Ipilimumab and Gemcitabine Hydrochloride in Treating Patients With Stage III-IV or Recurrent Pancreatic Cancer That Cannot Be Removed by Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Northwestern University
Sponsor:
Collaborator:
Robert H. Lurie Cancer Center
Information provided by (Responsible Party):
Mary Mulcahy, Northwestern University
ClinicalTrials.gov Identifier:
NCT01473940
First received: October 19, 2011
Last updated: February 10, 2014
Last verified: February 2014
  Purpose

This phase I trial studies the side effects and best dose of ipilimumab when given together with gemcitabine hydrochloride in treating patients with stage III-IV or recurrent pancreatic cancer that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or tumor-killing substances to them. Drugs used in chemotherapy, such as gemcitabine hydrochloride, work in different ways to kill tumor cells or stop them from growing. Giving monoclonal antibody therapy together with chemotherapy may kill more tumor cells.


Condition Intervention Phase
Duct Cell Adenocarcinoma of the Pancreas
Recurrent Pancreatic Cancer
Stage III Pancreatic Cancer
Stage IV Pancreatic Cancer
Biological: ipilimumab
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ipilimumab and Gemcitabine for Advanced Pancreas Cancer: A Phase Ib Study

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • MTD of ipilimumab when given with gemcitabine hydrochloride in the treatment of pancreas adenocarcinoma [ Time Frame: After the 12 weeks of induction therapy ] [ Designated as safety issue: Yes ]
    Dose limiting toxicity (DLT) will be monitored by calculating the Bayesian predictive probability of a DLT given the data to date. All toxicities will be summarized in a descriptive manner as to type, frequency, attribution and timing by dose level. Safety will be evaluated for all treated patients using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.


Secondary Outcome Measures:
  • Response rate by mWHO and irRC [ Time Frame: At week 12 ] [ Designated as safety issue: No ]
  • Median time to progression as calculated by mWHO and irRC in patients who progress [ Time Frame: Monthly for 6 months and then every 3 months ] [ Designated as safety issue: No ]
  • Progression free survival (PFS) [ Time Frame: Monthly for 6 months and then every 3 months ] [ Designated as safety issue: No ]
  • Overall survival (OS) [ Time Frame: Monthly for 6 months and then every 3 months ] [ Designated as safety issue: No ]
  • Recovery of tumor immune surveillance: T-cell response to defined pancreatic cancer tumor antigens [ Time Frame: Prior to ipilimumab infusion at weeks 1, 4, 7, and 10, and then every 12 weeks starting at week 22 ] [ Designated as safety issue: No ]

Estimated Enrollment: 28
Study Start Date: April 2012
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (monoclonal antibody, chemotherapy)

INDUCTION: Patients receive ipilimumab IV over 90 minutes in weeks 1, 4, 7, and 10 and gemcitabine hydrochloride IV over 30 minutes in weeks 1-7 and 9-11.

MAINTENANCE: Beginning in week 22, patients receive ipilimumab IV over 90 minutes once every 12 weeks and gemcitabine hydrochloride IV over 30 minutes once weekly for 3 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment modifications may apply according to response.

Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Drug: gemcitabine hydrochloride
Given IV
Other Names:
  • dFdC
  • difluorodeoxycytidine hydrochloride
  • gemcitabine
  • Gemzar
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

OUTLINE: This is a dose-escalation study of ipilimumab.

INDUCTION: Patients receive ipilimumab intravenously (IV) over 90 minutes in weeks 1, 4, 7, and 10, and gemcitabine hydrochloride IV over 30 minutes in weeks 1-7 and 9-11.

MAINTENANCE: Beginning in week 22, patients receive ipilimumab IV over 90 minutes once every 12 weeks and gemcitabine hydrochloride IV over 30 minutes once weekly for 3 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Treatment modifications may apply according to response.

After completion of study treatment, patients are followed up monthly for 6 months and then every 3 months.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Willing and able to give written informed consent
  • Histologic or cytologic diagnosis of pancreas adenocarcinoma advanced or recurrent (stage III or IV) that is unresectable; histologic or cytologic pathology from any prior surgery is sufficient for diagnosis
  • Must have measurable disease by modified WHO criteria
  • White blood cells (WBC) >= 2000/uL
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelets >= 100 x 10^3/uL
  • Hemoglobin >= 9 g/dL (>= 80 g/L; may be transfused)
  • Creatinine =< 2.0 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Bilirubin =< 2.0 x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
  • No active or chronic infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
  • Performance status: Eastern Cooperative Oncology Group (ECOG) 0-1
  • Prior systemic therapy for advanced pancreas cancer with gemcitabine is prohibited; prior gemcitabine with radiotherapy for localized pancreas cancer is allowed provided disease is present outside of the radiated field; prior gemcitabine as adjuvant therapy to surgical resection is allowed provided 3 months or greater has elapsed between the last dose of gemcitabine and the detection of recurrent disease
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 26 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized; WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not post-menopausal; post-menopause is defined as: amenorrhea >= 12 consecutive months without another cause, or for women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level >= 35 mIU/mL; women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential
  • WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotrophin [HCG]) within 72 hours before the start of ipilimumab
  • Men of fathering potential must be using an adequate method of contraception to avoid conception throughout the study (and for up to 26 weeks after the last dose of investigational product) in such a manner that the risk of pregnancy is minimized
  • Patients on stable anticoagulation are eligible for enrollment; for patients on warfarin, prothrombin time (PT)/international normalized ratio (INR) should be monitored every 2 weeks during induction therapy, monthly thereafter, or more frequent as clinically indicated

Exclusion Criteria:

  • Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix
  • Autoimmune disease: Patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's Disease, are excluded from this study, as are patients with a history of symptomatic disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [eg, Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis)
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of adverse events (AEs), such as a condition associated with frequent diarrhea
  • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab)
  • A history of prior treatment with ipilimumab or prior tumor necrosis factor receptor superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor or agonist
  • Concomitant therapy with any of the following: interleukin (IL)2, interferon, or other non-study immunotherapy regimens; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids
  • WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 8 weeks after cessation of study drug, or have a positive pregnancy test at baseline, or are pregnant or breastfeeding
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (eg, infectious) illness
  • Patients with symptoms of partial or complete bowel obstruction and recent (within 6 month) history of fistula, intra-abdominal abscess or bowel perforation
  • Patients with a history or evidence of central nervous system (CNS) disease, including brain tumor, seizures not controlled with standard medical therapy or any brain metastases
  • Patients currently receiving radiation therapy or those having received radiation within 4 weeks of study entry
  • Patients with any known active infection or known history of tuberculosis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01473940

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Contact: Mary F. Mulcahy    312-695-4440    m-mulcahy@northwestern.edu   
Principal Investigator: Mary F. Mulcahy         
Sub-Investigator: Khashayarsha Khazaie, Ph.D. D.Sc.         
Sub-Investigator: Sheetal Kircher, MD         
Sponsors and Collaborators
Northwestern University
Robert H. Lurie Cancer Center
Investigators
Principal Investigator: Mary Mulcahy Northwestern University
  More Information

No publications provided

Responsible Party: Mary Mulcahy, Mary Mulcahy, MD, Northwestern University
ClinicalTrials.gov Identifier: NCT01473940     History of Changes
Other Study ID Numbers: NU 10I02, NCI-2011-03135, STU00045323
Study First Received: October 19, 2011
Last Updated: February 10, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antibodies
Antibodies, Monoclonal
Gemcitabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 28, 2014