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NCT00326495

BAY 43-9006 Plus Cetuximab to Treat Colorectal Cancer

Completed Phase 2 Results posted Last updated 24 July 2017
What this trial tests

Phase 2 trial testing Cetuximab in Metastatic Colorectal Cancer in 51 participants. Completed in 7 November 2014.

Timeline
10 May 2006
Primary endpoint
5 November 2014
7 November 2014

Quick facts

Lead sponsorNational Cancer Institute (NCI)
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment51
Start date10 May 2006
Primary completion5 November 2014
Estimated completion7 November 2014
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Metastatic Colorectal 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 Rate of Response Primary · 4 months

Rate of response is defined as the percentage of participants with a complete response (CR) + partial response (PR) + stable disease (SD) for 4 months. Response is defined by the Response is determined by the Response Evaluation Criteria in Solid Tumors (RECIST). Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Complete response is a disappearance of all target lesions. Stable disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (progressive disease), ta

GroupValue95% CI
BAY 43-9006 & Cetuximab15
Count of Participants With Adverse Events Secondary · 96 months, 26 days

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

GroupValue95% CI
BAY 43-9006 & Cetuximab50

Adverse events — posted to ClinicalTrials.gov

Time frame: 96 months, 26 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

BAY 43-9006 & Cetuximab
Serious: 22/50 (44%)
Deaths: 2/50

Serious adverse events (31 terms)

ReactionSystemBAY 43-9006 & Cetuximab
Small intestinal obstructionGastrointestinal disorders
FeverGeneral disorders
Abdominal distensionGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
Bladder infectionInfections and infestations
Death NOSGeneral disorders
HeadacheNervous system disorders
VomitingGastrointestinal disorders
AnaphylaxisImmune system disorders
Back painMusculoskeletal and connective tissue disorders
Blood bilirubin increasedInvestigations
Catheter related infectionInfections and infestations
ChillsGeneral disorders
DehydrationGastrointestinal disorders
DiarrheaGastrointestinal disorders
Duodenal obstructionGastrointestinal disorders
HematuriaRenal and urinary disorders
HypokalemiaMetabolism and nutrition disorders
HyponatremiaMetabolism and nutrition disorders
IleusGastrointestinal disorders
Ischemia cerebrovascularNervous system disorders
Lipase increasedInvestigations
Movements involuntaryNervous system disorders
NauseaGastrointestinal disorders
PainGeneral disorders
Other adverse events (144 terms — click to expand)

ReactionSystemBAY 43-9006 & Cetuximab
HypoalbuminemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Rash acneiformSkin and subcutaneous tissue disorders
HypophosphatemiaMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Lymphocyte count decreasedInvestigations
DiarrheaGastrointestinal disorders
Alkaline phosphatase increasedInvestigations
HyponatremiaMetabolism and nutrition disorders
HypomagnesemiaMetabolism and nutrition disorders
AnemiaBlood and lymphatic system disorders
FatigueGeneral disorders
HeadacheNervous system disorders
Blood bilirubin increasedInvestigations
NauseaGastrointestinal disorders
Platelet count decreasedInvestigations
Rash maculo-papularSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
Dry skinSkin and subcutaneous tissue disorders
Palmar-plantar erythrodysesthesia syndromeSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
FeverGeneral disorders
Activated partial thromboplastin time prolongedInvestigations
HypokalemiaMetabolism and nutrition disorders
HypertensionVascular disorders
White blood cell decreasedInvestigations
Abdominal painGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
Mucositis oralGastrointestinal disorders
Weight lossInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
HypocalcemiaMetabolism and nutrition disorders
ChillsGeneral disorders
HypercalcemiaMetabolism and nutrition disorders
Voice alterationRespiratory, thoracic and mediastinal disorders
HypermagnesemiaMetabolism and nutrition disorders
CPK increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Small intestinal obstruction, Fever, Abdominal distension, Anemia, Bladder infection, Death NOS, Headache, Vomiting.

Data from ClinicalTrials.gov NCT00326495 adverse events section.

Sponsor's own description

Background: * Colorectal cancer (CRC) is a major public health problem in the U.S. and worldwide, and 5-year survival with widespread metastatic disease is less than 5%. * Expression of epidermal growth factor receptor (EGFR) or up-regulation of the gene occurs in the majority of CRC cases (60-80%). * Therapies targeting EGFR, like cetuximab, have shown activity in the treatment of solid tumors like CRC. * Cetuximab is FDA (Food and Drug Administration) approved for the treatment of EGFR-expressing CRC, but clinical responses to cetuximab are seen in only 10% of EGFR-expressing CRC. * One possible mechanism of resistance to cetuximab could be KRAS (Kirsten rat sarcoma) mutations. * Another major pathway implicated in colon carcinogenesis is the vascular endothelial growth factor (VEGF) pathway, which is involved in angiogenesis and is a validated target for therapy in CRC. * BAY 43-9006 is both a Raf kinase inhibitor and an inhibitor of VEGF receptor (VEGFR2) tyrosine kinase. * We hypothesize that the combined inhibition of EGFR, VEGFR2, and the Ras-(rapidly accelerated fibrosarcoma) Raf pathway will demonstrate promising clinical activity in CRC. Furthermore, in patients with mutant KRAS, combination of cetuximab with a drug that inhibits Raf kinase and acts downstream of Ras mutations, could restore tumor sensitivity to cetuximab. Objectives: * To determine the rate of response (complete response (CR) + partial response (PR) + stable disease (SD) for 4 months) and toxicity profile of combination of BAY 43-9006 and cetuximab in previously treated EGFR-expressing metastatic CRC in patients with mutant KRAS. * To evaluate BAY 43-9006 pharmacokinetics \& pharmacogenomics (CYP3A4/5 (cytochrome P450 3A4/5)). * To evaluate for this combination treatment pharmacodynamics, effect on tumor vascularity and effect on angiogenic cytokines. Eligibility: * Adults with histologically or cytologically documented, measurable, EGFR-expressing metastatic CRC, which has recurred or progressed following at least one prior 5FU (Fluorouracil)-based combination chemotherapy regimen administered for the treatment of metastatic disease. * Patients must be KRAS mutation-positive. Design: * BAY 43-9006 will be administered 400 mg by mouth twice daily * Cetuximab will be administered as 400 mg/m\^2 loading dose (week 1) followed by 250 mg/m\^2 IV (intravenous) weekly. * If procedure may be performed safely, tumor biopsy will be obtained prior to treatment and after 4 weeks of treatment. * Optional positron emission tomography (PET)/computerized tomography (CT) imaging with 89Zr-labeled, EGFR-targeting antibody panitumumab may be performed to evaluate radiation dosimetry, safety, and tumor distribution prior to and following treatment with study agents. * Patients will be evaluated for response every 8 weeks using the RECIST (Response Evaluation Criteria in Solid Tumors) criteria. * This trial uses a phase II optimal design targeting a response rate as defined above of 20% in patients with mutant KRAS. Up to 49 patients may be treated.

Publications & conference data

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

  1. Ras in cancer and developmental diseases.
    Fernández-Medarde A, Santos E. · · 2011 · cited 601× · PMID 21779504 · DOI 10.1177/1947601911411084
  2. Current and emerging therapeutic approaches for colorectal cancer: A comprehensive review.
    Kumar A, Gautam V, Sandhu A, Rawat K, et al · · 2023 · cited 159× · PMID 37206081 · DOI 10.4240/wjgs.v15.i4.495
  3. Recent progress on vascular endothelial growth factor receptor inhibitors with dual targeting capabilities for tumor therapy.
    Liu Y, Li Y, Wang Y, Lin C, et al · · 2022 · cited 113× · PMID 35799213 · DOI 10.1186/s13045-022-01310-7
  4. Biomarkers in precision therapy in colorectal cancer.
    Reimers MS, Zeestraten EC, Kuppen PJ, Liefers GJ, et al · · 2013 · cited 64× · PMID 24759962 · DOI 10.1093/gastro/got022
  5. Therapy for Cancer: Strategy of Combining Anti-Angiogenic and Target Therapies.
    Comunanza V, Bussolino F. · · 2017 · cited 62× · PMID 29270405 · DOI 10.3389/fcell.2017.00101
  6. Interplay of Ferroptosis and Cuproptosis in Cancer: Dissecting Metal-Driven Mechanisms for Therapeutic Potentials.
    Wang J, Li J, Liu J, Chan KY, et al · · 2024 · cited 33× · PMID 38339263 · DOI 10.3390/cancers16030512
  7. Dosimetry and first human experience with <sup>89</sup>Zr-panitumumab.
    Lindenberg L, Adler S, Turkbey IB, Mertan F, et al · · 2017 · cited 31× · PMID 28913158
  8. 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

Verify or expand the search:

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00326495.

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