An Open-label Randomized Phase 3 Study of Tucatinib in Combination with Trastuzumab and mFOLFOX6 versus mFOLFOX6 given with or without either Cetuximab or Bevacizumabas First-line Treatment for Subjects with HER2+Metastatic Colorectal Cancer
- Conditions
- Gastrointestinal disorders, Colorectal CancerHER2+ mCRCHER2+ metastatic colorectal cancer
- Registration Number
- NL-OMON56153
- Lead Sponsor
- Seagen, Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 16
Subjects must meet the following criteria to be eligible for the study:
1. Have histologically and/or cytologically documented adenocarcinoma of the
colon or rectum, which locally advanced or metastatic
2. Subjects must be willing and able to provide the most recently available
formalin-fixed paraffin-embedded tumor tissue blocks (or freshly sectioned
slides, see laboratory manual for details), obtained prior to treatment
initiation, to a sponsor-designated central laboratory for biomarker analysis.
If archival tissue is not available, then a newly- obtained baseline biopsy of
an accessible tumor lesion is required within 35 days prior to the Cycle 1 Day
1 timeframe. Biopsy must provide adequate tissue for analysis; the following
biopsy types are acceptable: resection, excision, punch (skin lesions only) and
core needle biopsies.
3. Have HER2+ disease as determined by tissue-based investigational HER2 IHC
and ISH assays performed at a sponsor-defined central laboratory. HER2
amplification will be determined using ASCO/CAP guidelines for gastric and
gastroesophageal cancer with IHC 3+ or IHC 2+/ISH+ result.
4. Have RAS WT disease as determined by local or central testing (if local
testing is unavailable or is not preferred). For central RAS analysis, tissue
sample must be analysed within 1 year of biopsy.
5. Age >=18 years at time of consent and >= the age of majority per regional
requirements
6. Have radiographically measurable disease per RECIST v1.1 according to INV
assessment, with at least one
site of disease that is measurable and that has not been previously irradiated;
or, if the subject has had previous radiation to the target lesion(s), there
must be evidence of progression since the radiation
7. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of
0 or 1
8. Life expectancy of >=3 months, in the opinion of the investigator
9. Have adequate hematological, hepatic, renal, coagulation, and cardiac
function, as defined below, obtained <=7 days prior to enrollment (Cycle 1 Day
1):
a. Absolute neutrophil count (ANC) >=1.5 × 103/µL
b. Platelet count >=100 × 103/µL
c. Hemoglobin >=9.0 g/dL
d. Total bilirubin <=1.5 × upper limit of normal (ULN). Subjects with known
history of Gilbert*s Syndrome may enroll if direct bilirubin is <=1.5 × ULN
e. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <=3 × ULN
(<=5 × ULN if liver
metastases are present)
f. Creatinine level <=1.5 × institutional ULN or estimated creatinine clearance
>=60 mL/min for subjects with
creatinine levels >1.5 × institutional ULN
g. International normalized ratio (INR) and activated partial thromboplastin
time (aPTT) <=1.5 × ULN unless on medication known to alter INR and/or aPTT
h. Left ventricular ejection fraction (LVEF) >=50% as assessed by echocardiogram
(ECHO) or multiple-gated acquisition (MUGA) scan documented <=28 days prior to
study treatment
10. For subjects of childbearing potential, the following stipulations apply:
a. Must have a negative serum pregnancy test (minimum sensitivity of 25 mIU/mL
or equivalent units of beta human chorionic gonadotropin [β-hCG]) result within
7 days prior to the first dose of study treatment. A subject with a false
positive result and documented verification that the subject i
Subjects will be excluded from the study for any of the following reasons:
1. Have previously received any systemic anticancer therapy for CRC in the
metastatic setting or have participated in any interventional clinical trial
for CRC in the metastatic setting.
Note: that subjects may have received a maximum of 2 doses of mFOLFOX6 in the
locally advanced/unresectable or metastatic setting prior to randomization.
Note: Subjects may have received prior chemotherapy for CRC in the adjuvant
setting provided that it was completed >6 months prior to enrollment.
2. Have previously received radiation therapy within 14 days prior to
enrollment (or within 7 days in the setting of SRS). Subjects who have received
prior radiation therapy must have recovered to baseline from any treatment-
related adverse events (AEs). Subjects who have received palliative
radiotherapy for symptomatic metastases
may enter the study without a washout period provided that the subject has
recovered from any treatment-related AEs.
3. Have previously been treated with anti-HER2 therapy
4. Have any toxicity related to prior cancer therapies that has not resolved to
<= Grade 1, with the following exceptions:
• Neuropathy, which must have resolved to <= Grade 2
• Alopecia
• Congestive heart failure (CHF), which must have been <= Grade 1 in severity at
the time of occurrence, and must have resolved completely
• Anemia, hemoglobin must have resolved to a level of >=9.0 g/dL
5. Have clinically significant cardiopulmonary disease such as:
• Ventricular arrhythmia requiring therapy
• Symptomatic hypertension or uncontrolled asymptomatic hypertension, as
determined by the investigator
• Any history of symptomatic CHF (Grade 2 or above), symptomatic left
ventricular systolic dysfunction or symptomatic decrease in ejection fraction
• Severe dyspnea at rest (Grade 3 or above) due to complications of advanced
malignancy or hypoxia requiring supplementary oxygen therapy
• Presence of >= Grade 2 corrected QT interval (QTc) prolongation (>480 ms) on
screening electrocardiogram
(ECG)
• Interstitial lung disease or pneumonitis
• Have a history of transient ischemic attack, cerebrovascular accident,
myocardial infarction, unstable angina, cardiac or other vascular stenting,
angioplasty, or cardiac surgery within 6 months prior to enrollment (Cycle 1
Day 1)
6. Have a history of a significant bleeding events within 6 months of
enrollment, unless the source of bleeding has been definitively treated
7. Have a history of gastrointestinal (GI) perforation within 12 months of
enrollment
8. Have ongoing >= Grade 2 diarrhea of any etiology
9. Major surgical procedure or significant traumatic injury <=28 days prior to
enrollment (<=56 days for hepatectomy, open thoracotomy, or major neurosurgery)
or anticipation of need for major surgical procedure during the course
of the study
10. Serious, non-healing wound, ulcer, or bone fracture
11. Positive for hepatitis B by surface antigen expression or presence of known
chronic liver disease
12. Have active hepatitis C infection (positive by PCR or on antiviral therapy
for hepatitis C within the last 6 months). Subjects who have been treated for
hepatitis C infection are permitted if they have documented
sustained virologic response of 12 week
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Objective:<br /><br>To compare progression-free survival (PFS) per Response Evaluation Criteria in<br /><br>Solid Tumors 1.1 (RECIST v1.1) according to blinded independent central review<br /><br>(BICR) assessment between treatment arms.</p><br>
- Secondary Outcome Measures
Name Time Method