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NCT01473940

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

Completed Phase 1 Results posted Last updated 6 March 2020
What this trial tests

Phase 1 trial testing ipilimumab in Duct Cell Adenocarcinoma of the Pancreas in 21 participants. Completed in 6 May 2018.

Timeline
11 June 2012
Primary endpoint
16 October 2014
6 May 2018

Quick facts

Lead sponsorNorthwestern University
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Designsequential
Maskingnone
Primary purposetreatment
Enrollment21
Start date11 June 2012
Primary completion16 October 2014
Estimated completion6 May 2018
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Duct Cell Adenocarcinoma of the Pancreas or Recurrent Pancreatic Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · During the 12 weeks of Induction Therapy

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

Number of DLTS seen in cohort
GroupValue95% CI
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg0
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg0
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg2
Number of AST increase DLTs seen in cohort
GroupValue95% CI
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg0
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg0
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg1
Number of diarrhea DLTs seen in cohort
GroupValue95% CI
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg0
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg0
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg1
Response Rate Using Immune-related Response Criteria (irRC) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination Secondary · 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

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 o

GroupValue95% CI
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg0
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg0
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg0
Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg0
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg0
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg1
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg1
Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg1
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg2
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg0
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg3
Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg2
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg1
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg3
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg1
Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg3
Progression Free Survival (PFS) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination Secondary · 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

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.

GroupValue95% CI
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg3.38592.5970 – 8.0868
Cohort 2/Expansion Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg2.53120.7890 – 4.8323
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg3.86260.7561 – 22.4195
Overall Survival (OS) in Patients With Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination Secondary · 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

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.

GroupValue95% CI
Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg5.32545.0953 – 9.5661
Cohort 2/Expansion Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg5.71991.6108 – 22.8139
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg8.99080.7561 – 30.0460
Duration of Response in Patients Pancreas Adenocarcinoma Treated With Ipilimumab and Gemcitabine Combination Secondary · From the time of response and 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

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 Di

GroupValue95% CI
Cohort 2 Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg8.5
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg19.8
Expansion - Gemcitabine-1,000mg/m2+Ipilimumab-3mg/kg11

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse Events were collected from the time of treatment initiation until treatment discontinuation for any reason. Treatment was considered to be one induction cycle of 12 weeks followed by 28 day maintenance cycles with the range of cycles completed by any patients 0-10 (including the induction cycle). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort 1 Gemcitabine - 750 mg/m2, Ipilimumab 3 mg/kg
Serious: 2/3 (67%)
Deaths: 3/3
Cohort 2 Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg
Serious: 3/4 (75%)
Deaths: 4/4
Cohort 3 Gemcitabine -1,000 mg/m2, Ipilimumab 6 mg/kg
Serious: 4/6 (67%)
Deaths: 6/6
Expansion Cohort Gemcitabine - 1,000 mg/m2, Ipilimumab 3 mg/kg
Serious: 5/8 (63%)
Deaths: 8/8

Serious adverse events (23 terms)

ReactionSystemCohort 1 Gemcitabine - 750…Cohort 2 Gemcitabine - 1,0…Cohort 3 Gemcitabine -1,00…Expansion Cohort Gemcitabi…
Duodenal ObstructionGastrointestinal disorders
Catheter-related InfectionInfections and infestations
DiarrheaGastrointestinal disorders
SepsisInfections and infestations
VomitingGastrointestinal disorders
AscitesGastrointestinal disorders
Abdominal painGastrointestinal disorders
Bilirubin IncreasedInvestigations
Sepsis resulting in deathInfections and infestations
DiarrheaGastrointestinal disorders
FallInjury, poisoning and procedural complications
Back PainMusculoskeletal and connective tissue disorders
NauseaGastrointestinal disorders
Gastric hemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
SepsisInfections and infestations
ColitisGastrointestinal disorders
Abdominal PainGastrointestinal disorders
Facial Muscle WeaknessNervous system disorders
Death due to diseaseNeoplasms benign, malignant and unspecified (incl cysts and polyps)
VomitingGastrointestinal disorders
HypertensionVascular disorders
Hemolytic Uremic SyndromeBlood and lymphatic system disorders
Other adverse events (106 terms — click to expand)

ReactionSystemCohort 1 Gemcitabine - 750…Cohort 2 Gemcitabine - 1,0…Cohort 3 Gemcitabine -1,00…Expansion Cohort Gemcitabi…
AnemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Alkaline Phosphatase IncreasedInvestigations
Aspartate Aminotransferase IncreasedInvestigations
Platelet Count DecreasedInvestigations
HyperglycemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
Lymphocyte Count DecreasedInvestigations
Neutrophil Count DecreasedInvestigations
White Blood Cell DecreasedInvestigations
Abdominal PainGastrointestinal disorders
DiarrheaGastrointestinal disorders
FeverGeneral disorders
Alanine Aminotransferase IncreasedInvestigations
AnorexiaMusculoskeletal and connective tissue disorders
HypocalcemiaMetabolism and nutrition disorders
Sinus TachycardiaCardiac disorders
Blood Bilirubin IncreasedInvestigations
Creatinine IncreasedInvestigations
INR IncreasedInvestigations
HypokalemiaMetabolism and nutrition disorders
HeadachesNervous system disorders
Peripheral Sensory NeuropathyNervous system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
HypertensionVascular disorders
Abdominal distensionGastrointestinal disorders
Dry MouthGastrointestinal disorders
VomitingGastrointestinal disorders
ChillsGeneral disorders
Flu-like SymptomsGeneral disorders
PainGeneral disorders
Weight LossInvestigations
HypercalcemiaMetabolism and nutrition disorders
Back PainMusculoskeletal and connective tissue disorders
DysgeusiaNervous system disorders
InsominaPsychiatric disorders
Maculo-papular RashSkin and subcutaneous tissue disorders

Most-reported serious reactions: Duodenal Obstruction, Catheter-related Infection, Diarrhea, Sepsis, Vomiting, Ascites, Abdominal pain, Bilirubin Increased.

Data from ClinicalTrials.gov NCT01473940 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Tumor microenvironment participates in metastasis of pancreatic cancer.
    Ren B, Cui M, Yang G, Wang H, et al · · 2018 · cited 442× · PMID 30060755 · DOI 10.1186/s12943-018-0858-1
  2. Pancreatic Ductal Adenocarcinoma: Current and Evolving Therapies.
    Adamska A, Domenichini A, Falasca M. · · 2017 · cited 429× · PMID 28640192 · DOI 10.3390/ijms18071338
  3. At the bedside: CTLA-4- and PD-1-blocking antibodies in cancer immunotherapy.
    Callahan MK, Wolchok JD. · · 2013 · cited 246× · PMID 23667165 · DOI 10.1189/jlb.1212631
  4. Current and future immunotherapeutic approaches in pancreatic cancer treatment.
    Farhangnia P, Khorramdelazad H, Nickho H, Delbandi AA. · · 2024 · cited 153× · PMID 38835055 · DOI 10.1186/s13045-024-01561-6
  5. Immune Checkpoint Inhibition for Pancreatic Ductal Adenocarcinoma: Current Limitations and Future Options.
    Kabacaoglu D, Ciecielski KJ, Ruess DA, Algül H. · · 2018 · cited 152× · PMID 30158932 · DOI 10.3389/fimmu.2018.01878
  6. Ipilimumab and Gemcitabine for Advanced Pancreatic Cancer: A Phase Ib Study.
    Kamath SD, Kalyan A, Kircher S, Nimeiri H, et al · · 2020 · cited 151× · PMID 31740568 · DOI 10.1634/theoncologist.2019-0473
  7. Mechanisms of T-Cell Exhaustion in Pancreatic Cancer.
    Saka D, Gökalp M, Piyade B, Cevik NC, et al · · 2020 · cited 106× · PMID 32823814 · DOI 10.3390/cancers12082274
  8. Perspectives in the treatment of pancreatic adenocarcinoma.
    Cid-Arregui A, Juarez V. · · 2015 · cited 106× · PMID 26309356 · DOI 10.3748/wjg.v21.i31.9297

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