Study of MEDI4736, when used in combination with chemotherapy agents or AZD5069, as first or second line in metastatic Pancreatic Ductal Adenocarcinoma

Phase 1

Active, not recruiting

• Conditions: Adult patients (aged =18 years) with histologically or cytologically confirmed metastatic pancreatic ductal adenocarcinoma who are treatment naive or have tumor progression following prior standard first-line 5-FU-containing or gemcitabine-containing chemotherapy.; MedDRA version: 20.0 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003639-37-GB
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-01-30
• Study Completion: 2018-07-09
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Not specified
• Target Recruitment: 27

Inclusion Criteria

1. Age =18 years at the time of screening.
2. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
3. Histologically or cytologically confirmed metastatic PDAC, no more than 1 prior systemic chemotherapy regimen or treatment-naïve patients
4. Life expectancy = 12 weeks.
5. Eastern Cooperative Oncology Group 0 or 1
6. At least 1 lesion, not previously irradiated, that can be accurately measured at
baseline as =10 mm in the longest diameter (except lymph nodes, which must have short axis =15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) scan and that is suitable for accurate repeated measurements
-Patient should receive no more than 1 prior chemotherapy regimen or any other systemic therapy for recurrent/metastatic PDAC.
7. Adequate organ and bone marrow function as defined below:
? Hemoglobin =9 g/dL
? Albumin =3 g/dL
? Absolute neutrophil count =1500/mm3
? Platelet count =100000/mm3
? Serum bilirubin =1.5 × the upper limit of normal (ULN). ?
ALT and AST =2.5 × ULN; for patients with hepatic metastases, ALT and AST =5 × ULN
Serum creatinine =1.5 mg/dL or calculated creatinine clearance =40 mL/min
8. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female premenopausal patients
9. Mandatory tumor biopsy at screening
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 12

Exclusion Criteria

1. Any concurrent chemotherapy, investigational product , biologic, or hormonal therapy for cancer treatment.
2. Receipt of any investigational anticancer therapy within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of study treatment.
3. Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study.
4. Receipt of last dose of an approved anticancer therapy within 21 days prior to the first dose of study treatment.
5. Major surgical procedure (as defined by the Investigator) within 21 days prior to the first dose of IP
6. Patients weighing less than 30 kg.
7. History of leptomeningeal carcinomatosis
8. Ascites requiring intervention
9. Brain metastases or spinal cord compression
10. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
11. Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736. with exceptions that Intranasal, inhaled, or topical steroids; or local steroid injections; Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent; Steroids as premedication for hypersensitivity reactions and chemotherapy induced nausea and vomiting.
12.Current or prior use of immunosuppressive medication within 14 days before the first dose of MEDI4736
13. History of organ transplant that requires use of immunosuppressive agents.
14. Active autoimmune disorders , or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment
- Prior exposure to immune-mediated therapy
- Has received any potent and moderate cytochrome P450 (CYP)3A4 inhibitors, potent and moderate CYP3A4 inducers, P-glycoprotein substrates (digoxin and dabigatran), breast cancer resistance protein substrates (topotecan), sensitive CYP2B6 substrates (bupropion and efavirenz), warfarin and coumarin derivatives, or herbal supplements within 14 days of the first dose of study treatment
15. Uncontrolled intercurrent illness
16. Other malignancy within 5 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin, prostate cancer or ductal carcinoma in situ of the breast that has/have been surgically cured
17. Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) =470 ms calculated from 3 ECG reports
18. History of active primary immunodeficiency.
19. Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus.
20. Active infection including hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
21. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
22. Female patients who are pregnant or breastfeeding, or male or female patients of reproductive potential who are not employing an effective method of birth control (see Section 3.8).
23. Known allergy or hy

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified