Study on Tucatinib and Trastuzumab for People with Rectal Cancer

Inclusion Criteria

• Be willing and able to provide written consent to participate in the study.
• Be 18 years or older.
• Have a performance status score of 0 or 1, indicating full activity or some restriction in strenuous activities.
• Have a confirmed diagnosis of rectal adenocarcinoma.
• The cancer must be located within 15 cm from the anal verge and staged as cT3/cT4 N0 or cT(any) cN1/2, with no distant metastases.
• Have measurable or evaluable disease as per study protocol.
• Have HER2-positive rectal adenocarcinoma confirmed by specific lab tests.
• Have a tumor that shows intact mismatch repair enzymes or microsatellite stability.
• Have a tumor that is RAS wild-type based on specific genetic testing.
• Have a heart function with an ejection fraction of 50% or higher.
• Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception during the study and for 150 days after the last dose.
• Demonstrate adequate organ function based on specific blood tests, including:
  • Neutrophil count of at least 1,500/mm3
  • Platelet count of at least 100,000/mcL
  • Hemoglobin level above 9 g/dL
  • Creatinine clearance of 60 mL/min or better
  • Liver function tests within specified limits
  • Blood clotting times within specified limits for those not on blood thinners

Exclusion Criteria

• Have recurrent rectal cancer.
• Have had prior radiation, chemotherapy, or surgery for rectal cancer.
• Have a tumor causing bowel obstruction, unless a temporary ostomy is in place.
• Have had another invasive cancer within the last 5 years, except for certain skin or cervical cancers.
• Have an active infection requiring treatment.
• Be receiving other cancer treatments or experimental therapies.
• Have a known history of HIV or active hepatitis B or C.
• Have chronic liver disease.
• Be pregnant or breastfeeding, or planning to conceive during the study and for 150 days after.
• Have medical or psychiatric conditions that would make participation unsafe.
• Have received a live vaccine within 30 days before starting the study.
• Have had major surgery or significant injury within 28 days before enrollment.
• Be unable to swallow pills or have gastrointestinal issues affecting medication absorption.
• Be using certain medications that affect drug metabolism and have not been cleared from the body before starting the study.