Neoadjuvant CCRT With Gemcitabine/Durvalumab (MEDI4736) Followed by Adjuvant Gemcitabine/Durvalumab(MEDI4736) in Resectable or Borderline Resectable Pancreatic Cancer

NCT03572400 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: ESR-16-12315
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

\<Research Hypothesis\> The dynamics of immune cells by CCRT/Durvalumab will be uncovered. The combination of Durvalumab with concurrent chemoradiotherapy (CCRT/gemcitabine)) as neoaduvant treatment in resectable or borderline resectable pancreatic cancer is feasible and efficacious. The combination of Durvalumab with cytotoxic chemotherapy (gemcitabine) as an adjuvant treatment is feasible and efficacious. \<Objectives\> To assess the effect of Neoadjuvant CCRT with Gemcitabine/Durvalumab followed by adjuvant Gemcitabine/Durvalumab in resectable or borderline resectable pancreatic cancer Primary endpoint: 2 year-DFSR (disease-free survival rate) Secondary endpoints

• Efficacy: 2 year-OSR (overall survival rate), disease-free survival, overall survival, overall response rate (RECIST 1.1, ir response) after neoadjuvant CCRT, disease control rateEORTC QLQ-C30, the number of immune cells (TIL, macrophage, etc) in resected pancreatic tissue
• Safety: toxicity (CTCAE V), irAE, Exploratory Objective(s):
• To evaluate baseline measures and changes of immune systems and regulations by neoadjuvant CCRT with gemcitabine/Durvalumab in peripheral blood and tumor tissues
• To collect and store DNA from blood (according to ethical procedures) for future exploratory research into genes/genetic variation that may influence response (ie, distribution, safety, tolerability and efficacy) to study treatments and or susceptibility to disease (optional).

Conditions

Pancreatic Cancer

Keywords

pancreatic cancer; pancreas cancer

Outcome Measures

Primary Outcomes (1)

• Disease-free survival rate

  The percentage of time from enroll until disease progression or death

  8 weeks

Secondary Outcomes (5)

• Overall survival

  12weeks

• Disease-free survival

  8 weeks

• Overall response rate

  8 weeks

• Safety and tolerability as measured by number and grade of toxicity events

  2 weeks

• Disease control rate

  8 weeks

Study Arms (1)

Gemcitbine/Durvalumab

EXPERIMENTAL

Neoadjuvant CCRT with Gemcitbine/Durvalumab +Adjuvant Gemcitabine/Durvalumab Total 6 cycles, after that, Durvalumab q4wks up to total 1 year

Drug: Gemcitabine; Drug: Durvalumab

Interventions

Gemcitabine DRUG

Neoadjuvant: Weekly Gemcitabine 200 mg/m2 iv Adjuvant: Gemcitabine 1000mg/m2, D1, 8, 15 Q 4 weeks total 6cycles

Gemcitbine/Durvalumab

Durvalumab DRUG

Neoadjuvant: Durvalumab 1.5g iv Q 4weeks Adjuvant: Durvalumab 1.5g iv Q 4weeks for 1 year

Gemcitbine/Durvalumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally-required authorization (eg, 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\>=19 years at time of study entry
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of \>= 3months
• Histologically proven pancreatic ductal adenocarcinoma
• Resectable or borderline resectable based on AJCC Cancer staging system (8th ed)
• Chemotherapy -naïve for their pancreatic cancer
• Body weight \>30kg (for durvalumab monotherapy or durvalumab + novel)
• Adequate normal organ and marrow function as defined below: (NOTE TO AUTHOR: These are minimum criteria for studies in subjects with solid tumors and may need to be altered based on individual study requirements; please adjust as necessary) -Haemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) 1.5 (or 1.0) x (\> 1500 per mm3)
• Platelet count ≥ 100 (or 75) x 109/L (\>75,000 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:
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal subjects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

You may not qualify if:

• \- Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection)
• Systemic corticosteroids at physiologic doses not to exceed \<\<10 mg/day\>\> of prednisone or its equivalent
• Subjects with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Subjects with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician.
• \. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (eg, hormone replacement therapy) is acceptable. \<\<amend as required based on any combination studies with other anti-cancer agents\>\> 33. \<\<if applicable to the study\>\>Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 34. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• \. History of allogenic organ transplantation. 36. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Subjects without active disease in the last 5 years may be included but only after consultation with the study physician
• Subjects with celiac disease controlled by diet alone 37. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 38. 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 IP 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 39. History of leptomeningeal carcinomatosis 40. Brain metastases or spinal cord compression. 41. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart) \<\<for durvalumab monotherapy and durvalumab + tremelimumab combination studies this criterion can be removed. For durvalumab ± tremelimumab in combination with an agent with pro-arrhythmic potential or where effect of the combination on QT is not known if this criterion should be retained. Patient safety and the cardiac SKG should be consulted as needed\>\>.
• \. History of active primary immunodeficiency 43. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Sponsors & Collaborators

• Do-Youn Oh: lead
• AstraZeneca: collaborator

Study Sites (1)

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Gemcitabine; durvalumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Do-Youn Oh, MD, PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: June 28, 2018
• Study Start: November 29, 2018
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)