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NCT03542877

Investigating Cabozantinib in Patients With Refractory Metastatic Colorectal Cancer

Completed Phase 2 Results posted Last updated 15 July 2022
What this trial tests

Phase 2 trial testing Oral Tablet: Cabozantinib in Colorectal Cancer in 44 participants. Completed in 7 March 2022.

Timeline
1 June 2018
Primary endpoint
19 October 2020
7 March 2022

Quick facts

Lead sponsorAcademic Thoracic Oncology Medical Investigators Consortium
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment44
Start date1 June 2018
Primary completion19 October 2020
Estimated completion7 March 2022
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Academic Thoracic Oncology Medical Investigators Consortium

Who can join

Adults 18 to 99, any sex, with 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.

12-Week Progression Free Survival Primary · This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.

A patient is classified as progression-free if s/he is assessed as not having progressive disease (PD) as defined per RECIST 1.1 criteria at either the 12-week assessment or after having at least 11 weeks of treatment for subjects without the 12-week assessment. Censored patients (i.e. those who have not progressed but who are missing a 12-week assessment) are not included in the analysis. Subjects who didn't have the 12-week assessment but who had clinical progression were included and considered to have progressed. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) for t

GroupValue95% CI
Oral Cabozantinib18
12-Week Progression-Free Survival by RAS Mutation Status Secondary · This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.

This has the same outcome measure description as the primary analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) 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
RAS Mutant7
RAS Wild Type11
12-Week Progression-Free Survival by PIK3CA Mutation Status Secondary · This outcome was assessed at the 12-week assessment. Subjects without the 12-week assessment but who had at least 11 weeks of treatment were included.

This has the same outcome measure description as the primary analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) 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
PIK3CA Mutant3
PIK3CA Wild Type11
Progression-Free Survival (PFS) Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

Progression-free survival will be defined as the time from administration of the initial dose of cabozantinib to evidence of radiographic progression as defined by RECIST criteria or death from any cause without evidence of disease progression, whichever occurs first. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) 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
Oral Cabozantinib139 – 21
Progression-Free Survival (PFS) by RAS Mutation Status Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

This has the same outcome measure description as the PFS analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) 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
RAS Mutant126 – 14
RAS Wild Type219 – 48
Progression-Free Survival (PFS) by PIK3CA Mutation Status Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

This has the same outcome measure description as the PFS analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECISTv1.0) 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
PIK3CA Mutant265 – NA
PIK3CA Wild Type206 – 29
Response Rate in Patients With CRC Treated With Cabozantinib Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

\*A patient is classified as a responder if s/he is assessed as having complete response or partial response (CR or PR) at the time of any assessment, where CR and PR are defined per RECIST 1.1 criteria.

GroupValue95% CI
Oral Cabozantinib1
Overall Survival (OS) in Patients With CRC Treated With Cabozantinib Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

Overall Survival will be defined as the time from administration of the initial dose of cabozantinib until death from any cause.

GroupValue95% CI
Oral Cabozantinib3624 – 50
Overall Survival (OS) by RAS Mutation Status Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

This has the same outcome measure description as the OS analysis.

GroupValue95% CI
RAS Mutant3018 – 46
RAS Wild Type4520 – NA
Overall Survival (OS) by PIK3CA Mutation Status Secondary · Study start date to study end date, or death, whichever comes first, up to 24 months

This has the same outcome measure description as the OS analysis.

GroupValue95% CI
PIK3CA Mutant929 – NA
PIK3CA Wild Type3620 – 85

Adverse events — posted to ClinicalTrials.gov

Time frame: 45 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Oral Cabozantinib
Serious: 20/44 (45%)
Deaths: 5/44

Serious adverse events (28 terms)

ReactionSystemOral Cabozantinib
Pleural EffusionRespiratory, thoracic and mediastinal disorders
Disease ProgressionGeneral disorders
dyspneaRespiratory, thoracic and mediastinal disorders
GI bleedGastrointestinal disorders
Lung infectionRespiratory, thoracic and mediastinal disorders
Cavitating Pulmonary NodulesRespiratory, thoracic and mediastinal disorders
Abdominal PainGastrointestinal disorders
Acute Cerebrovascular AccidentGeneral disorders
Acute PancreatitisGastrointestinal disorders
Acute Renal FailureRenal and urinary disorders
Back PainGeneral disorders
Bowel PerforationGastrointestinal disorders
ConstipationGastrointestinal disorders
DehydrationGeneral disorders
difficulty speakingGeneral disorders
Disseminated Intravascular CoagulationBlood and lymphatic system disorders
Duodenal fistulaGastrointestinal disorders
Failure to ThriveGeneral disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
nauseaGastrointestinal disorders
Bowel ObstructionGastrointestinal disorders
PneumoniaRespiratory, thoracic and mediastinal disorders
Progressed Malignant NeoplasmGeneral disorders
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders
Severe Complicated Bilateral PyelonephritisRenal and urinary disorders
Other adverse events (124 terms — click to expand)

ReactionSystemOral Cabozantinib
FatigueGeneral disorders
DiarrheaGastrointestinal disorders
NauseaGeneral disorders
PainGeneral disorders
Abdominal PainGastrointestinal disorders
AnorexiaGeneral disorders
HypertensionBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
palmar-plantar erythrodysesthesiaSkin and subcutaneous tissue disorders
Weight lossMetabolism and nutrition disorders
ProteinuriaRenal and urinary disorders
vomitingGastrointestinal disorders
HypothyroidismEndocrine disorders
CrampingMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedBlood and lymphatic system disorders
EdemaBlood and lymphatic system disorders
RefluxGastrointestinal disorders
HypokalemiaBlood and lymphatic system disorders
thrombocytopeniaBlood and lymphatic system disorders
feverGeneral disorders
Alkaline phosphatase increasedBlood and lymphatic system disorders
alanine aminotransferase increaseBlood and lymphatic system disorders
AnemiaBlood and lymphatic system disorders
NeuropathyNervous system disorders
DizzinessGeneral disorders
DysgeusiaGeneral disorders
CoughGeneral disorders
HematuriaRenal and urinary disorders
RashSkin and subcutaneous tissue disorders
sore throatGeneral disorders
AcheGeneral disorders
Bilirubin IncreasedBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
PruritusSkin and subcutaneous tissue disorders
MucositisSkin and subcutaneous tissue disorders
FlatulenceGastrointestinal disorders
HyperamylasemiaBlood and lymphatic system disorders
DyspneaRespiratory, thoracic and mediastinal disorders
Elevated CreatinineBlood and lymphatic system disorders
hoarseGeneral disorders

Most-reported serious reactions: Pleural Effusion, Disease Progression, dyspnea, GI bleed, Lung infection, Cavitating Pulmonary Nodules, Abdominal Pain, Acute Cerebrovascular Accident.

Data from ClinicalTrials.gov NCT03542877 adverse events section.

Sponsor's own description

This study seeks to use Cabozantinib to treat those with Metastatic Colorectal Cancer who have not previously responded to treatment.

Publications & conference data

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

  1. Comprehensive review of targeted therapy for colorectal cancer.
    Xie YH, Chen YX, Fang JY. · · 2020 · cited 1162× · PMID 32296018 · DOI 10.1038/s41392-020-0116-z
  2. Targeted Therapy for Cancers: From Ongoing Clinical Trials to FDA-Approved Drugs.
    Choi HY, Chang JE. · · 2023 · cited 77× · PMID 37686423 · DOI 10.3390/ijms241713618
  3. Molecular mechanisms targeting drug-resistance and metastasis in colorectal cancer: Updates and beyond.
    Al Bitar S, El-Sabban M, Doughan S, Abou-Kheir W. · · 2023 · cited 53× · PMID 36998426 · DOI 10.3748/wjg.v29.i9.1395
  4. BDNF and its signaling in cancer.
    Malekan M, Nezamabadi SS, Samami E, Mohebalizadeh M, et al · · 2023 · cited 48× · PMID 36173463 · DOI 10.1007/s00432-022-04365-8
  5. The Relevance of Transcription Factors in Gastric and Colorectal Cancer Stem Cells Identification and Eradication.
    Pádua D, Figueira P, Ribeiro I, Almeida R, et al · · 2020 · cited 34× · PMID 32626705 · DOI 10.3389/fcell.2020.00442
  6. Deciphering treatment resistance in metastatic colorectal cancer: roles of drug transports, EGFR mutations, and HGF/c-MET signaling.
    Albadari N, Xie Y, Li W. · · 2023 · cited 16× · PMID 38269272 · DOI 10.3389/fphar.2023.1340401
  7. A Phase II Study Investigating Cabozantinib in Patients with Refractory Metastatic Colorectal Cancer (AGICC 17CRC01).
    Scott AJ, Basu Mallick A, Dotan E, Cohen SJ, et al · · 2022 · cited 14× · PMID 36969746 · DOI 10.1158/2767-9764.crc-22-0169
  8. HGF/c-Met Axis: The Advanced Development in Digestive System Cancer.
    Shao Z, Pan H, Tu S, Zhang J, et al · · 2020 · cited 14× · PMID 33195182 · DOI 10.3389/fcell.2020.00801

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Other recruiting trials for Colorectal Cancer

Currently open trials in the same condition.

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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/NCT03542877.

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