Actively Recruiting
A Phase II Study of Tucatinib and Trastuzumab With Total Neoadjuvant Therapy for Locally Advanced HER2-Positive Rectal Adenocarcinoma
Led by Memorial Sloan Kettering Cancer Center · Updated on 2026-05-12
37
Participants Needed
7
Research Sites
156 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a combination of the drugs trastuzumab and tucatinib alongside standard chemotherapy to treat participants with HER2-positive locally advanced rectal adenocarcinoma. This phase II study aims to assess whether adding these targeted drugs to standard treatment can help improve outcomes for people with this type of rectal cancer. Participants will receive tucatinib orally twice daily and trastuzumab by infusion during an initial 6-week lead-in period. Following this, all patients will continue with standard induction chemotherapy while still taking tucatinib and trastuzumab for an additional 15 weeks. The treatment focuses on combining these therapies to manage the cancer before surgery. During the study, participants will be closely monitored through clinical evaluations including imaging to assess the cancer's response around 21 weeks after starting treatment. Researchers will measure the clinical complete response as the primary outcome. Safety and organ function will be regularly assessed, and participants will be followed for treatment adherence and overall health throughout the study period.
CONDITIONS
Brief Title
A Study of Tucatinib and Trastuzumab in People With Rectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Willing and able to provide written informed consent for the trial
- 18 years of age or older at the time of signing informed consent
- ECOG performance status of 0 or 1
- Histologically confirmed rectal adenocarcinoma
- Tumor located 15 cm or less from the anal verge, staged as cT3/cT4 N0 or cT(any) N1/2
- No evidence of distant metastases
- Radiologically measurable or clinically evaluable disease
- Confirmed HER2-positive status by approved tests (IHC 3+, IHC 2+ with amplification, or NGS assay)
- Tumor shows intact mismatch repair enzymes or microsatellite stability
- Tumor is RAS wild-type based on expanded RAS testing
- Left ventricular ejection fraction of 50% or higher
- Negative pregnancy test for women of childbearing potential within 14 days before treatment
- Willingness to use adequate contraception during and for 150 days after treatment
- Adequate organ function as defined by specific laboratory criteria within 14 days of treatment start
You will not qualify if you...
- Recurrent rectal cancer
- Prior pelvic radiation, chemotherapy, or surgery for rectal cancer
- Tumor causing symptomatic bowel obstruction (except patients with temporary diverting ostomy)
- Other invasive malignancy within 5 years, excluding certain skin and cervical cancers
- Active infection requiring systemic therapy
- Use of other anticancer or experimental therapies during study treatment
- Known HIV infection
- Active Hepatitis B or C infection
- Known chronic liver disease such as cirrhosis, NASH, or NAFLD
- Pregnant or breastfeeding women, or men planning to conceive during the study period
- Medical or psychiatric conditions that would make participation inappropriate
- Receipt of live vaccine within 30 days before starting treatment
- Major surgery, open biopsy, or significant injury within 28 days before enrollment
- Inability to swallow pills or gastrointestinal conditions preventing oral absorption
- Use of strong CYP2C8 inhibitors or CYP3A4/CYP2C8 inducers shortly before study start
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 6 weeks
Participants receive tucatinib orally twice daily and trastuzumab intravenously, starting with a loading dose followed by maintenance doses every three weeks for an initial 6 week lead-in period.
Visits every three weeks during treatment
Duration - 15 weeks
Participants continue tucatinib and trastuzumab alongside standard of care induction chemotherapy for five additional cycles, totaling approximately 15 weeks.
Visits every three weeks during treatment
Trial Site Locations
Total: 7 locations
1
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, United States, 07920
Actively Recruiting
2
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, United States, 07748
Actively Recruiting
3
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, United States, 07645
Actively Recruiting
4
Memorial Sloan Kettering Cancer Center at Suffolk - Commack (Limited Protocol Activities)
Commack, New York, United States, 11725
Actively Recruiting
5
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, United States, 10604
Actively Recruiting
6
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, United States, 10065
Actively Recruiting
7
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, United States, 11553
Actively Recruiting
Research Team
A
Andrea Cercek, MD
R
Rona Yaeger, MD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here