A Study of Durvalumab in Patients With BR PDA Following Neoadjuvant Therapy and Successful Surgical Resection

NCT03038477 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 16-0546.cc
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-arm, open-label, phase II study of in adult patients who have successfully undergone R0/R1 resection of PDAs following neoadjuvant chemotherapy and completion of adjuvant chemotherapy. Within 1-3 months of treatment completion, patients will be enrolled and randomized at a 1:1 ratio to receive durvalumab versus observation.

Conditions

Pancreatic Cancer

Keywords

Borderline Resectable Pancreatic Ductal Adenocarcinoma; Durvalumab

Outcome Measures

Primary Outcomes (1)

• The number of subjects with disease free survival (DFS)

  Disease free survival (DFS) is defined as the time from randomization to the first of either disease recurrence or death from any cause.

  26 Months

Secondary Outcomes (2)

• Overall survival (OS) of all patients

  26 months

• The number of patients who experience adverse events

  26 months

Study Arms (2)

Durvalumab

EXPERIMENTAL

Patients in Arm A will be given anti-PD-L1 antibody, durvalumab, every 2 weeks for a maximum of 26 doses if there is no radiographic evidence of disease recurrence. For Arm A, one cycle constitutes two durvalumab treatments on Day 1 and Day 15, respectively, repeated every 28 days.

Drug: Durvalumab

No Durvalumab

NO INTERVENTION

Patients in Arm B will be observed.

Interventions

Durvalumab DRUG

1500mg of Durvalumab will be given every 4 weeks (Q4W) for 12 months in patients enrolled in Arm A.

Also known as: MEDI4736, anti-PD-L1 antibody

Durvalumab

Eligibility Criteria

• Age: 18 Years - 101 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age \> 18 years at time of study entry, age \> 20 years for Japanese subjects.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \> 2 years
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Absolute lymphocyte count ≥ 500/mm3
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). \<\<This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.\>\>
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:
• Males:
• Creatinine CL (mL/min) = (Weight (kg) x (140 - Age)) / (72 x serum creatinine (mg/dL))
• Females:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study
• Participation in another clinical study with an investigational product during the last 4 weeks.
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab.
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 28 days prior to the first dose of study drug (≤ 28 days prior to the first dose of study drug for subjects who have received prior TKIs \[e.g., erlotinib, gefitinib and crizotinib\] and within 6 weeks for nitrosourea or mitomycin C). (If sufficient wash-out time has not occurred due to the schedule or PK properties of an agent, a longer wash-out period may be required.)
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Any unresolved toxicity (\>CTCAE grade 2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)
• History of primary immunodeficiency

Sponsors & Collaborators

• University of Colorado, Denver: lead
• AstraZeneca: collaborator

Study Sites (1)

University of Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Wells Messersmith, MD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2017
• First Posted: January 31, 2017
• Study Start: June 12, 2017
• Primary Completion: April 1, 2019
• Study Completion: April 1, 2019
• Last Updated: September 14, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)