E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Metastatic Pancreatic Cancer |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033605 |
E.1.2 | Term | Pancreatic cancer metastatic |
E.1.2 | System Organ Class | 100000016906 |
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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 |
To compare the efficacy of AM0010 in combination with FOLFOX versus FOLFOX alone in patients with metastatic pancreatic cancer as measured by OS. |
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E.2.2 | Secondary objectives of the trial |
To compare the efficacy of AM0010 in combination with FOLFOX versus FOLFOX alone as measured by:
• PFS
• ORR by RECIST v.1.1
To compare the safety and tolerability of AM0010 in combination with FOLFOX versus FOLFOX alone. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The presence of metastatic pancreatic adenocarcinoma plus 1 of the following:
a. Histological diagnosis of pancreatic adenocarcinoma confirmed pathologically,
OR
b. Pathologist confirmed histological/cytological diagnosis of adenocarcinoma consistent with pancreas origin in conjunction with either:
i. The presence of a mass in the pancreas, OR
ii. A history of resected pancreatic adenocarcinoma.
2. Measureable disease per RECIST v.1.1
3. Patient must have documented tumor progression during or following a gemcitabine containing regimen to treat metastatic disease.
4. Only one prior gemcitabine containing therapy and no other prior therapies for metastatic disease.
5. Diagnosis of tumor progression (by CT or MRI scan or clinical progression) on first -line therapy within 28 days prior to randomization.
6. Male or non-pregnant, non-lactating female, ≥ 18 years or age.
a. If a female patient is of child-bearing potential, as evidenced by regular menstrual periods, she must have a negative serum pregnancy test (β-hCG) documented prior to the first administration of study drug.
b. If sexually active, the patient must agree to use contraception considered adequate and appropriate by the Investigator during the period of administration of study drugs. In addition, male and female patients must utilize contraception after the end of the treatment as recommended in the individual drugs comprising FOLFOX product’s Summary of Product Characteristics or Prescribing Information provided in the study manual and the AM0010 Investigator’s Brochure.
7. Provide signed written informed consent.
8. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0
–1; two observers will be required to assess ECOG. If discrepant, the one with the worst assessment will be considered to be true.
9. Patient must have completed prior chemotherapy at least 2 weeks (washout period) prior to randomization and recovered from toxicity to Grade 1 or baseline.
10. Patients must not have received previous radiation therapy, surgery, or investigational therapy for the treatment of advanced metastatic disease. Patients having received cytotoxic doses of gemcitabine or any other chemotherapy in the adjuvant setting are not eligible for this study.
11. Willingness and ability to comply with study requirements.
12. Patient has adequate organ function by the following laboratory assessments at baseline (obtained ≤21 days prior to randomization):
Hematologic
* Platelets ≥100×109/L
* Hemoglobin ≥9.0 g/dL
* Absolute Neutrophil Count (ANC) ≥1.5×109/L
* Patient has acceptable coagulation values obtained ≤21 days prior to randomization as demonstrated by prothrombin time (PT) and partial thromboplastin time (PTT) ≤1.5 ULN (if on Coumadin, patient must be changed to LMW heparin (LMWH) or on Factor Xa anticoagulant with a half
-life of less than 24 hours.
Hepatic
* AST/ALT ≤ 3 × ULN (if liver metastases are present, ≤ 5 × ULN)
* Alkaline phosphatase ≤ 2.0 × ULN (if liver metastases are present, ≤ 5 × ULN)
* Total bilirubin ≤ 1.5 × ULN
* Albumin ≥ 3.0
Renal
* Serum creatinine < 2.0 or calculated creatinine clearance ≥ 60 mL/min for patients with serum creatinine levels above the institutional normal value. If using creatinine clearance, actual body weight should be used for calculating creatinine clearance (e.g., using Modification of Diet in Renal Disease (MDRD) formula, (Levey, Coresh et al. 2006). For patients with a body mass index (BMI) > 30 kg/m2, lean body weight should be used instead.
13. Patient must have a life expectancy of ≥ 4 months in the opinion of the
Investigator
14 No peripheral neuropathy (< Grade 2)
15. No known history of dihydropyrimidine dehydrogenase deficiency (DPD)
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E.4 | Principal exclusion criteria |
1. Diagnosis of pancreatic islet neoplasm, acinar cell carcinoma, non-adenocarcinoma (i.e., lymphoma, sarcoma), adenocarcinoma originating from the biliary tree, or cystadenocarcinoma.
2. Patient has experienced a decrease in ECOG PS between screening visit and within 72 hours prior to randomization.
3. Patient on Coumadin and not willing to change to LMW H or oral Factor II or Xa inhibitor with half -life of less than 24 hours.
4. Patient has received prior treatment with AM0010 or fluoropyrimidine/platinum containing regimen.
5. History of prior malignancy, except for adequately treated in situ cancer or basal cell or squamous cell skin cancer or other cancers (e.g., breast, prostate) for which the patient has been disease free for at least 3 years.
6. Any serious medical condition, laboratory abnormality, psychiatric illness, or comorbidity that, in the judgment of the investigator, would make the patient inappropriate for the study.
7. Serious systemic fungal, bacterial, viral, or other infection that is not controlled or requires intravenous antibiotics.
8. Patients who are intolerant to gemcitabine containing regimens are not eligible.
9. History of positivity (regardless of immune status) for human immunodeficiency virus (HIV).
10. Known history of chronic active or active viral hepatitis A, B, or C infection
11. Clinically significant bleeding within two weeks prior to randomization (e.g., gastrointestinal (GI) bleeding, intracranial hemorrhage).
12. Pregnant or lactating women.
13. Patients with a history of immune mediated neurological disorders such as multiple sclerosis, Guillain-Barré, or inflammatory CNS/PNS disorders.
14. Myocardial infarction within the last 6 months prior to randomization, symptomatic congestive heart failure (New York Heart Association Classification > Class II, (Appendix E), unstable angina, or unstable cardiac arrhythmia requiring medication.
15. Clinically significant ascites defined as requiring ≥ 1 paracentesis every 2 weeks.
16. Major surgery, defined as any surgical procedure that involves general anesthesia and a significant incision (i.e., larger than what is required for placement of central venous access, percutaneous feeding tube, or biopsy), within 28 days prior to randomization or anticipated surgery during the study period.
17. Prior history of receiving immune modulators including, but not limited to, anti-CTLA4, anti-PD1, anti-PD-L1 18.
18. Peripheral neuropathy (> Grade 1)
19. Known history of dihydropyrimidine dehydrogenase deficiency (DPD)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is OS is defined as the time from date of randomization to death due to any cause. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Throughout entire study duration |
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E.5.2 | Secondary end point(s) |
The secondary endpoints of the study include:
• PFS is defined as the time from date of randomization to the earlier of first documentation of definitive disease progression or death due to any cause
• ORR is defined as the proportion of patients who achieve a CR or PR as assessed by RECIST v.1.1 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout entire study duration |
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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 | No |
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) | 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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 65 |
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 |
Austria |
Belgium |
Canada |
France |
Germany |
Ireland |
Italy |
Korea, Republic of |
Poland |
Spain |
Taiwan |
United Kingdom |
United States |
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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
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After occurence of 393 deaths. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |