Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Recurrence

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

All Drugs and Chemicals

Antineoplastic Agents

Gastrointestinal Agents

Antibodies

Antibodies, Monoclonal

Gemcitabine

Ipilimumab

Immunoglobulins

Pancrelipase

Pancreatin

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Immunologic Factors

Antimetabolites

Immune Checkpoint Inhibitors

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.

ipilimumab

gemcitabine hydrochloride

laboratory biomarker analysis

Mary Mulcahy

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.

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.

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

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

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

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.

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.

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.

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.

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

Robert H. Lurie Cancer Center

Northwestern University

Mary Mulcahy, MD

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 12, 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.

Ipilimumab: Given IV

Gemcitabine hydrochloride: Given IV

Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg

Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg

Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg

Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

A 3 + 3 enrollment design was adopted to monitor safety and determine the MTD based on DLTs obsesved. The MTD is the highest dose at which 0 of 3 or 1 of 6 DLTs are detected. The MTD is exceeded if 2 of 3 or 2 of 6 DLTs are detected. There will be no dose escalation within a cohort.

The number of DLTs seen at each cohort were used to determine the MTD for the expansion cohort. The MTD was determined to be Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg

Number of DLTS seen in cohort

Number of AST increase DLTs seen in cohort

Number of diarrhea DLTs seen in cohort

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)

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

Cohort 2/Expansion Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg

PFS was considered to be a more meaningful outcome measure to report on. This outcome measure was so similar that it was considered duplicate information and data was not collected and analyzed specifically for this outcome measure.

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

Cohort 2 and expansion cohorts are combined for this outcome measure as they were both at the MTD doses.

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

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

Due to this being optional, insufficient samples were obtained and no data or analysis of blood was completed.

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

Duration of response is shown below for patients who showed a response as defined by immune-related response criteria (irCR) as either of the following:

irComplete Response (irCR)-Complete disappearance of all index lesions or 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)

Duration of response is defined as the time from first documentation of response to first documentation of progression, with progression defined as:

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 the sum of all the product diameters (SPD) at nadir.

Cohort 2 Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg

Expansion - Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg

Only patients with a response are shown here.

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

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Interventions

Study Description

Keywords

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Contact Details

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