Trial record 1 of 1 for:    11-C-0100
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Gemcitabine and CT-011 for Resected Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Georgia Regents University
Sponsor:
Information provided by (Responsible Party):
Samir N. Khleif, Georgia Regents University
ClinicalTrials.gov Identifier:
NCT01313416
First received: March 10, 2011
Last updated: October 15, 2013
Last verified: October 2013

March 10, 2011
October 15, 2013
September 2012
February 2014   (final data collection date for primary 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. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
To determine the feasibility and safety of the combination of CT-011 and Gemcitabine in patients after primary macroscopic resection of pancreatic adenocarcinoma.
Complete list of historical versions of study NCT01313416 on ClinicalTrials.gov Archive Site
To determine if the addition of CT-011 to Gemcitabine can improve the median disease-free survival (DFS) in resected pancreatic cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
To determine if the addition of CT-011 to Gemcitabine can improve the median disease-free survival (DFS) in resected pancreatic cancer.
Not Provided
Not Provided
 
Gemcitabine and CT-011 for Resected Pancreatic Cancer
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

Background:

  • Many doctors believe that individuals who have had surgery to remove pancreatic cancer should receive additional treatment, known as adjuvant therapy or adjuvant treatment, to prevent the cancer from returning. One chemotherapy drug that has been found to be effective in some patients with pancreatic cancer is called gemcitabine; it has been shown to improve patient survival by 6 months. Researchers are searching for new drugs or drug combinations to improve on these results.
  • Some chemotherapy drugs kill cancer cells directly, but appear to prevent the immune system from helping in that fight. The experimental drug CT-011 is designed to help the immune system remain active to fight cancer cells. CT 011 has been tested in laboratories and studied for use with a number of other cancers, but it has not been given in combination with gemcitabine as a treatment for pancreatic cancer.

Objectives:

- To test the safety and effectiveness of chemotherapy drugs gemcitabine and CT-011 as a follow-up treatment for pancreatic cancer that has been surgically removed.

Eligibility:

- Individuals at least 18 years of age who have had surgery to remove pancreatic cancer and have not had other types of follow-up treatments.

Design:

  • Participants will be screened with a full medical history and physical examination, blood and urine tests, and imaging studies.
  • Participants will receive gemcitabine and CT-011 in 28-day cycles of treatment.
  • Participants will receive CT-011 on the first day of every 28-day cycle. One week later (Day 8), participants will receive gemcitabine, and will have two additional doses of gemcitabine in the following 2 weeks (days 15 and 21).
  • Participants will be monitored with frequent blood and urine tests throughout their treatment visits. Every other cycle (about every 2 months), participants will also have imaging studies to evaluate the experimental treatment.
  • Participants who do not have serious side effects and remain cancer-free may receive this drug combination every 28 days for a total of 6 cycles.
  • Participants will have follow-up visits with additional blood tests (including apheresis to collect red blood cells) every 2 months after stopping treatment for up to 2 years.

Background:

  • 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

Objectives:

  • Primary endpoint: To determine the feasibility and safety of the combination of CT-011 and Gemcitabine in patients after primary macroscopic resection of pancreatic adenocarcinoma.
  • Secondary endpoint: To determine if the addition of CT-011 to Gemcitabine can improve the median disease-free survival in resected pancreatic cancer.

Eligibility:

  • 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.

Design:

  • 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.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Pancreatic Neoplasms
  • Cancer of the Pancreas
  • Neoplasms Pancreatic
  • Pancreatic Cancer
  • Pancreas Cancer
  • Biological: CT-011
    3mg/kg, intravenous (IV) day 1 of each cycle over 2 hours. (Must be administered at the National Institutes of Health (NIH))
  • Drug: Gemcitabine
    1000mg/m^2 intravenous (IV) over 30 minutes on days 8, 15, and 22 of each cycle (This infusion may be administered at local oncologist office or the National Institutes of Health (NIH))
Experimental: Single arm
Combination CT-011 and Gemcitabine
Interventions:
  • Biological: CT-011
  • Drug: Gemcitabine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
29
February 2017
February 2014   (final data collection date for primary outcome measure)
  • 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 1,500/mm^3m.
  • 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 toxicities.

EXCLUSION CRITERIA:

  • 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
Both
18 Years and older
No
Contact: Pam Bourbo, RN 706-721-2730 pbourbo@georgiahealth.edu
United States
 
NCT01313416
11-C-0100
Yes
Samir N. Khleif, Georgia Regents University
Georgia Regents University
Not Provided
Principal Investigator: Samir N. Khleif, MD Georgia Regents University
Georgia Regents University
October 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP