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NCT00398086

Gemcitabine Plus Albumin-bound Paclitaxel In Patients With Advanced Metastatic Pancreatic Cancer

Completed Phase 1, PHASE2 Results posted Last updated 22 November 2019
What this trial tests

Phase 1, PHASE2 trial testing Gemcitabine in Metastatic Pancreatic Cancer in 67 participants. Completed in 1 December 2010.

Timeline
1 November 2006
Primary endpoint
1 September 2008
1 December 2010

Quick facts

Lead sponsorCelgene
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment67
Start date1 November 2006
Primary completion1 September 2008
Estimated completion1 December 2010
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Celgene — full company profile →

Who can join

18 and older, any sex, with Metastatic 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 Participants With Dose-limiting Toxicities Primary · Cycle 1 (Days 1-28)

A dose-limiting toxicity (DLT) is defined as one or more of the following toxicities related to study drug during Cycle 1, according to the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), Version 3: * Grade 4 neutropenia lasting \>3 days in the absence of growth factor support; * Grade 4 neutropenia associated with fever \>38.5°C; * Any other Grade 4 hematological toxicity; * Grade 3 thrombocytopenia with hemorrhage; * Grade 3 or 4 nausea, vomiting or diarrhea despite prophylaxis or treatment with an optimal anti-emetic or anti-diarrhea regimen; * Any othe

GroupValue95% CI
100 mg/m^24
125 mg/m^20
150 mg/m^21
Number of Participants With Adverse Events (AE) Secondary · Up to 25 months

An AE was any untoward medical occurrence, not necessarily having a causal relationship with the patient's treatment, that began or worsened in grade after the start of study drug through 30 days after the last dose. A serious AE (SAE) is any untoward medical occurrence that is fatal, life-threatening, results in persistent or significant disability or incapacity, requires or prolongs existing in-patient hospitalization, is a congenital anomaly/birth defect, or is a condition that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. Treatment-re

Patients with at least 1 AE
GroupValue95% CI
100 mg/m^220
125 mg/m^244
150 mg/m^23
At least 1 grade 3 or higher AE
GroupValue95% CI
100 mg/m^215
125 mg/m^242
150 mg/m^23
At least 1 treatment-related AE
GroupValue95% CI
100 mg/m^218
125 mg/m^242
150 mg/m^23
At least 1 treatment-related grade 3 to 5 AE
GroupValue95% CI
100 mg/m^211
125 mg/m^238
150 mg/m^23
Patients with at least 1 SAE
GroupValue95% CI
100 mg/m^210
125 mg/m^224
150 mg/m^21
Patients with at least 1 treatment-related SAE
GroupValue95% CI
100 mg/m^24
125 mg/m^212
150 mg/m^21
At least 1 AE and drug permanently discontinued
GroupValue95% CI
100 mg/m^23
125 mg/m^212
150 mg/m^22
At least 1 TRAE and drug permanently discontinued
GroupValue95% CI
100 mg/m^22
125 mg/m^28
150 mg/m^22
Percentage of Participants Who Achieved an Objective Confirmed Overall Response Secondary · Up to approximately 4 years

Overall Response is defined as the percent of participants who achieve an objective confirmed complete (CR) or partial response (PR). Response was determined according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, assessed by an Independent Radiological Reviewer. CR: The disappearance of all known disease and no new sites or disease-related symptoms confirmed at least 4 weeks after initial documentation. All sites must be assessed, including non-measurable sites, such as effusions, or markers. PR: At least a 30% decrease in the sum of the longest diameters of target le

GroupValue95% CI
100 mg/m^2258.7 – 49.1
125 mg/m^23924.2 – 53.0
150 mg/m^20NA – NA
Percentage of Participants With Disease Control Secondary · Up to approximately 4 years

Disease control is defined as participants with Stable Disease for at least 16 weeks, or confirmed complete or partial overall response, based on RECIST guidelines and assessed by an Independent Radiological Reviewer. Stable disease is defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for Progressive Disease, and no new non-target lesions or unequivocal progression of existing non-target lesions. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the small

GroupValue95% CI
100 mg/m^25533.2 – 76.8
125 mg/m^25539.8 – 69.3
150 mg/m^2330.8 – 90.6
Progression-free Survival Secondary · Up to approximately 4 years

Progression-free survival is defined as the time from first dose of study drug to the start of disease progression or patient death, whichever occurs first, assessed by an Independent Radiological Reviewer. Participants who do not have disease progression or have not died were censored at the last known time that the participant was progression free. Progression-free survival was summarized using Kaplan-Meier methods. Progressive Disease is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters re

GroupValue95% CI
100 mg/m^26.13.7 – NA
125 mg/m^26.94.8 – 9.2
150 mg/m^21.60.5 – 10.0
Duration of Response Secondary · Up to approximately 4 years

Duration of response was assessed by progression-free survival for participants who achieved a confirmed Complete Response or Partial Response, assessed by an Independent Radiological Reviewer.

GroupValue95% CI
100 mg/m^2NA2.4 – NA
125 mg/m^27.35.5 – 21.9
Overall Survival Secondary · Up to approximately 4 years

Overall survival was defined as the time from the date of first dose of study drug to the date of patient death from all causes. Participants who did not die were censored at the last known time the patient was alive. Patient survival was summarized using Kaplan-Meier methods.

GroupValue95% CI
100 mg/m^29.36.6 – 11.9
125 mg/m^212.28.9 – 17.9
150 mg/m^26.10.5 – 17.9
Maximal Degree of Myelosuppression Secondary · During the treatment phase, up to a maximum of 24 months.

The maximal degree of myelosuppression was assessed by the overall nadir of absolute neutrophil count (ANC), white blood cell count and platelet count based on clinical laboratory measurements.

Absolute neutrophil count
GroupValue95% CI
100 mg/m^21.38± 1.541
125 mg/m^20.96± 1.446
150 mg/m^20.47± 0.460
White blood cell count
GroupValue95% CI
100 mg/m^22.69± 1.734
125 mg/m^22.18± 1.849
150 mg/m^21.52± 1.484
Platelet count
GroupValue95% CI
100 mg/m^2120.3± 79.02
125 mg/m^288.3± 62.10
150 mg/m^258.7± 48.64
Maximal Degree of Anemia Secondary · During the treatment phase, up to a maximum of 24 months.

The maximal degree of anemia (and myelosuppression) was assessed by the overall (any time after first dose of study drug) nadir of hemoglobin levels based on clinical laboratory measurements.

GroupValue95% CI
100 mg/m^295.1± 12.85
125 mg/m^291.8± 10.43
150 mg/m^295.3± 15.37

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected up to 30 days after the last dose (a maximum of 25 months).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

100 mg/m^2
Serious: 10/20 (50%)
Deaths:
125 mg/m^2
Serious: 24/44 (55%)
Deaths:
150 mg/m^2
Serious: 1/3 (33%)
Deaths:

Serious adverse events (48 terms)

ReactionSystem100 mg/m^2125 mg/m^2150 mg/m^2
PyrexiaGeneral disorders
DehydrationMetabolism and nutrition disorders
PneumoniaInfections and infestations
BacteraemiaInfections and infestations
Gastrointestinal haemorrhageGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
PainGeneral disorders
PancytopeniaBlood and lymphatic system disorders
Neutropenic sepsisInfections and infestations
Abdominal wall abscessInfections and infestations
CellulitisInfections and infestations
Clostridium difficile colitisInfections and infestations
EndocarditisInfections and infestations
InfectionInfections and infestations
SepsisInfections and infestations
Urinary tract infectionInfections and infestations
DiarrhoeaGastrointestinal disorders
AscitesGastrointestinal disorders
Duodenal obstructionGastrointestinal disorders
Enterocutaneous fistulaGastrointestinal disorders
IleusGastrointestinal disorders
Ileus paralyticGastrointestinal disorders
NauseaGastrointestinal disorders
Obstruction gastricGastrointestinal disorders
Other adverse events (191 terms — click to expand)

ReactionSystem100 mg/m^2125 mg/m^2150 mg/m^2
FatigueGeneral disorders
AlopeciaSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
Neuropathy peripheralNervous system disorders
Oedema peripheralGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
RashSkin and subcutaneous tissue disorders
ConstipationGastrointestinal disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
LeukopeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
DysgeusiaNervous system disorders
DizzinessNervous system disorders
AnxietyPsychiatric disorders
InsomniaPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Mucosal inflammationGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ChillsGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
ErythemaSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Abdominal distensionGastrointestinal disorders
Neutrophil count decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Weight decreasedInvestigations
DepressionPsychiatric disorders
AstheniaGeneral disorders
Urinary tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations

Most-reported serious reactions: Pyrexia, Dehydration, Pneumonia, Bacteraemia, Gastrointestinal haemorrhage, Intestinal obstruction, Small intestinal obstruction, Pain.

Data from ClinicalTrials.gov NCT00398086 adverse events section.

Sponsor's own description

To determine the maximum tolerated dose and dose-limiting toxicity of Gemcitabine plus Albumin-bound paclitaxel (ABI-007) in patients with advanced metastatic pancreatic cancer.

Publications & conference data

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

  1. The pancreas cancer microenvironment.
    Feig C, Gopinathan A, Neesse A, Chan DS, et al · · 2012 · cited 1054× · PMID 22896693 · DOI 10.1158/1078-0432.ccr-11-3114
  2. Gemcitabine plus nab-paclitaxel is an active regimen in patients with advanced pancreatic cancer: a phase I/II trial.
    Von Hoff DD, Ramanathan RK, Borad MJ, Laheru DA, et al · · 2011 · cited 777× · PMID 21969517 · DOI 10.1200/jco.2011.36.5742
  3. The Paradoxical Web of Pancreatic Cancer Tumor Microenvironment.
    Lafaro KJ, Melstrom LG. · · 2019 · cited 67× · PMID 30558722 · DOI 10.1016/j.ajpath.2018.09.009
  4. Enhancing the Efficacy of CAR T Cells in the Tumor Microenvironment of Pancreatic Cancer.
    Henze J, Tacke F, Hardt O, Alves F, et al · · 2020 · cited 28× · PMID 32481570 · DOI 10.3390/cancers12061389
  5. Tailor-Made Nanomaterials for Diagnosis and Therapy of Pancreatic Ductal Adenocarcinoma.
    Hu X, Xia F, Lee J, Li F, et al · · 2021 · cited 27× · PMID 33854877 · DOI 10.1002/advs.202002545
  6. Context Matters: Response Heterogeneity to Collagen-Targeting Approaches in Desmoplastic Cancers.
    Fuller AM, Eisinger-Mathason TSK. · · 2022 · cited 8× · PMID 35804902 · DOI 10.3390/cancers14133132
  7. Looking to the future: biomarkers in the management of pancreatic adenocarcinoma.
    Spratlin JL, Mulder KE. · · 2011 · cited 8× · PMID 22016635 · DOI 10.3390/ijms12095895
  8. <sup>18</sup>F-FDG PET/CT response in a phase 1/2 trial of nab-paclitaxel plus gemcitabine for advanced pancreatic cancer.
    Korn RL, Von Hoff DD, Borad MJ, Renschler MF, et al · · 2017 · cited 4× · PMID 28774338 · DOI 10.1186/s40644-017-0125-5

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Trials by the same sponsor.

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