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NCT00844649

Phase III Study of ABI-007(Albumin-bound Paclitaxel) Plus Gemcitabine Versus Gemcitabine in Metastatic Adenocarcinoma of the Pancreas

Completed Phase 3 Results posted Last updated 25 November 2019
What this trial tests

Phase 3 trial testing Albumin-bound paclitaxel (ABI-007) in Metastatic Pancreatic Cancer in 861 participants. Completed in 9 April 2013.

Timeline
1 March 2009
Primary endpoint
17 September 2012
9 April 2013

Quick facts

Lead sponsorCelgene
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment861
Start date1 March 2009
Primary completion17 September 2012
Estimated completion9 April 2013
Sites193 locations across France, Italy, Russia, Ukraine, Belgium, Austria, Germany, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Celgene — full company profile →

Who can join

Adults 18 to 79, 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.

Overall Survival (OS) Primary · From randomization to death; until the data cut off 17 Sept 2012. The maximum time in follow up was 37 months.

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

GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine8.57.89 – 9.53
Gemcitabine6.76.01 – 7.23
Progression-free Survival (PFS) by Independent Radiological Review (IRR) Secondary · Randomization until disease progression or death from any cause; Until the data cut off of 17 Sept 2012. The maximum time in follow up was 37 months.

Progression-free survival was defined as the time from the date of randomization to the date of disease progression, or death (any cause) on or prior to the clinical cutoff date, whichever occurred earlier. Participants who did not have disease progression or had not died were censored at the date of the last tumor assessment, on or prior to the clinical cutoff, and the patient was progression free. If a patient began a new anti-cancer treatment prior to documented disease progression (or death), the patient was censored at the date of last assessment when the patient was documented as progres

GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine5.54.47 – 5.95
Gemcitabine3.73.61 – 4.04
Percentage of Participants Who Achieved an Objective Confirmed Overall Response by Independent Radiological Review (IRR) Secondary · Assessment every 4 weeks after initial response; Day 1 to data cut off of 17 Sept 2013; maximum time on study 37 months

Objective tumor response was summarized as the percentage of participants who achieved a confirmed complete (CR) or partial response (PR) based on an independent blinded radiology assessment of response using Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Using RECIST Version 1.0, participants were to achieve either a complete response (CR) defined as the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation or partial response (PR) defined as at least a 30% decrease in the sum of the longest di

GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine2319.1 – 27.2
Gemcitabine75.0 – 10.1
Participants With Treatment Emergent Adverse Events (AE) Secondary · Study drug initiation through 30 days after the last dose of study drug or EOS, whichever is later; Up to 696 days

A Treatment Emergent Adverse Event (TEAE) is as any AE occurring or worsening on or after the first treatment of any study drug, and within 30 days after the last dose of the last study drug. Severity grades according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on a 1-5 scale: Grade 1= Mild AE, Grade 2= Moderate AE, Grade 3= Severe AE, Grade 4= Life-threatening or disabling AE, Grade 5=Death related to AE.

At least 1 AE
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine417
Gemcitabine395
≥ 1 Treatment related AE (TEAE)
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine403
Gemcitabine371
At least 1 Serious Adverse Event (SAE)
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine212
Gemcitabine172
≥ 1 treatment related SAE
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine121
Gemcitabine53
≥ 1 Grade (GR) 3/4 AE
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine370
Gemcitabine298
≥ 1 Grade 3 or higher AE
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine374
Gemcitabine303
≥ 1 AE leading to stopping treatment
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine149
Gemcitabine95
≥ 1 AE leading to death
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine18
Gemcitabine18
Number of Participants With Dose Reductions Secondary · Maximum time on treatment was 666 days

The number of participants with dose reductions occurring during the treatment period. Dose reductions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

At least 1 alumbin bound paclitaxel dose reduction
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine (Gem)172
Gemcitabine (Gem)0
At least 1 Gemcitabine dose reduction
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine (Gem)198
Gemcitabine (Gem)132
Number of Participants With Dose Interruptions Secondary · Maximum time on treatment was 666 days

The number of participants with dose interruptions experienced by participants that occurred during the treatment period. Dose interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities.

≥ 1 Albumin-bound paclitaxel dose interruption
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine2
Gemcitabine0
At least 1 Gemcitabine dose interruption
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine8
Gemcitabine9
Number of Participants With Dose Delays/Doses Not Given Secondary · Up to 666 days

The number of dose delays or doses not given experienced by participants during the treatment period. Dose delays are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities. Treatment delays of no longer than 21 days allowed participants to recover from acute toxicity, otherwise participants were discontinued from further treatment except in the event of peripheral neuropathy.

At least 1 ABI-007 dose delay/Not given
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine300
Gemcitabine0
At least ≥ 1 Gem dose delay/Not given
GroupValue95% CI
Albumin-bound Paclitaxel (ABI-007)/Gemcitabine295
Gemcitabine230

Adverse events — posted to ClinicalTrials.gov

Time frame: Day 1 up to 30 days after the last dose (a maximum of 666 days). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Albumin-bound Paclitaxel (ABI-007)/Gemcitabine
Serious: 212/421 (50%)
Deaths:
Gemcitabine
Serious: 172/402 (43%)
Deaths:

Serious adverse events (232 terms)

ReactionSystemAlbumin-bound Paclitaxel (…Gemcitabine
PyrexiaGeneral disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
DehyrationMetabolism and nutrition disorders
VomitingGastrointestinal disorders
PneumoniaInfections and infestations
Deep vein thrombosisVascular disorders
Abdominal PainGastrointestinal disorders
NauseaGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
CholangitisHepatobiliary disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
CellulitisInfections and infestations
Pleural effusionRespiratory, thoracic and mediastinal disorders
Urinary Tract InfectionInjury, poisoning and procedural complications
Oedema peripheralGeneral disorders
ConstipationGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
AscitesGastrointestinal disorders
SepsisInfections and infestations
Septic ShockInfections and infestations
AstheniaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Decreased AppetiteMetabolism and nutrition disorders
Cerebrovascular accidentNervous system disorders
Other adverse events (60 terms — click to expand)

ReactionSystemAlbumin-bound Paclitaxel (…Gemcitabine
FatigueGeneral disorders
NauseaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
VomitingGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
RashSkin and subcutaneous tissue disorders
Neuropathy peripheralNervous system disorders
Peripheral sensory neuropathyNervous system disorders
Abdominal PainGastrointestinal disorders
AstheniaGeneral disorders
DehydrationMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DysgeusiaNervous system disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
InsomniaPsychiatric disorders
HeadacheNervous system disorders
LeukopeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
HypokalemiaMetabolism and nutrition disorders
DepressionPsychiatric disorders
ChillsGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Alanine aminotransferase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
AnxietyPsychiatric disorders
Mucosal inflammationGeneral disorders
Abdominal pain upperGastrointestinal disorders
Haemoglobin decreasedInvestigations
Back PainMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedInvestigations

Most-reported serious reactions: Pyrexia, Pulmonary embolism, Dehyration, Vomiting, Pneumonia, Deep vein thrombosis, Abdominal Pain, Nausea.

Data from ClinicalTrials.gov NCT00844649 adverse events section.

Sponsor's own description

Phase III Metastatic Pancreatic Cancer

Publications & conference data

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

  1. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine.
    Von Hoff DD, Ervin T, Arena FP, Chiorean EG, et al · · 2013 · cited 4837× · PMID 24131140 · DOI 10.1056/nejmoa1304369
  2. Pancreatic cancer.
    Vincent A, Herman J, Schulick R, Hruban RH, et al · · 2011 · cited 2121× · PMID 21620466 · DOI 10.1016/s0140-6736(10)62307-0
  3. JAK-STAT Signaling: A Double-Edged Sword of Immune Regulation and Cancer Progression.
    Owen KL, Brockwell NK, Parker BS. · · 2019 · cited 493× · PMID 31842362 · DOI 10.3390/cancers11122002
  4. The impact of cancer-associated fibroblasts on major hallmarks of pancreatic cancer.
    Sun Q, Zhang B, Hu Q, Qin Y, et al · · 2018 · cited 154× · PMID 30429887 · DOI 10.7150/thno.26546
  5. NALIRIFOX, FOLFIRINOX, and Gemcitabine With Nab-Paclitaxel as First-Line Chemotherapy for Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis.
    Nichetti F, Rota S, Ambrosini P, Pircher C, et al · · 2024 · cited 80× · PMID 38190183 · DOI 10.1001/jamanetworkopen.2023.50756
  6. Consensus, debate, and prospective on pancreatic cancer treatments.
    Wang J, Yang J, Narang A, He J, et al · · 2024 · cited 56× · PMID 39390609 · DOI 10.1186/s13045-024-01613-x
  7. Second-line therapy after nab-paclitaxel plus gemcitabine or after gemcitabine for patients with metastatic pancreatic cancer.
    Chiorean EG, Von Hoff DD, Tabernero J, El-Maraghi R, et al · · 2016 · cited 56× · PMID 27351217 · DOI 10.1038/bjc.2016.185
  8. Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies.
    Abdel-Rahman O. · · 2019 · cited 46× · PMID 30465184 · DOI 10.1007/s12094-018-1992-3

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