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A Pilot Study to Test the Feasibility of the Combination of Gemcitabine and Anti-PD1 Monoclonal Antibody (CT-011) in the Treatment of Resected Pancreatic Cancer

Phase 2
18 Years
Not Enrolling
Pancreatic Neoplasms, Cancer of the Pancreas, Neoplasms Pancreatic, Pancreatic Cancer, Pancreas Cancer

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Trial Information

A Pilot Study to Test the Feasibility of the Combination of Gemcitabine and Anti-PD1 Monoclonal Antibody (CT-011) in the Treatment of Resected Pancreatic Cancer


- In 2009, 49,096 patients were diagnosed with pancreatic cancer. Pancreatic cancer
carries a poor prognosis with an overall 5-year relative survival rate of 5.6%.

- One of the leading causes for immune suppression in cancer patients was suggested to be
associated with the elevated expression of programmed cell death 1 ligand 1 (PD-L1)
human B7 homolog 1 (B7-H1) at tumor-involved sites, either by the tumor itself or by
surrounding cells like regulatory immune cells, resulting in the local suppression and
apoptosis of tumor infiltrating effector lymphocytes.

- CT-011 is a humanized immunoglobulin G 1 (IgG1) kappa recombinant monoclonal antibody
against PD-1 receptor that blocks the interaction of PD-L1 with PD-1. CT-011
specifically binds to an epitope that is shared between the murine and the human PD-1
receptors on activated T cells, B cells, natural killer (NK) cells, and myeloid cells
(CD14+ cells) and primarily functions in effector/memory T lymphocytes and in NK cells.
In a functional bioassay, CT-011 was demonstrated to block the activity of PD-1 and to
operate on CD4+CD45RO+ effector/memory T lymphocytes leading to attenuation of
apoptotic processes.

- CT-011 was studied in experimental murine tumor models of melanoma, lung cancer,
fibrosarcoma, leukemia/lymphoma and colorectal carcinoma and was shown to inhibit tumor
growth and extend the survival of tumor-bearing nude mice, and to generate
tumor-specific protection against tumor re-challenge.

- Recent findings have demonstrated that chemotherapies like paclitaxel, etoposide or
fluorouracil (5-FU) induce the expression of the PD-L1 on tumor cell lines leading to
an immune-suppressive environment and promoting PD-L1-mediated T cell apoptosis


- Primary endpoint: To determine the feasibility and safety of the combination of CT-011
and Gemcitabine in patients after primary macroscopic resection of pancreatic

- Secondary endpoint: To determine if the addition of CT-011 to Gemcitabine can improve
the median disease-free survival in resected pancreatic cancer.


- Adult patients with histologic verification of adenocarcinoma of the pancreas (T1-3,
N0-1) who have undergone surgical resection within the past 4-8 weeks.

- Must meet all laboratory safety criteria and not have active or history of autoimmune
disease or conditions, be treated with immunosuppressive drugs, or require the use of
systemic steroids.

- Pregnant or nursing women will be excluded. Subjects with active infection, human
immunodeficiency virus (HIV), Hepatitis B or C will be excluded.


- Eligible subjects will receive adjuvant combination CT-011 and Gemcitabine.

- Gemcitabine will be given at a dose of 1000mg/m^2 by intravenous infusion over 30
minutes on Days 8, 15 and 22 of each cycle.

- CT-011 will be given at a dose of 3mg/kg by intravenous infusion over 2 hours on day 1,
one week prior to the first Gemcitabine infusion of each cycle.

- Treatment will be continued for a total of 6 cycles or until disease recurrence or
grade IV non-hematological toxicity if occurred before the completion of 6 cycles.

- The study will be conducted as an optimal two-stage phase II trial, in order to rule
out an unacceptably low 50% of patients who do not receive the full dose of CT-011
(p0=0.50) in favor of a modestly high 80% fraction who receive the full dose of CT-011
(p1=0.80). It is anticipated that up to 32 patients may be enrolled onto this trial.

Inclusion Criteria


- Histologic diagnosis of adenocarcinoma of the pancreas after primary macroscopic
resection staged as T1-3, N0-1 by AJCC staging criteria.

- Patients must be 4- 8 weeks removed from primary resection and adequately recovered
from surgery.

- Patients cannot have had any previous systemic therapy including radiation or
chemotherapy, except for the primary resection. Primary intraoperative chemotherapy
will be allowed.

- Patients who have no contraindications for Gemcitabine treatment.

- Patients must be 18 years or older.

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1.

- Patients must have adequate:

- Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to

- Platelets greater than or equal to 100,000/mm^3.

- Renal function: Creatinine less than or equal to 1.5 times the institutional upper
limit normal (ULN).

- Hepatic function: Bilirubin less than or equal to 1.5 times the ULN except patients
with Gilbert's disease. Serum glutamic oxaloacetic transaminase (SGOT) and alkaline
phosphatase less than or equal to 2.5 times the ULN.

- Normal Cardiac function: Electrocardiogram (ECG) with no evidence of arrhythmia,
conduction abnormality or ischemia. No active coronary artery disease; No New York
Heart Association class II, III or IV disease; no arrhythmia requiring treatment.

- Patients must be willing to travel to Georgia Health Sciences University Cancer
Center for treatment and follow up visits (for blood draw, physical exam, and imaging
every two months and up to two years during the follow up period).

- Willing to use effective birth control measures: Since the effects of CT-011 on the
developing human fetus are unknown and potentially harmful, women of child-bearing
potential and men with partners of childbearing potential must agree to use adequate
contraception (hormonal or double barrier method of birth control or complete
abstinence) prior to study entry and for the duration of study participation and for
one month after the last dose of investigational agent. Should a woman become
pregnant or suspect she is pregnant while participating in this study, she should
inform her treating physician immediately.

- Patients must understand and sign an informed consent document that explains the
neoplastic nature of his/ her disease, the procedures to be followed, the
experimental nature of the treatment, alternative treatment and potential risks and


- Patients with R1 resections.

- Concurrent treatment with any other cancer therapies including radiation,
chemotherapy or other investigational agent(s).

- History of a second active malignancy in the last 2 years other than non-melanoma
skin cancers or carcinoma in situ of the cervix.

- Patients who have active or history of autoimmune disease/symptom/conditions
including: type I diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE),
ulcerative colitis, Crohn's Disease, multiple sclerosis (MS), ankylosing spondylitis.
Chronic diabetes mellitus, vitiligo or stable hypothyroidism are not considered
exclusion criteria.

- Patients being chronically treated with immunosuppressive drugs such as cyclosporin,
adrenocorticotropic hormone (ACTH).

- Concurrent use of systemic steroids except physiologic doses for systemic steroid
replacement or local therapy. Physiologic doses are defined as daily systemic therapy
used to replace endogenous steroids because of hypothalamic pituitary adrenal (HPA)
axis dysfunction or other physiological abnormality.

- Patients who have acquired, hereditary, or congenital immunodeficiencies including
cellular immunodeficiencies, hypogammaglobulinemia and dysgammaglobulinemia.

- Serious active infection at the time of pre-study screening.

- Positive human immunodeficiency virus (HIV) or Hepatitis C antibodies or Hepatitis B
anti-core antibodies.

- Pregnant women or nursing mothers are ineligible.

- Patients with a history of chronic radiation injury/inflammation due to the risk of
perforation in the event of autoimmune inflammation, or a history of chronic diarrhea
due to previous treatments or surgery.

- If, in the opinion of the Principal or Associate Investigators, it is not in the best
medical interest of the patient to enter this study, the patient will not be eligible

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the feasibility and safety of the combination of CT-011 and Gemcitabine in patients after primary macroscopic resection of pancreatic adenocarcinoma.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Samir N. Khleif, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Georgia Regents University


United States: Food and Drug Administration

Study ID:




Start Date:

September 2012

Completion Date:

February 2017

Related Keywords:

  • Pancreatic Neoplasms
  • Cancer of the Pancreas
  • Neoplasms Pancreatic
  • Pancreatic Cancer
  • Pancreas Cancer
  • Adjuvant Therapy
  • Recombinant Monoclonal Antibody
  • Adenocarcinoma of the Pancreas
  • Vaccination
  • PD-1 Receptor
  • Pancreas Cancer
  • Pancreatic Cancer
  • Neoplasms
  • Pancreatic Neoplasms



Georgia Health Sciences UniversityAugusta, Georgia  30912