Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer
- Conditions
- Metastatic Colorectal Adenocarcinoma
- Interventions
- Registration Number
- NCT03043313
- Lead Sponsor
- Seagen Inc.
- Brief Summary
This trial studies how well the drug tucatinib works when given with trastuzumab and when given by itself. The participants in this trial have HER2-positive (HER2+) metastatic colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the body.
In the first part of this study, participants enrolled into Cohort A and received both tucatinib and trastuzumab. In the second part of this study, participants are randomly assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do not respond to therapy may have an option to receive tucatinib plus trastuzumab.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 117
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Tucatinib + Trastuzumab Trastuzumab Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. Cohort A: Tucatinib + Trastuzumab Tucatinib Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. Cohort B: Tucatinib + Trastuzumab Trastuzumab Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days. Cohort C: Tucatinib Monotherapy Tucatinib Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab. Cohort B: Tucatinib + Trastuzumab Tucatinib Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
- Primary Outcome Measures
Name Time Method Confirmed Objective Response Rate (cORR) Per RECIST v1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B Up to 46.6 months cORR was defined as the percentage of participants with confirmed CR or PR according to RECIST v1.1. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to less than (\<)1.0 centimeter (cm). PR was defined as at least a 30 percentage (%) decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameters.
- Secondary Outcome Measures
Name Time Method ORR by 12 Weeks of Treatment Per RECIST v1.1 According to BICR Assessment Up to 3 months ORR per BICR by 12 Weeks was defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever came earlier. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than \<1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the baseline sum of diameter.
Duration of Response (DOR) Per RECIST v1.1 According to BICR Assessment Up to 64.1 months DOR was defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST v1.1 or death from any cause, whichever occurred first. CR was defined as the disappearance of all target lesions and each target lymph node must have reduction in short axis to more than \<1.0 cm. PR was defined as at least a 30% decrease in post-baseline sum of the diameters (PBSD) (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD. PD was defined as: at least one new malignant lesion, which also includes any lymph node that was normal at baseline (\<1.0 cm short axis) and increased to more than or equal to (\>=)1.0 cm short axis during follow-up or at least a 20% increase in PBSD taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.
Progression-Free Survival (PFS) Per RECIST v1.1 According to BICR Assessment for Pooled Cohorts A+B Up to 64.1 months PFS was defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST v1.1) or death from any cause, whichever occurred first. PD was defined as: at least one new malignant lesion, which also included any lymph node that was normal at baseline (\<1.0 cm short axis) and increased to \>=1.0 cm short axis during follow-up or at least a 20% increase in post-baseline sum of the diameters (PBSD) taking as reference the minimum sum of the diameters (MSD). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.
Overall Survival (OS) in Pooled Cohorts A+B Up to 71.8 months OS was defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.
Number of Participants With Adverse Events (AEs): Interim Analysis Up to 49.3 months AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab). Serious AE (SAE): An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE.
Number of Participants With AEs: Final Analysis Up to 65.1 months AE: Any untoward medical occurrence in a participant or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs): Events that were new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab). SAE: An event that at any dose led to death; life-threatening; required inpatient hospitalization/prolongation of existing hospitalization; persistent/significant disability/incapacity; congenital anomaly/birth defect/ important medical event. Treatment related AEs, SAEs, deaths also included. Relatedness was judged by investigator According to NCI CTCAE version 4.03: Grade(G) 3=severe AE, G4=life-threatening, urgent intervention indicated, G5=death related to AE.
Number of Participants With AEs Resulting in Dose Modification: Interim Analysis Up to 49.3 months Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.
Number of Participants With AEs Resulting in Dose Modification: Final Analysis Up to 65.1 months Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued. Drug interruption included infusion interrupted (full dose received within 24hrs).
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Interim Analysis Up to 49.3 months The following hematology laboratory parameters were assessed: Hemoglobin decreased; leukocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology): Final Analysis Up to 65.1 months The following hematology laboratory parameters were assessed: Hemoglobin decreased; hemoglobin increased; leukocytes decreased; lymphocytes decreased; neutrophils decreased and Platelets decreased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v4.03 was used for the lab parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Interim Analysis Up to 49.3 months The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased. Treatment emergent laboratory abnormalities were defined as abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 was used for creatinine increased. NCI CTCAE v4.03 was used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry): Final Analysis Up to 65.1 months The following chemistry laboratory parameters were assessed: Potassium increased; potassium decreased; aspartate aminotransferase increased; creatinine increased; alkaline phosphatase increased; total bilirubin increased; albumin decreased; calcium corrected for albumin decreased; calcium corrected for albumin increased; glomerular filtration rate (GFR), estimated decreased; glucose decreased; glucose increased; sodium decreased; sodium increased; calcium and ionized increased. Treatment emergent laboratory abnormalities: Abnormalities that were new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 used for creatinine increased. NCI CTCAE v4.03 used for the other laboratory parameters. Grade 1: mild; Grade 2: moderate; Grade 3: severe or clinically significant; Grade 4: life-threatening.
Number of Participants With Clinically Significant Vital Signs: Final Analysis Up to 65.1 months Vital signs included temperature, oxygen saturation, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate and weight. Vital signs were considered clinically significant: temperature: \>= 38 degree Celsius (C); oxygen saturation less than (\<)88%; SBP \>=120 millimeters of mercury (mmHg) or DBP \>=80 mmHg; SBP \>=140 mmHg or DBP \>=90 mmHg; SBP \>=160 mmHg or DBP \>=100 mmHg and heart rate \>100 beats per minute (bpm) and maximum decrease from baseline in weight in kilograms (kg).
Trial Locations
- Locations (56)
Texas Oncology - Beaumont
🇺🇸Beaumont, Texas, United States
Lombardi Cancer Center / Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Other, Spain
Aurora Research Institute Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Other, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Other, Spain
Keck Medical Center / University of Southern California
🇺🇸Los Angeles, California, United States
Winship Cancer Institute / Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Case Western Reserve University / University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
Indiana University Simon Cancer Center
🇺🇸Indianapolis, Indiana, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Rocky Mountain Cancer Centers - Aurora
🇺🇸Aurora, Colorado, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Stanford University School of Medicine
🇺🇸Palo Alto, California, United States
Saint Joseph Heritage Medical Group
🇺🇸Santa Rosa, California, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Allegheny General Hospital
🇺🇸Pittsburgh, Pennsylvania, United States
Texas Oncology - Baylor Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Texas Oncology - McAllen
🇺🇸McAllen, Texas, United States
Texas Oncology - San Antonio Medical Center
🇺🇸San Antonio, Texas, United States
Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Providence Regional Medical Center Everett
🇺🇸Everett, Washington, United States
Huntsman Cancer Institute/University of Utah
🇺🇸Salt Lake City, Utah, United States
Hopital Saint-Antoine
🇫🇷Paris, Other, France
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Florida Cancer Specialists - South Region
🇺🇸Fort Myers, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Niguarda Ca' Granda Hospital
🇮🇹Milan, Other, Italy
Northwest Cancer Specialists, P.C.
🇺🇸Portland, Oregon, United States
Tennessee Oncology-Nashville/Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Florida Cancer Specialists - North Region
🇺🇸Saint Petersburg, Florida, United States
Hôpital Franco-Britannique - Fondation Cognacq-Jay
🇫🇷Levallois-Perret, Other, France
Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara
🇮🇹Pisa, Other, Italy
Cliniques Universitaires Saint Luc
🇧🇪Brussels, Other, Belgium
Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes
🇫🇷Lyon, Other, France
Instituto Europeo di Oncologia
🇮🇹Milan, Other, Italy
Hospitalier Jean Minjoz
🇫🇷Besancon, Other, France
Center Georges Francois Leclerc
🇫🇷Dijon, Other, France
Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
🇺🇸Los Angeles, California, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
UZ Leuven campus Gasthuisberg
🇧🇪Leuven, Other, Belgium
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Karmanos Cancer Institute / Wayne State University
🇺🇸Detroit, Michigan, United States
Banner MD Anderson Cancer Center
🇺🇸Gilbert, Arizona, United States
University of Iowa Hospitals and Clinics
🇺🇸Iowa City, Iowa, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Other, Belgium
Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
🇪🇸L'Hospitalet de Llobregat, Other, Spain