Trial Title:
A Study of Tucatinib and Trastuzumab in People With Rectal Cancer
NCT ID:
NCT05672524
Condition:
Adenocarcinoma of the Rectum
Locally Advanced Rectal Adenocarcinoma
Rectal Adenocarcinoma
HER2 Positive Rectal Adenocarcinoma
Rectal Cancer
Conditions: Official terms:
Adenocarcinoma
Rectal Neoplasms
Trastuzumab
Tucatinib
Conditions: Keywords:
HER2 positive rectal adenocarcinoma
Adenocarcinoma
Adenocarcinoma of the Rectum
Locally Advanced Rectal Adenocarcinoma
Rectal Adenocarcinoma
Rectal Cancer
Tucatinib
Trastuzumab
Memorial Sloan Kettering Cancer Center
22-185
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Trastuzumab
Description:
Patients will then be given tucatinib (300 mg BID orally) and trastuzumab (8 mg/kg on day
1, then 6 mg/kg starting cycle 2 and every three weeks) therapy for an initial 6 week
lead-in period. All patients, regardless of findings on rectal MRI will then transition
to standard of care induction chemotherapy with continuation of the trastuzumab and
tucatinib for a total of five additional cycles (15 extra weeks).
Arm group label:
Participant with Rectal Adenocarcinoma
Intervention type:
Drug
Intervention name:
Tucatinib
Description:
Patients will then be given tucatinib (300 mg BID orally) and trastuzumab (8 mg/kg on day
1, then 6 mg/kg starting cycle 2 and every three weeks) therapy for an initial 6 week
lead-in period. All patients, regardless of findings on rectal MRI will then transition
to standard of care induction chemotherapy with continuation of the trastuzumab and
tucatinib for a total of five additional cycles (15 extra weeks).
Arm group label:
Participant with Rectal Adenocarcinoma
Summary:
The study researchers believe that a combination of the drugs trastuzumab and tucatinib,
given with standard chemotherapy (capecitabine and oxaliplatin/FOLFOX), may help
participants with rectal cancer.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Willing and able to provide written informed consent for the trial.
- Be ≥18 years of age on the date of signing informed consent.
- ECOG performance status of 0 or 1.
- Histologically confirmed rectal adenocarcinoma.
- Adenocarcinoma with distal margin of 15 cm or less from the anal verge on endoscopy,
staged with endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI) as
cT3/cT4 N0 or cT(any) cN1/2,
- No evidence of distant metastases
- Radiologically measurable or clinically evaluable disease per Protocol Section 13.0.
- Have confirmed HER2-positive rectal adenocarcinoma, as defined by having tumor
tissue tested at a Clinical Laboratory Improvement Amendments (CLIA)-certified
laboratory, meeting at least one of the following criteria:
1. HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved HER2
IHC test following the package insert's interpretational manual for gastric
cancer
2. HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved HER2 in
situ hybridization assay (FISH or chromogenic in situ hybridization [CISH])
following the package insert's interpretational manual for gastric cancer
3. HER2 (ERBB2) amplification by CLIA-certified Next Generation Sequencing (NGS)
sequencing assay.
- Tumor specimen that demonstrates intact mismatch repair enzymes by
immunohistochemistry or microsatellite stability as demonstrated by NGS or PCR.
- Tumor specimen that indicates RAS wild-type based on expanded RAS testing including
KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117
and 146)
- Left ventricular ejection fraction >=50 assessed by echocardiography
- Negative pregnancy test done within 14 days prior to beginning treatment, for women
of childbearing potential only. Subjects of childbearing potential must be willing
to use an adequate method of contraception. Appropriate methods of birth control
include abstinence, oral contraceptives, implantable hormonal contraceptives, or
double barrier method (diaphragm plus condom). Contraception is required for the
course of the study starting with the first dose of study medication through 150
days after the last dose of study medication. Note: Abstinence is acceptable if this
is the usual lifestyle and preferred contraception for the subject.
Nonchildbearing potential is defined as follows (by other than medical reasons):
- ≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a hysterectomy
and oophorectomy must have a follicle stimulating hormone value in the
postmenopausal range upon screening evaluation
- Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation. Documented
hysterectomy or oophorectomy must be confirmed with medical records of the actual
procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with
medical records of the actual procedure, otherwise the patient must be willing to
use 2 adequate barrier methods throughout the study.
- Demonstrate adequate organ function as defined in the Table 6-1 below within 14 days
of Cycle 1 Day 1, all screening labs should be performed within 14 days of treatment
initiation.
- Absolute neutrophil count (ANC): ≥1,500 /mm3
- Platelets: ≥100,000 / mcL
- Hemoglobin: >9 g/dL or ≥5.6 mmol/L
- Serum creatinine OR Measured or calculated creatinine clearance (Creatinine
clearance should be calculated per institutional standard.) (GFR can also be
used in place of creatinine or CrCl): ≤1.5 × upper limit of normal (ULN) OR ≥60
mL/min for subject with creatinine levels > 1.5 × institutional ULN
- Serum total bilirubin: Total bilirubin ≤ 1.5 × upper limit of normal (ULN),
except for subjects with known Gilbert's disease who may enroll if the
conjugated bilirubin is ≥1.5 x ULN
- AST (SGOT) and ALT (SGPT): ≤ 2.5 × ULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial
Thromboplastin Time (aPTT): For patients not taking warfarin: INR <1.5 or PT
<1.5 x ULN; and either PTT or aPTT <1.5 x ULN. Patients on warfarin may be
included on a stable dose with a therapeutic INR <3.5
Exclusion Criteria:
- Recurrent rectal cancer.
- Prior pelvic radiation therapy, chemotherapy, or surgery for rectal cancer.
- Tumor is causing symptomatic bowel obstruction (patients who have a temporary
diverting ostomy are eligible).
- Other invasive malignancy ≤ 5 years prior to registration. Exceptions are
non-melanoma skin cancer that has undergone potentially curative therapy and in situ
cervical carcinoma.
- Active infection requiring systemic therapy.
- Other Anticancer or Experimental Therapy. No other experimental therapies (including
chemotherapy, radiation, hormonal treatment, antibody therapy, immunotherapy, gene
therapy, vaccine therapy, angiogenesis inhibitors, matrix metalloprotease
inhibitors, thalidomide, anti-VEGF/Flk-1 monoclonal antibody or other experimental
drugs) of any kind are permitted while the patient is receiving study treatment.
- Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
- Known active Hepatitis B (e.g., HbsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
- Any known chronic (non-transient) liver disease in the patient's past medical
history such as (but not limited to) cirrhosis, NASH (non-alcoholic steatohepatitis)
or NAFLD.
- Women who are pregnant or breastfeeding, or men expecting to conceive or father
children within the projected duration of the trial, starting with the pre-screening
visit through 150 days after the last dose of study medication.
- Concurrent medical or psychiatric condition or disease which, in the investigator's
judgement, would make them inappropriate candidates for entry into the study.
Examples include, but are not limited to, uncontrolled ventricular arrhythmia,
recent (within 90 days) myocardial infarction, chronic obstructive pulmonary
disease, uncontrolled major seizure disorder, unstable spinal cord compression,
superior vena cava syndrome, or any psychiatric disorder that prohibits obtaining
informed consent.
- Received a live vaccine within 30 days of planned start of study medication.
- Major surgical procedure, open biopsy, or significant traumatic injury within 28
days prior to enrollment.
- Inability to swallow pills or any significant gastrointestinal disease which would
preclude the adequate oral absorption of medications
- Use of a strong cytochrome P450 (CYP)2C8 inhibitor that is not adequately cleared
(five half-lives of elapsed time) before study initiation. In addition, use of a
strong CYP3A4 or CYP2C8 inducer that is taken within 5 days prior to the first dose
of study will also be an exclusion criteria.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Address:
City:
Basking Ridge
Zip:
07920
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Cercek, MD
Phone:
646-888-4189
Investigator:
Last name:
Andrea Cercek, MD
Email:
Principal Investigator
Facility:
Name:
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Address:
City:
Middletown
Zip:
07748
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Cercek, MD
Phone:
646-888-4189
Facility:
Name:
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Address:
City:
Montvale
Zip:
07645
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Cercek, MD
Phone:
646-888-4189
Facility:
Name:
Memorial Sloan Kettering Cancer Center at Suffolk - Commack (Limited Protocol Activities)
Address:
City:
Commack
Zip:
11725
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Cercek, MD
Phone:
646-888-4189
Facility:
Name:
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Address:
City:
Harrison
Zip:
10604
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Cercek, MD
Phone:
646-888-4189
Facility:
Name:
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrew Cercek, MD
Phone:
646-888-4189
Facility:
Name:
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Address:
City:
Uniondale
Zip:
11553
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andrea Cercek, MD
Phone:
646-888-4189
Start date:
December 30, 2022
Completion date:
December 30, 2025
Lead sponsor:
Agency:
Memorial Sloan Kettering Cancer Center
Agency class:
Other
Source:
Memorial Sloan Kettering Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05672524
http://www.mskcc.org
