AzTrials
AzTrials

Duct Cell Adenocarcinoma of the PancreasPhase 1NCT01473940

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

A Phase 1 study testing ipilimumab, gemcitabine hydrochloride and laboratory biomarker analysis in people with Duct Cell Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by Northwestern University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ipilimumab, gemcitabine hydrochloride and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
11 Jun 2012to 6 May 2018
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 17Show fewer
  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: Ipilimumab and Gemcitabine for Advanced Pancreas Cancer: A Phase Ib Study

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.

Read the 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.

Being tested
ipilimumab, gemcitabine hydrochloride, laboratory biomarker analysis
Medical subject headings
Pancreatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ipilimumabBiological

    Also called anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

    Given IV

  • gemcitabine hydrochlorideDrug

    Also called dFdC, difluorodeoxycytidine hydrochloride, gemcitabine, Gemzar

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01473940
Study groupRoleWhat they receive
Treatment (monoclonal antibody, chemotherapy)ExperimentalINDUCTION: 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.
Receives: Biological: ipilimumab; Drug: gemcitabine hydrochloride; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Dose Limiting Toxicities (DLTs) Seen in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination in Order to Define the Maximum Tolerated Dose (MTD)

    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 where grading is as follows:

    Mild (grade 1) Moderate (grade 2) Severe (grade 3) Life-threatening (grade 4) Fatal (grade 5)

    In general a DLT will be defined as any any of the following drug-related toxicities:

    Febrile neutropenia with grade 3/4 neutropenia Asymptomatic grade 4 neutropenia more than 7 days Grade 3 thrombocytopenia with grade 3-4 hemorrhage or grade 4 thrombocytopenia Non-hematologic toxicity grade 3 or 4 (with some protocol specified exceptions)

    DLTs will be used to determine the MTD for the expansion cohort of the study.

    *AST = Aspartate transamina

    Measured: During the 12 weeks of Induction Therapy

Secondary outcomes (5)

  1. Response Rate Using Immune-related Response Criteria (irRC) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination

    Response will be assessed using CT of MRI scans immune-related response criteria (irRC). The sum of all the products of diameters (SPD) at tumor assessment using the irRC for progressive disease incorporates the contribution of new measurable lesions. Each net percentage change in tumor burden per assessment using irRC accounts for the size and growth kinetics of both old and new lesions as they appear.

    irComplete Response (irCR)-Complete disappearance of all index lesions. irPartial Response (irPR)-Decrease of 50% or greater in the sum of products of the two largest perpendicular diameters of all index and all new measurable lesions (i.e., percentage change in tumor burden) irStable Disease (irSD)-does not meet criteria for irCR or ir PR, in the absence of progressive disease.

    irProgressive Disease (irPD)-At least 25% increase in the percentage change in tumor burden (i.e., taking sum of all the products of all the index lesions and any new lesions) when compared to SPD at nadir.

    Measured: Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10

  2. Time to Progression Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination Who Progress While on Treatment

    Time to Progression will be defined as the time from treatment initiation until the first documentation of progression as calculated by irRC in patients who show progression. Progression will be defined as at least a 25% increase percentage change in tumor burden (i.e., taking the sum of all the products of all index lesions and any new lesions) when compared to sum of all the products of diameters (SPD) at nadir.

    Measured: Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10

  3. Progression Free Survival (PFS) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination

    Median Progression Free Survival (mPFS) was estimated using a Kaplan-Meier curve with 0 censored patients. PFS is defined from the time of treatment initiation until the first documentation of progressive disease. Any patient without the event at the time of analysis will be censored from the last documented contact.

    Measured: Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10

  4. Overall Survival (OS) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination

    Overall Survival (OS) was estimated using a kaplan-meier curve with 0 patients censored. OS is defined from the time of treatment initiation until the time of death from any cause. Any patient without the event at the time of analysis will be censored from the last documented contact.

    Measured: Every 12 weeks during treatment with a 12 week induction and then 28 day maintenance cycles. Range of cycles completed (including induction cycle) 0-10

  5. Recovery of Tumor Immune Surveillance: T-cell Response to Defined Pancreatic Cancer Tumor Antigens

    Optional blood draws to analyze the inflammatory T cell function before, during and after treatment.

    Measured: Prior to ipilimumab infusion at weeks 1, 4, 7, and 10, and then every 12 weeks starting at week 13 where range of cycles including induction cycle was 0-10 (Induction cycle = 12 weeks, maintenance cycle = 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2011 (estimated)
  2. Study start11 Jun 2012
  3. Primary completion16 Oct 2014
  4. Study completion6 May 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Intervention model
Sequential
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01473940
Sponsor's protocol ID
NU 10I02
Other IDs
NCI-2011-03135, STU00045323
Status last verified
Feb 2020
First submitted
19 Oct 2011
Last updated
6 Mar 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ipilimumab, gemcitabine hydrochloride and laboratory biomarker analysis in people with Duct Cell Adenocarcinoma of the Pancreas and Recurrent Pancreatic Cancer, run by Northwestern University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Dose Limiting Toxicities (DLTs) Seen in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination in Order to Define the Maximum Tolerated Dose (MTD) (time frame: During the 12 weeks of Induction Therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01473940.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in