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NCT01298570

Regorafenib+FOLFIRI Versus Placebo+FOLFIRI as 2nd Line Tx in Metastatic Colorectal Cancer

Completed Phase 2 Results posted Last updated 6 January 2021
What this trial tests

Phase 2 trial testing Regorafenib (BAY 73-4506) in Colorectal Cancer Metastatic in 181 participants. Completed in 2 October 2020.

Timeline
7 April 2011
Primary endpoint
15 November 2016
2 October 2020

Quick facts

Lead sponsorUNC Lineberger Comprehensive Cancer Center
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment181
Start date7 April 2011
Primary completion15 November 2016
Estimated completion2 October 2020
Sites24 locations across Ireland, United States

Drugs / interventions tested

Conditions studied

Sponsor

UNC Lineberger Comprehensive Cancer Center — full company profile →

Who can join

18 and older, any sex, with Colorectal Cancer Metastatic. 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.

Progression Free Survival (PFS) Primary · 5.5 years

To compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients failing one prior oxaliplatin-containing regimen for metastatic colorectal cancer. PFS is defined as the time from randomization until metastatic colorectal cancer (mCRC) progression or death as a result of any cause. Radiographic response will be measured by RECIST, Response Evaluation Criteria In Solid Tumors Criteria, indicating if subject experienced a Complete Response (CR), disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diam

GroupValue95% CI
Arm A6.15.5 – 7.3
Arm B5.34.1 – 6.0
Overall Response(OR)Rate Secondary · 3 years

To compare overall response (OR) rates (OR= CR + PR) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

GroupValue95% CI
Arm A0
Arm B0
Arm A35
Arm B12
Arm A67
Arm B46
Disease Control (DC) Rate Secondary · 3 years

To compare Disease Control (DC) Rate (DC= CR + PR + SD) between ARM A and ARM B as defined via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions and Stable Disease (SD) ), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the

GroupValue95% CI
Arm A84
Arm B43
Arm A18
Arm B15
Overall Survival (OS) Secondary · 5.5 years

To compare overall survival (OS) between ARM A and ARM B. OS is defined as the time from randomization until death as a result of any cause.

GroupValue95% CI
Arm A13.810.5 – 14.8
Arm B11.79.0 – 15.9
Drug Metabolism Secondary · 28 days

To compare the pharmacokinetic (PK) profile of FOLFIRI between a subset of patients receiving regorafenib (ARM A) and patients receiving placebo (Arm B). The Area Under the Curve (AUC) levels of the irinotecan metabolite SN-38 were compared.

Cycle 1
GroupValue95% CI
Arm A0.680.49 – 0.89
Arm B0.630.47 – 0.91
Cycle 2
GroupValue95% CI
Arm A0.590.24 – 0.85
Arm B0.720.47 – 0.91
Percentage of Patients With Severe Adverse Events Secondary · 3 years

Toxicity Assessments were made according to NCI CTCAE v. 4.0 . Severe events (grades 3-4) that occurred in a higher percentage of regorafenib treated participants as compared to placebo are reported below.

neutropenia
GroupValue95% CI
Arm A41
Arm B30
diarrhea
GroupValue95% CI
Arm A15
Arm B5
hypophosphatemia
GroupValue95% CI
Arm A14
Arm B0
hypertension
GroupValue95% CI
Arm A8
Arm B2
elevated lipase
GroupValue95% CI
Arm A8
Arm B3

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A
Serious: 60/120 (50%)
Deaths: 112/120
Arm B
Serious: 20/61 (33%)
Deaths: 59/61

Serious adverse events (91 terms)

ReactionSystemArm AArm B
DiarrheaGastrointestinal disorders
Abdominal painGastrointestinal disorders
FeverGeneral disorders
Febrile neutropeniaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
DehydrationMetabolism and nutrition disorders
Rectal hemorrhageGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
CholecystitisHepatobiliary disorders
DyspneaRespiratory, thoracic and mediastinal disorders
IleusGastrointestinal disorders
Mucositis oralGastrointestinal disorders
Thromboembolic eventVascular disorders
Chest pain - cardiacCardiac disorders
ConstipationGastrointestinal disorders
Death NOSGeneral disorders
FatigueGeneral disorders
FallInjury, poisoning and procedural complications
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Lung infectionInfections and infestations
Platelet count decreasedInvestigations
SepsisInfections and infestations
Soft tissue infectionInfections and infestations
Other adverse events (71 terms — click to expand)

ReactionSystemArm AArm B
FatigueGeneral disorders
Neutrophil count decreasedInvestigations
AnemiaBlood and lymphatic system disorders
Mucositis oralGastrointestinal disorders
DiarrheaGastrointestinal disorders
NauseaGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Abdominal painGastrointestinal disorders
ConstipationGastrointestinal disorders
HypokalemiaMetabolism and nutrition disorders
VomitingGastrointestinal disorders
HypophosphatemiaMetabolism and nutrition disorders
HypoalbuminemiaMetabolism and nutrition disorders
Alkaline phosphatase increasedInvestigations
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
White blood cell decreasedInvestigations
Platelet count decreasedInvestigations
Alanine aminotransferase increasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
HypocalcemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Peripheral sensory neuropathyNervous system disorders
Weight lossInvestigations
PainGeneral disorders
HypertriglyceridemiaMetabolism and nutrition disorders
HeadacheNervous system disorders
HypertensionVascular disorders
Blood bilirubin increasedInvestigations
DyspneaRespiratory, thoracic and mediastinal disorders
Lipase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
FeverGeneral disorders
ProteinuriaRenal and urinary disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HyperglycemiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
Serum amylase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DehydrationMetabolism and nutrition disorders
Dry skinSkin and subcutaneous tissue disorders

Most-reported serious reactions: Diarrhea, Abdominal pain, Fever, Febrile neutropenia, Neutrophil count decreased, Dehydration, Rectal hemorrhage, Anemia.

Data from ClinicalTrials.gov NCT01298570 adverse events section.

Sponsor's own description

This randomized (2:1), multi-center, placebo-controlled, phase II efficacy study is designed to compare PFS between regorafenib + FOLFIRI chemotherapy (ARM A) versus placebo + FOLFIRI (ARM B) in patients with mCRC previously treated with a FOLFOX regimen.

Publications & conference data

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

  1. Molecular insight of regorafenib treatment for colorectal cancer.
    Arai H, Battaglin F, Wang J, Lo JH, et al · · 2019 · cited 133× · PMID 31715423 · DOI 10.1016/j.ctrv.2019.101912
  2. Targeting the RAS oncogene.
    Takashima A, Faller DV. · · 2013 · cited 95× · PMID 23360111 · DOI 10.1517/14728222.2013.764990
  3. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study.
    Schultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, et al · · 2013 · cited 71× · PMID 23493136 · DOI 10.1093/annonc/mdt056
  4. Angiogenesis Inhibitors for Colorectal Cancer. A Review of the Clinical Data.
    Hansen TF, Qvortrup C, Pfeiffer P. · · 2021 · cited 34× · PMID 33804554 · DOI 10.3390/cancers13051031
  5. Regorafenib in gastrointestinal stromal tumors: clinical evidence and place in therapy.
    Ferraro D, Zalcberg J. · · 2014 · cited 23× · PMID 25342989 · DOI 10.1177/1758834014544892
  6. Anti-angiogenic therapies for metastatic colorectal cancer: current and future perspectives.
    Marques I, Araújo A, de Mello RA. · · 2013 · cited 20× · PMID 24307789 · DOI 10.3748/wjg.v19.i44.7955
  7. Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors.
    Jang JY, Kim D, Kim ND. · · 2023 · cited 18× · PMID 37176164 · DOI 10.3390/ijms24098457
  8. Regorafenib with a fluoropyrimidine for metastatic colorectal cancer after progression on multiple 5-FU-containing combination therapies and regorafenib monotherapy.
    Marks EI, Tan C, Zhang J, Zhou L, et al · · 2015 · cited 16× · PMID 26561209 · DOI 10.1080/15384047.2015.1113355

Verify or expand the search:

Other trials of Regorafenib (BAY 73-4506)

Trials testing the same drug.

Other recruiting trials for Colorectal Cancer Metastatic

Currently open trials in the same condition.

Other UNC Lineberger Comprehensive Cancer Center trials

Trials by the same sponsor.

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