E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Metastatic Pancreatic Adenocarcinoma |
|
E.1.1.1 | Medical condition in easily understood language |
Metastatic 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 | 15.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033599 |
E.1.2 | Term | Pancreatic adenocarcinoma metastatic |
E.1.2 | System Organ Class | 100000004864 |
|
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 compare the additive efficacy of GS-6624 vs. placebo in combination
with gemcitabine as measured by improvement in progression free
survival (PFS) |
|
E.2.2 | Secondary objectives of the trial |
To compare the additive efficacy of GS-6624 vs. placebo in combination
with gemcitabine as measured by
• Overall Survival (OS)
• Objective response rate (by modified RECIST version 1.1) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Willingness to sign the subject informed consent
2. Initial diagnosis of metastatic pancreatic cancer must have occurred ≤ 6 weeks
prior to the completion of screening
3. The presence of measurable metastatic pancreatic cancer documented
by contrast enhanced CT (or MRI) scan in addition to 1 of the
following:
a) Histological diagnosis of pancreatic adenocarcinoma confirmed by
pathologist OR
b) Pathologist confirmed histological/cytological diagnosis of
adenocarcinoma consistent with pancreatic origin in conjunction with
either:
(1) The presence of a mass in the pancreas OR
(2) A history of resected pancreatic carcinoma
4. Measurable disease per RECIST (ver. 1.1), defined with all of
following criteria:
a) Lesions accurately measured in at least 1 dimension
b) The longest diameter in the plane of measurement is to be recorded
c) A minimum size of 10 mm if CT slice thickness ≤ 5 mm; if
thickness is > 5 mm then the minimum size of measurable lesions
should be twice slice thickness
5. Male or female ≥18 years of age
6. ECOG Performance Status of 0 or 1
7. Women of childbearing potential must agree to use 1 medically
approved (i.e., mechanical or pharmacological) contraceptive measure
and have their partners agree to an additional barrier method of
contraception for the duration of the study and for 90 days after the last
administration of study drug
8. Male subjects must agree to use protocol-recommended methods of contraception during heterosexual intercourse and avoid sperm donation for the duration of this study and for 6 months after the last dose of gemcitabine.
9. Adequate organ function defined as follows:
a) Hematological: Platelets ≥100 x 109/L; Hemoglobin ≥9.0 g/dL;
Absolute Neutrophil Count (ANC) ≥1.5 x 10^9/L
b) Hepatic: AST/ALT ≤2.5 x ULN (if liver metastases are present,
≤5 x ULN); Total or conjugated bilirubin ≤1.5 x ULN
c) Renal: Serum Creatinine ≤ 1.5 x ULN OR creatinine clearance ≥ 60 ml/minute as calculated by the Cockroft-Gault method
10. Coagulation: International Normalized Ratio (INR) ≤ 1.6 (unless receiving anticoagulation therapy). Patients on full dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin. If receiving warfarin, the patient must have an INR ≤ 3.0 and no active bleeding (ie, no bleeding within 14 days prior to first dose of study therapy). |
|
E.4 | Principal exclusion criteria |
1. A history or evidence of clinically significant disorder other than metastatic cancer of the pancreas or clinical significant laboratory finding that in the investigator’s judgment would pose a risk to subject safety, interfere with study procedures, or prevent completion of the study
2. A diagnosis of pancreatic islet neoplasms
3. Subject has undergone major surgery other than diagnosis surgery within 4 weeks of enrollment (Part A)/ randomization (Part B)
4. Subjects for whom combination treatment with erlotinib and gemcitabine was planned
5. Subjects with biliary obstruction requiring external drainage
6. Pregnant or lactating
7. Known or suspected cerebral metastases
8. History or presence of any form of cancer, other than metastatic pancreatic cancer, within the 3 years prior to enrollment, with the exception of excised basal cell or squamous cell carcinoma of the skin, stage 0 or 1 melanoma, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis
9. Unstable cardiovascular function including but not limited to: myocardial infarction within the last 6 months of screening, symptomatic congestive heart failure (New York Heart Association Classification > Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
10. Uncontrolled hypertension (seated systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) at Screening.
11. Clinically active liver disease, including active viral hepatitis (HBV or HCV) or cirrhosis
12. Known HIV infection
13. Systemic fungal, bacterial, viral, or other infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement) despite appropriate antibiotics use
14. Prior or concurrent anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy) for the treatment of inoperable locally advanced or metastatic pancreatic cancer; prior radiotherapy and chemotherapy given as pre-operative neoadjuvant therapy or radio sensitizers for locally advanced pancreatic cancer are allowed
15. Participation in an investigational drug or device trial with therapeutic intent within 30 days prior to study Day 1 of Cycle 1 or within 5 times the half-life of the investigational drug in the other clinical study, if known, whichever is shorter
16. Known hypersensitivity to the study investigational medicinal products or formulation excipients
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression free survival |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Progression free survival is the primary endpoint is measured as time from
date of randomization to the earliest event time of a) death regardless of cause, or b) first
indication of disease progression. |
|
E.5.2 | Secondary end point(s) |
Overall Survival
Objective response rate (by modified RECIST version 1.1) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Overall survival is measured as time from date of randomization to death regardless of cause. |
|
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 | 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 | 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) | No |
E.8.2.2 | Placebo | Yes |
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
| 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 | 30 |
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 |
Germany |
Poland |
Russian Federation |
United States |
|
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 20 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 20 |
E.8.9.2 | In all countries concerned by the trial days | 0 |