Tucatinib (ONT-380) and Trastuzumab in Treating Patients With HER2+ Metastatic Colorectal Cancer
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|ClinicalTrials.gov Identifier: NCT03043313|
Recruitment Status : Recruiting
First Posted : February 6, 2017
Last Update Posted : October 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|ERBB2 Gene Amplification HER2/Neu Positive KRAS wt Allele Metastatic Colon Adenocarcinoma Metastatic Colorectal Adenocarcinoma Metastatic Rectal Adenocarcinoma NRAS wt Allele Recurrent Colorectal Carcinoma Stage III Colon Cancer AJCC v7 Stage III Colorectal Cancer AJCC v7 Stage III Rectal Cancer AJCC v7 Stage IIIA Colon Cancer AJCC v7 Stage IIIA Colorectal Cancer AJCC v7 Stage IIIA Rectal Cancer AJCC v7 Stage IIIB Colon Cancer AJCC v7 Stage IIIB Colorectal Cancer AJCC v7 Stage IIIB Rectal Cancer AJCC v7 Stage IIIC Colon Cancer AJCC v7 Stage IIIC Colorectal Cancer AJCC v7 Stage IIIC Rectal Cancer AJCC v7 Stage IV Colon Cancer AJCC v7 Stage IV Colorectal Cancer AJCC v7 Stage IV Rectal Cancer AJCC v7 Stage IVA Colon Cancer AJCC v7 Stage IVA Colorectal Cancer AJCC v7 Stage IVA Rectal Cancer AJCC v7 Stage IVB Colon Cancer AJCC v7 Stage IVB Colorectal Cancer AJCC v7 Stage IVB Rectal Cancer AJCC v7 Unresectable Colon Adenocarcinoma Unresectable Rectal Adenocarcinoma||Biological: Trastuzumab Drug: Tucatinib||Phase 2|
I. To assess the objective response rate (ORR) of tucatinib in combination with trastuzumab in patients with HER2 positive (+) metastatic CRC.
I. To assess the clinical benefit rate (CBR) (stable disease [SD] for >= 6 months, or best response of complete response [CR] or partial response [PR]) of tucatinib in combination with trastuzumab.
II. To assess the progression free survival (PFS) of tucatinib in combination with trastuzumab.
III. To assess the duration of response of tucatinib in combination with trastuzumab.
IV. To assess the overall survival (OS) of tucatinib in combination with trastuzumab.
V. To assess the safety and tolerability of tucatinib in combination with trastuzumab.
CORRELATIVE RESEARCH OBJECTIVES:
I. To determine whether the combination of tucatinib and trastuzumab eliminates HER2 amplified circulating tumor deoxyribonucleic acid (DNA) (ctDNA) from peripheral blood.
II. To explore any correlation between tissue and blood based biomarkers and clinical outcomes.
Patients receive tucatinib orally (PO) twice daily (BID) on days 1-21 and trastuzumab intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and then every 12 weeks.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||40 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer|
|Actual Study Start Date :||June 23, 2017|
|Estimated Primary Completion Date :||June 30, 2020|
|Estimated Study Completion Date :||June 30, 2022|
Experimental: Treatment (tucatinib, trastuzumab)
Patients receive tucatinib PO BID on days 1-21 and trastuzumab IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
- Objective response rate [ Time Frame: Up to 4 months ]Defined as a complete response (CR) or partial response (PR) measured by Response Evaluation Criteria in Solid Tumors 1.1. Objective response rate over at most two post-baseline scans (approximately 4 months) with the exception that the 4-week confirmatory scans will not be required. The proportion of unconfirmed tumor responses (successes) will be estimated by the number of successes divided by the total number of evaluable patients. The null hypothesis that the proportion of evaluable patients with CR or PR (p) equals 0.2 (H0: p=0.2) will be tested against the alternative that this proportion equals 0.4 (HA: p=0.4). Confidence intervals for the true success proportion will be calculated using the normal approximation.
- Clinical best response [ Time Frame: Up to 2 years ]Defined as the proportion of patients who experience stable disease for >= 6 months, or a best response of complete or Partial response. Will be estimated by the 95% confidence interval estimates.
- Overall survival [ Time Frame: From registration to death due to any cause, assessed up to 2 years ]The distribution of overall survival will be estimated using the method of Kaplan-Meier.
- Progression free survival [ Time Frame: From registration to the earliest date of documented disease progression, assessed up to 2 years ]The distribution of time to progression will be estimated using the method of Kaplan-Meier.
- Duration of response [ Time Frame: Up to 2 years ]Defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status is first noted to be either a complete or partial response to the earliest date progression is documented. The duration of response will be assessed descriptively.
- Incidence of adverse events of grade 2 and above [ Time Frame: Up to 2 years ]Adverse events will be described by grade for grade 2 and above with and without attribution considered. All eligible patients that have initiated treatment will be considered evaluable for assessing adverse event rate(s). The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the adverse event(s) to the study treatment will be taken into consideration.
- Archived tumor tissue analysis [ Time Frame: Up to 2 years ]Analyses may include, but are not limited to, immunohistochemistry for HER2 expression, florescence in situ hybridization for HER2 amplification, and next generation sequencing.
- Circulating tumor deoxyribonucleic acid [ Time Frame: Up to 2 years ]These analyses will be descriptive.
- Blood biomarker analysis [ Time Frame: Up to 2 years ]Biomarker analyses will be considered exploratory. Analyses of interest will be correlated with progression free survival and tumor response using univariate and multivariate Cox models. P values will be reported but will be considered descriptive.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03043313
|Contact: Seattle Genetics Trial Information Supportemail@example.com|
|United States, Arizona|
|Mayo Clinic Hospital||Recruiting|
|Phoenix, Arizona, United States, 85054|
|Contact: Theresa Araque 480-342-4028 firstname.lastname@example.org|
|Principal Investigator: Tanios S. Bekaii-Saab|
|Mayo Clinic in Arizona||Recruiting|
|Scottsdale, Arizona, United States, 85259|
|Contact: Clinical Trials Referral Office 855-776-0015 email@example.com|
|Principal Investigator: Tanios S. Bekaii-Saab|
|United States, Georgia|
|Emory University Hospital/Winship Cancer Institute||Recruiting|
|Atlanta, Georgia, United States, 30322|
|Contact: Trafina Jadhav 404-778-5244 Trafina.Jadhav@emory.edu|
|Principal Investigator: Christina S. Wu|
|United States, Massachusetts|
|Dana-Farber Cancer Institute||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Larissa Masnyk 617-632-3773 Larissa_Masnyk@DFCI.harvard.edu|
|Principal Investigator: Kimmie Ng|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Contact: Clinical Trials Referral Office 855-776-0015|
|Principal Investigator: Axel Grothey|
|United States, New York|
|Roswell Park Cancer Institute||Recruiting|
|Buffalo, New York, United States, 14263|
|Contact: Karen A. Hicks 716-845-8947 firstname.lastname@example.org|
|Principal Investigator: Patrick M. Boland|
|Memorial Sloan Kettering Cancer Center||Recruiting|
|New York, New York, United States, 10065|
|Contact: Asha Krishnan 646-888-1377 email@example.com|
|Principal Investigator: Andrea Cercek|
|United States, North Carolina|
|Duke University Medical Center||Recruiting|
|Durham, North Carolina, United States, 27710|
|Contact: John H. Strickler 919-668-1861 firstname.lastname@example.org|
|Principal Investigator: John H. Strickler|
|United States, Wisconsin|
|Aurora Cancer Care-Milwaukee West||Recruiting|
|Wauwatosa, Wisconsin, United States, 53226|
|Contact: Karen Globke 414-302-2304 email@example.com|
|Principal Investigator: Federico Augusto H. Sanchez|
|Study Chair:||John H Strickler||Academic and Community Cancer Research United|
|Study Director:||Michael Stecher, MD||Seattle Genetics, Inc.|