| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic Pancreatic Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 18.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10033605 |
| E.1.2 | Term | Pancreatic cancer 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 evaluate the efficacy of ACP-196 and nab-paclitaxel/gemcitabine based on ORR in subjects with metastatic pancreatic cancer using standard response criteria |
|
| E.2.2 | Secondary objectives of the trial |
| To characterize the safety profile of ACP-196 and nab-paclitaxel/gemcitabine in subjects with metastatic pancreatic cancer |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Men and women ≥ 18 years of age.
2) ECOG performance status of 0 or 1.
3) Histologically or cytologically confirmed metastatic adenocarcinoma of the pancreas.
4) Presence of radiographically measurable disease per RECIST 1.1. guidelines.
5) No previous radiotherapy, chemotherapy or investigational therapy for the treatment of metastatic disease. Prior treatment with 5-FU or gemcitabine administered as a radiation sensitizer in the adjuvant setting is allowed, provided at least 6 months have elapsed since completion of the last dose and no lingering
toxicities are present.
6) Women who are sexually active and can bear children must agree to use
highly effective forms of contraception during the study and for 90 days after the last
dose of ACP-196 or 4 months after the last dose of nab-paclitaxel/gemcitabine,
whichever is longer. Highly effective forms of contraception are defined in protocol section 3.10.4.
7) Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study and for 90 days after the last dose of ACP-196 or 4 months after the last dose of nab-paclitaxel/gemcitabine, whichever is longer. Highly effective forms of contraception are defined in protocol section 3.10.4.
8) Men must agree to refrain from sperm donation during the study and for 90 days after the last dose of ACP-196 or 4 months after the last dose of nab-paclitaxel/gemcitabine, whichever is longer.
9) Willing and able to participate in all required evaluations and procedures in this
study protocol including swallowing capsules without difficulty
10) Ability to understand the purpose and risks of the study and provide signed and
dated informed consent and authorization to use protected health information (in
accordance with national and local subject privacy regulations) |
|
| E.4 | Principal exclusion criteria |
1) Prior malignancy (other than pancreatic cancer), except for adequately treated
basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer
from which the subject has been disease free for ≥ 2 years . Note: These cases must be discussed with the medical monitor.
2) Known CNS metastases and/or carcinomatous meningitis.
3) Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
screening, any Class 3 or 4 cardiac disease as defined by the New York Heart
Association Functional Classification, or QTc > 480 msec at screening.
4) Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass. Note: Subjects with prior pancreatoduodenectomy are not excluded.
5) Biliary obstruction or presence of a percutaneous biliary drain. Note: Subjects
with endobiliary stents may participate as long the enrollment criterion relating to
serum bilirubin concentration is met.
6) Prior therapy with any inhibitor of Btk, Akt, Jak, mTOR, PI3K, or Syk.
7) History of interstitial lung disease or active non-infectious pneumonitis.
8) History of bleeding diathesis (eg, hemophilia or von Willebrand disease).
9) Major surgical procedure within 28 days of first dose of study drug.
10) Known hypersensitivity to gemcitabine or nab-paclitaxel.
11) Requires treatment with a proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
12) Requires treatment with a strong CYP3A4 or CYP2C8 inhibitor/inducer.
13) Requires or receiving anticoagulation with warfarin or equivalent vitamin K
antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
14) Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids. Note: At screening and during study participation, subjects may
use topical or inhaled corticosteroids or systemic corticosteroids at dosages equivalent to prednisone ≤ 10 mg/day as therapy for comorbid conditions.
15) Known history of HIV or active infection with HCV or HBV or any active infection requiring systemic therapy with 14 days of randomization.
16) History of stroke or intracranial hemorrhage within 6 months before the first dose of study drug.
17) ANC < 1.5 x 109/L or platelet count < 100 x 109/L or hemoglobin < 9.0 g/dL.
18) Total bilirubin > ULN; and AST or ALT > 3.0 x ULN.
19) PT and aPTT > 1.2 x the ULN.
20) Estimated creatinine clearance of < 30 mL/min, calculated using the formula of
Cockcroft and Gault (140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female.
21) Breastfeeding or pregnant.
22) Concurrent participation in another therapeutic clinical trial.
23) Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall response rate (ORR) is the primary efficacy endpoint. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Tumor assessments will be performed per the protocol-defined schedule: at screening, then on Day 1 of every other cycle starting with Cycle 3 (eg, Cycle 3 Day 1, Cycle 5 Day 1, etc.) |
|
| E.5.2 | Secondary end point(s) |
In addition, the following efficacy endpoints will be evaluated:
Duration of response (DOR), progression-free survival (PFS), and overall survival (OS)
|
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| DOR and PFS will be evaluated per the same tumor assessment schedule as described for ORR (per the protocol). In addition to the protocol-defined visits, subjects will be followed for OS every 12 weeks after study treatment discontinuation. |
|
| 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 | Yes |
| 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) | 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 | Yes |
| 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
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 56 |
| 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 |
| Germany |
| Spain |
| 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
|
Treatment can continue until the end of trial, defined as 52 weeks (13 cycles) after the last subject is randomized to the study, for subjects who are tolerating therapy and not progressing. Subjects who have confirmed progressive disease will discontinue study treatment.
|
|
| 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 | 10 |
| 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 | 3 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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