| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Untreated Metastatic Pancreatic Ductal Adenocarcinoma |
|
| E.1.1.1 | Medical condition in easily understood language |
| Untreated cancer of the pancreas, arising from the duct cells within the pancreas and spreading to the lymphatic system and distant organs. |
|
| 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 | PT |
| E.1.2 | Classification code | 10073364 |
| E.1.2 | Term | Ductal adenocarcinoma of pancreas |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| 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 |
- Lead-in phase: To evaluate the safety, pharmacokinetics, and define the maximum tolerated dose (MTD) of momelotinib (MMB) combined with gemcitabine/nab-paclitaxel (nab-P+G) in subjects with previously untreated metastatic pancreatic ductal adenocarcinoma.
- Randomized treatment phase: To determine the efficacy of nab-P+G combined with either MMB or placebo in subjects with previously untreated metastatic pancreatic ductal adenocarcinoma as measured by improvement in overall survival (OS).
|
|
| E.2.2 | Secondary objectives of the trial |
Lead-in phase: To evaluate the efficacy of MMB combined with nab-P+G in subjects with previously untreated metastatic pancreatic ductal adenocarcinoma.
Randomized treatment phase:
- To evaluate the efficacy of nab-P+G combined with either MMB or placebo as measured by improvement in progression-free survival (PFS)
- To evaluate the efficacy of nab-P+G combined with either MMB or placebo as measured by improvement in overall response rate (ORR)
- To evaluate the safety and tolerability of nab-P+G combined with either MMB or placebo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1) Age ≥ 18 years old
2) Initial diagnosis of metastatic pancreatic adenocarcinoma must have occurred ≤ 6 weeks prior to enrollment
3) The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:
- Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically, OR
- Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin in conjunction with either:
- The presence of a mass in the pancreas, OR
- A history of resected pancreatic adenocarcinoma
4) Measurable disease per RECIST v1.1
5) Adequate organ function defined as follows:
- Hepatic: Total bilirubin < upper limit of normal (ULN); AST (SGOT) and ALT (SGPT) ≤ 3 x upper limit of normal (ULN)
- Hematological: Absolute neutrophil count (ANC) > 1500 cells/mm3, platelet > 100,000 cells/mm3, hemoglobin > 9 g/dL
- Renal: Serum creatinine < ULN OR calculated creatinine clearance (CrCl) ≥ 60 ml/min as calculated by the Cockroft-Gault method
6) Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
7) mGPS of 1 or 2 at Screening (randomized phase only)
8) Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years postmenopausal)
9) Male and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Appendix 3
10) Females who are nursing must agree to discontinue nursing before the first dose of investigational product (IP)
11) Able to comprehend and willing to sign the written informed consent form |
|
| E.4 | Principal exclusion criteria |
1) Neoadjuvant or adjuvant chemotherapy or chemoradiotherapy for pancreatic adenocarcinoma
2) Currently or previously treated with biologic, small molecule, immunotherapy, chemotherapy, or other agents for metastatic
pancreatic carcinoma
3) Uncontrolled intercurrent illness including, but not limited to, active uncontrolled infection, active or chronic bleeding event within 4 weeks prior to first dose of IP, uncontrolled cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements as judged by treating physician
4) History of a concurrent or second malignancy except for adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to enrollment, adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥ 5 years
5) Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (ie, larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy), within 28 days of first dose of IP
6) Minor surgical procedure(s) within 7 days of enrollment or not yet recovered from prior minor surgery (placement of central venous
access device, fine needle aspiration, or endoscopic biliary stent ≥ 1 day before enrollment is acceptable)
7) Known positive status for human immunodeficiency virus (HIV)
8) Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
9) Peripheral neuropathy ≥ Grade 2
10) Known or suspected brain or central nervous system metastases
11) Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (ie, lymphoma, sarcoma), adenocarcinoma originating from the biliary tree or cystadenocarcinoma
12) History of interstitial pneumonitis and/or require supplemental oxygen therapy
13) External biliary drain
14) Documented myocardial infarction or unstable/uncontrolled cardiac disease (ie, unstable angina, congestive heart failure [New York Heart Association > Class III]) within 6 months of enrollment
15) Use of strong CYP3A4 inducers within 1 week prior to the first dose of IP
16) Known hypersensitivity to MMB, gemcitabine and/or nab-paclitaxel, their metabolites, or formulation excipients
17) Uncontrolled hypertension (seated systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) at Screening
18) QTcF interval > 450 msec, unless attributed to bundle branch block
19) Pregnant |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Lead-in:
- Incidence of Dose Limiting Toxicity
- Pharmacokinetic parameters (Cmax, Ctau and AUCtau, if available) for MMB.
Randomized treatment:
- Overall survival, defined as the interval from randomization to death from any cause |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Each treatment cycle is 28 days. Subjects will undergo 3 weekly visits each cycle. Staging scan will be performed at baseline and approximately every 8 weeks thereafter. After discontinuation of treatment, subjects will be followed for safety for 30 days and for survival approximately every 3 months for up to 5 years.
|
|
| E.5.2 | Secondary end point(s) |
Lead-in:
- Overall survival – defined as the interval from first dose date of IP in lead-in phase to death from any cause.
- Progression-free survival – defined as the interval from first dose date of IP in lead-in phase to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST criteria v1.1. Data from survival, non-progressing subjects will be censored at the earliest of the time of initiation of anti-tumor therapy other than the study treatment or the last time that lack of definitive disease progression was objectively documented while on study.
- Overall response rate - defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1.
Randomized treatment: Progression-free survival (PFS) and overall response rate (ORR).
- Progression-free survival (PFS) – defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is progression based on RECIST v1.1 criteria. Data from survival, non-progressing subjects will be censored at the earliest of the time of initiation of anti-tumor therapy other than the study treatment or the last time that lack of definitive disease
progression was objectively documented while on study.
- Overall response rate (ORR) – defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each treatment cycle is 28 days. Subjects will undergo 3 weekly visits each cycle. Staging scan will be performed at baseline and approximately every 8 weeks thereafter. After discontinuation of treatment, subjects will be followed for safety for 30 days and for survival approximately every 3 months for up to 5 years.
|
|
| 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 | Yes |
| 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) | 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 | 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) | 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 109 |
| 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 |
| Australia |
| Canada |
| Czech Republic |
| France |
| Germany |
| Hong Kong |
| Hungary |
| Italy |
| Korea, Republic of |
| Poland |
| Spain |
| Taiwan |
| 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 | 7 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 7 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
