Phase Ib/II Study of MEDI4736 Evaluated in Different Combinations in Metastatic Pancreatic Ductal Carcinoma

NCT ID: NCT02583477

Last Updated: 2019-08-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-25
• Study Completion Date: 2018-07-09

Brief Summary

A Phase Ib and II Open-Label, Multi-Center Study of MEDI4736 Evaluated in Different Combinations (with chemotherapy or AZD5069) in Patients with Metastatic Pancreatic Ductal Adenocarcinoma

Detailed Description

This is a Phase Ib and II open-label, multi-center study to evaluate the safety, tolerability, pharmacodynamics, and antitumor activity of MEDI4736 in combination with chemotherapy or AZD5069 in patients with pancreatic ductal adenocarcinoma (PDAC). This study will consist of 2 independent cohorts.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MEDI4736 +nab-paclitaxel + gemcitabine

MEDI4736 in combination with nab-paclitaxel + gemcitabine chemotherapy regimen via IV infusion

Group Type: EXPERIMENTAL

MEDI4736 in combination with nab-paclitaxel and gemcitabine

Intervention Type: DRUG

MEDI4736 in combination with nab-paclitaxel + gemcitabine chemotherapy regimen via IV infusion

MEDI4736+AZD5069

MEDI4736 via IV infusion and oral AZD5069

Group Type: EXPERIMENTAL

MEDI4736 in combination with AZD5069

Intervention Type: DRUG

MEDI4736 via IV infusion and oral AZD5069

Interventions

MEDI4736 in combination with nab-paclitaxel and gemcitabine

MEDI4736 in combination with nab-paclitaxel + gemcitabine chemotherapy regimen via IV infusion

Intervention Type: DRUG

MEDI4736 in combination with AZD5069

MEDI4736 via IV infusion and oral AZD5069

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically or cytologically confirmed metastatic PDAC, no more than 1 prior chemotherapy regimen or treatment-naïve patients

2. Eastern Cooperative Oncology Group 0 or 1

3. 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

4. MEDI4736 + nab-paclitaxel + gemcitabine chemotherapy cohort: treatment-naïve patients with metastatic PDAC who have received no previous systemic chemotherapy 5 MEDI4736 + Cohort: Patient should receive no more than 1 prior systemic chemotherapy regimen.

6. Life expectancy ≥ 12 weeks. 7. ECOG PS of 0 or 1 8. Adequate organ and bone marrow function 9. Ability to undergo during screening a tumor biopsy that is adequate for biomarker analysis.

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. Major surgical procedure within 21 days prior to the first dose of IP.

4. Patients weighing less than 30 kg

5. History of leptomeningeal carcinomatosis

6. Ascites requiring intervention

7. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy

8. Current or prior use of immunosuppressive medication within 14 days of first dose

9. Brain metastases or spinal cord compression.

10. Medi4736+AZD5069 Cohort only: received any potent and moderate cytochrome CYP3A4 inhibitors, potent and moderate CYP3A4 inducers, P-gp substrates, BCRP substrates, sensitive CYP2B6 substrates, warfarin and coumarin derivatives, or herbal supplements within 14 days of the first dose of study treatment

11. Uncontrolled intercurrent illness

12. Other malignancy within 5 years except for noninvasive malignancies

13. Mean QT interval ≥470 ms

14. Active infection

15. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP

16. 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

17. Prior exposure to immune-mediated therapy

18. Known allergy or hypersensitivity to IP formulations or to other human monoclonal antibodies

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeff Evans, M.D

Role: PRINCIPAL_INVESTIGATOR

Beatson Institute, University of Glasgow, Garscrube Estate, Switchback Rd. Glasgow, UK, G61 1BD

Locations

Research Site

Rochester, New York, United States

Research Site

Cambridge, , United Kingdom

Research Site

Glasgow, , United Kingdom

Research Site

London, , United Kingdom

Research Site

London, , United Kingdom

Research Site

Manchester, , United Kingdom

Research Site

Metropolitan Borough of Wirral, , United Kingdom

Countries

United States; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3998&filename=d4198c00003-csp-v5-redact.pdf

CSP redacted

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3998&filename=d4198c00003-sap-ed-1-redact.pdf

SAP redacted

Other Identifiers

D4198C00003

Identifier Type: -

Identifier Source: org_study_id