Purpose

This is an open-label, three-cohort, phase Ib study to determine the safety, recommended phase 2 dose (RP2D), and efficacy of Stereotactic Body Radiation Therapy (SBRT) in combination with either (A) MEDI4736 alone, (B) tremelimumab alone, or (C) the combination of MEDI4736 and tremelimumab for patients with unresectable locally advanced adenocarcinoma of pancreas.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Criteria


Inclusion:

- Histopathological confirmation of pancreatic adenocarcinoma prior to study entry.

- Unresectable and non-metastatic disease

- At least 1 measurable metastatic lesion by RECIST 1.1, defined as at least one lesion
that can be accurately measured in at least one dimension (longest diameter to be
recorded) as >20 mm with conventional techniques, or as >10 mm with spiral computed
tomography (CT) scan, and that is accessible for biopsy.

- Age >18 years

- ECOG performance status 0-1

- Normal organ and marrow function as defined below:

Absolute Neutrophil Count > 1,000/mcL Platelets ≥ 75,000/mcL Total Bilirubin ≤ 2 x ULN
Serum Albumin ≥ 2.5 g/dl ALT or AST up to 3 x ULN if no liver metastases or ALT or AST up
to 5 x ULN if liver metastases present Creatinine < 2 x institution upper limit of normal
OR Creatinine Clearance > 45 mL/min/1.73 m2, as calculated below, for patients with
creatinine levels above institutional normal

- No history of another malignancy in the past 5 years, except for treated non-melanoma
skin cancer, superficial bladder cancer, or carcinoma-in-situ of the cervix

- No coexisting medical problems that would limit compliance with the study

- Ability to understand and sign a written informed consent document. Patient must have
willingness and ability to comply with scheduled visits, treatment plans, laboratory
tests and other study procedures.

- Female subjects of childbearing potential must have a negative serum pregnancy test
prior to study entry

- Female subjects of childbearing potential and males must agree to use a highly
effective method of contraception for the duration of study treatment, and for six
months after discontinuation of the study drug.

Exclusion:

- Resectable, borderline resectable or metastatic disease

- Prior chemotherapy, targeted therapy, immunotherapy, clinical trials or radiotherapy
for pancreatic cancer.

- Active or history of concomitant therapy with any of the following: interleukin (IL)
2, interferon, or other non-study immunotherapy regimens, immunosuppressive agents,
other investigational therapies, or chronic use of systemic corticosteroids (inhaled
and topical steroids are permitted)

- Active or history of chronic autoimmune disease with symptomatic disease within the 3
years before randomization.

- Active or history of inflammatory bowel disease (colitis, Crohn's disease), irritable
bowel disease, celiac disease, or other serious, chronic, gastrointestinal conditions
associated with diarrhea.

- Diverticulitis within the past 2 years.

- Active HIV infection

- Uncontrolled systemic disease including, but not limited to, ongoing or active
systemic infection, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.

- Brain metastases

- Patients should not be vaccinated with live attenuated vaccines within 1 month of
starting tremelimumab and MEDI4736 treatment.

- History of hypersensitivity reaction to human or mouse antibody products

- Evidence of pre-existing idiopathic pulmonary fibrosis on CT scan at baseline

- Unhealed surgical wound at time of treatment, or history of unhealed surgical wound
for more than 30 days

- History of an invasive secondary primary malignancy diagnosed within the previous 3
years, except for appropriately treated stage I endometrial or cervical carcinoma,
prostate carcinoma treated surgically or non-melanoma skin cancer.

- Non-protocol antineoplastic agents will not be permitted during this study

- Patients may not recieve other investigational agents.

- Pregnant or lactating women

- Subjects with dementia or significantly altered mental status that would prohibit
understanding or rendering of information and consent and compliance with the
requirements of the protocol.

- Subjects unable or unwilling to abide by the study protocol or cooperate fully.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort A: MEDI4736 + SBRT
MEDI4736 10 mg/kg IV every 2 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
  • Drug: MEDI4736
    anti-PD-L1 human monoclonal antibody
    Other names:
    • Durvalumab
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)
    Stereotactic body radiation therapy (SBRT) will be administered at the standard dose of 6 Gy daily for 5 days.
Experimental
Cohort B:Tremelimumab + SBRT
Tremelimumab 10 mg/kg IV every 4 weeks plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 10 Subjects
  • Drug: Tremelimumab
    anti-CTLA4 human monoclonal antibody
    Other names:
    • CP-675,206
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)
    Stereotactic body radiation therapy (SBRT) will be administered at the standard dose of 6 Gy daily for 5 days.
Experimental
Cohort C: MEDI4736 + Tremelimumab + SBRT
MEDI4736 + Tremelimumab (recommended phase 2 IV dose for combination) plus Stereotactic Body Radiation (SBRT) 6 Gy x 5 Days, 16 Subjects
  • Drug: MEDI4736
    anti-PD-L1 human monoclonal antibody
    Other names:
    • Durvalumab
  • Drug: Tremelimumab
    anti-CTLA4 human monoclonal antibody
    Other names:
    • CP-675,206
  • Radiation: Stereotactic Body Radiation Therapy (SBRT)
    Stereotactic body radiation therapy (SBRT) will be administered at the standard dose of 6 Gy daily for 5 days.

Recruiting Locations

Montefiore Medical Center
Bronx, New York 10461
Contact:
Jennifer Chuy, MD
JCHUY@montefiore.org

More Details

NCT ID
NCT02868632
Status
Recruiting
Sponsor
New York University School of Medicine

Study Contact

Jennifer Wu, MD
212-263-6485
Jennifer.Wu@nyumc.org

Detailed Description

Patients with unresectable, locally advanced adenocarcinoma of pancreas will receive Stereotactic Body Radiation Therapy (SBRT) at a dose of 6 Gy daily, for 5 days. In Cohort A, where MEDI4736 is given, subjects will receive 10 mg/kg of MEDI4736 every 2 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours). In Cohort B, where tremelimumab is given, subjects will receive 10 mg/kg of tremelimumab every 4 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours). In Cohort C, where MEDI4736 and tremelimumab are given in combination, subjects will receive 10 mg/kg of tremelimumab every 4 weeks, on the same day as, but after the first dose of SBRT is delivered (within 4 hours), followed by 10 mg/kg of MEDI4736 every 4 weeks.

Correlative Studies The investigators will evaluate immune changes in peripheral blood samples and in tumor biopsy fine needle aspirate (FNA) specimens pre- and post- treatment from the 3 cohorts that involve the combination of stereotactic body radiation therapy (SBRT) with either (A) MEDI4736 alone, (B) tremelimumab alone, or (C) the combination of MEDI4736 and tremelimumab. FNA biopsies will be done at baseline (within 30 days of treatment initiation) and Day 28 of cycle 2 (between days 22-28 of cycle 2).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.