAC).
Phase II: Progression free survival, measured from the day of randomization. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I: after every study drug administration
Phase II: from the day of randomization until the end of study |
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E.5.2 | Secondary end point(s) |
Phase I:
- Surgical morbidity and mortality of laparoscopy
- Technical failure rate
- Pathological response rate
- Pharmacokinetic/Pharmacodynamic analysis
- Quality of life at 3,6,9, and 12 months
Phase II:
- Surgical morbidity and mortality of laparoscopy
- Technical failure rate
- Pathological response rate
- Overall survival
- Disease free survival |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- All endpoints: after each visit until end of study
- Quality of life at 3, 6, 9, and 12 months after first study drug administration |
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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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 |
Belgium |
Denmark |
France |
Germany |
Italy |
Switzerland |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | |
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 | 4 |