E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Locally advanced unresectable pancreatic adenocarcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced Pancreatic Cancer |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033606 |
E.1.2 | Term | Pancreatic cancer non-resectable |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of the trial is to evaluate efficacy, as measured by overall survival (OS), of gemcitabine in combination with TH-302 compared to gemcitabine in
combination with placebo in subjects with previously untreated locally advanced unresectable or metastatic pancreatic adenocarcinoma. |
|
E.2.2 | Secondary objectives of the trial |
To assess efficacy with resepct to:
progression free survival (PFS), and
objective response (OR) and disease control.
To assess patient reported outcomes (PROs) with respect to quality of life (QoL) measured with EORTC QLQ-C30 (Version 3) and EQ-5D-5L, and pain measured by a Numerical Rating Scale (NRS).
To investigate levels of carbohydrate antigen 19-9 (CA19-9),
To assess the safety and tolerability of gemcitabine in combination with TH-302 compared with gemcitabine in combination with placebo. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- At least 18 years of age.
- Locally advanced unresectable or metastatic pancreatic ductal adenocarcinoma proven by
histology or cytology and previously untreated with chemotherapy or systemic therapy
- Measurable disease (at least one target lesion outside of previous radiation fields) or
non-measurable disease by RECIST 1.1 criteria (see Appendix III).
- Documentation of disease progression since any prior therapy.
- Life expectancy of at least 3 months.
- Acceptable liver function.
- Acceptable renal function.
- Acceptable hematologic status.
- Other protocol defined inclusion criteria may applied |
|
E.4 | Principal exclusion criteria |
1. New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial
infarction within 6 months prior to the date of randomization, unstable arrhythmia or
symptomatic peripheral arterial vascular disease.
2. Symptomatic ischemic heart disease.
3. Known brain, leptomeningeal or epidural metastases (unless treated and well controlled for at
least 3 months).
4. Previous malignancy other than pancreatic cancer in the last 5 years, except for adequately
treated non-melanoma skin cancer or pre-invasive cancer of the cervix.
5. Severe chronic obstructive or other pulmonary disease with hypoxemia
6. Major surgery, other than diagnostic surgery, ≤28 days prior to the date of randomization.
Subject must have completely recovered from surgery.
7. Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy.
8. Treatment of pancreatic cancer with radiation therapy or surgery ≤28 days prior to the date of
randomization.
9. Prior therapy with a hypoxic cytotoxin.
10. Subjects who participated in an investigational drug or device trial ≤28 days prior to Day 1 of
the first cycle.
11. Known infection with HIV, or an active infection with hepatitis B or hepatitis C.
12. Subjects who have exhibited allergic reactions to a structural compound similar to TH-302 or
the drug product excipients or to gemcitabine or its excipients.
13. Other protocol defined exclusion criteria may applied. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is Overall Survival (OS) time. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
OS will be evaluated when 508 events (deaths) of randomized patients are reported. |
|
E.5.2 | Secondary end point(s) |
- Progression-freee Survival (PFS) Time.
- Best Overall Respose Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
- Disease control Rate according to Response Evaluation Criteria in solid Tumors (RECIST) version 1.1.
- Quality of Life (QOL) EuroQuol-5D (EG-5D) Health Outcome questionnaire.
- Pain intensitiy using a visual analogue scale (VAS).
- Serum CA 19-9 response rate.
- Number of participants with treatment-emergent adverse events (TEAE) graded according to National Cancer Institute Common Terminology Criteria for Adverse Eents (NCI CTCAE v.4.03). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints will be evaluated at the same timepoint as OS data is mature. |
|
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 | No |
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) | 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 | 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 | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
|
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 125 |
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 |
Austria |
Belgium |
Bulgaria |
Canada |
Czech Republic |
European Union |
Finland |
France |
Germany |
Hungary |
Israel |
Italy |
Netherlands |
Poland |
Romania |
Russian Federation |
Slovakia |
South Africa |
Spain |
Ukraine |
United Kingdom |
United States |
|
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
|
Once the event-driven unblinding and final analysis is complete (unblinding and final analysis occurs after 508 events [deaths]), the Sponsor will initiate activities towards execution of an extension protocol, if appropriate, based on study outcomes, so that this Phase III study can be closed. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |