E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pancreatic ductal adenocarcinoma |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 3.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033602 |
E.1.2 | Term | Pancreatic Adenocarcinoma resectable |
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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 |
1. To study the effect of GDC-0449 treatment on the stromal cell and tumour cell hedgehog signalling strength in patients with pancreatic ductal adenocarcinoma.
2. To study the safety and tolerability of pre-operative GDC-0449 treatment in patients that undergo Whipple’s surgery for pancreatic ductal adenocarcinoma.
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E.2.2 | Secondary objectives of the trial |
1. To study the effect of GDC-0449 treatment on stromal architecture in patients with PDAC.
2. To evaluate GDC-0449 tissue and plasma concentrations in patients with PDAC.
3. To study the treatment effect of GDC-0449 on the perfusion and elasticity of the tumour in patients with PDAC.
4. To study the treatment effect of GDC-0449 on circulating biomarkers of PDAC.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Documented tissue diagnosis of pancreatic ductal adenocarcinoma with a sufficient amount of tissue for Laser Capture Micro-dissection (LCM) of the stromal and tumour compartments.
2. Confirmed eligibility for Whipple’s procedure by Multi-Disciplinary Team (MDT) and surgeon review.
3. Adequate organ function defined as: •Creatinine clearance ≥ 60ml/min (as defined by Cockroft-Goult) •Electrolytes (Na/K/Ca) within institutional normal limits •ALT/AST <5*ULN •PTT<2*ULN, prior supplementation with vitamin K is allowed •Adequate blood counts: neutrophils >1,500/μl, Hb > 6 mmol/L, platelets >100.000/μl •Albumin > 30mg/dL
4. Written informed consent
5. Male or female aged 18 years or over.
6. WHO performance status 0-1
7. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
8. Males should not donate sperm during treatment or up to 3 months after the last dose. Contraception is required for men during the trial, and for 3 months after the last dose.
9. Women of childbearing potential are required to have a negative serum pregnancy test (with sensitivity of at least 25 mIU/mL) within 10−14 days and within 24 hours prior to the first dose of GDC-0449. Contraception is required 4 weeks before the trial, during the trial, and for 12 months after the last dose.
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E.4 | Principal exclusion criteria |
1. Known Hepatitis B/C or HIV infection
2. Known hypersensitivity to GDC-0449
3. Active cardiac ischemic disease (this criterion only applies for participation in the imaging part of the study)
4. Women, who are pregnant, plan to become pregnant or are lactating (during the study or for up to 12 months after the last dose).
5. Concurrent participation in another clinical trial using an investigational medicinal product.
6. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or in the judgment of the investigator would make it undesirable for the patient to enter the trial (i.e. patients is not able to swallow tablets).
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Extent of gli signalling inhibition (gli signalling reflects the activity of the hedgehog signalling pathway) as measured by qRT-PCR of gli in microdissected stromal tissue derived from biopsies and surgical material.
2. Toxicity as measured by: post-operative mortality, post-operative pancreatic leakage and any unexpected excess complications after surgery and adverse events during treatment and post-operatively as defined by NCI CTCAE v3.0.
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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 | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | Information not present in EudraCT |
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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End of Trial is defined as the time at which all patients enrolled in the study have completed study treatment and all procedures up to and including day of surgery +29 days. |
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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 | 1 |
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 | 1 |
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 |