A Study of Tucatinib and Trastuzumab in People With Rectal Cancer

NCT05672524 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-185
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Adenocarcinoma of the Rectum; Rectal Adenocarcinoma; Locally Advanced Rectal Adenocarcinoma; HER2 Positive Rectal Adenocarcinoma; Rectal Cancer

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

Outcome Measures

Primary Outcomes (1)

• Clinical complete response of study participants

  The primary objective of this trial is to determine the clinical complete response rate after the completion of initial neoadjuvant tucatinib and trastuzumab followed by standard of care induction chemotherapy (assessed around week 21 ± 4 weeks) in subjects with HER2-positive, RAS wild-type locally advanced rectal adenocarcinoma

  21 +/- 4 weeks

Study Arms (1)

Participant with Rectal Adenocarcinoma

EXPERIMENTAL

Participants will have HER2-positive locally advanced rectal adenocarcinoma.

Drug: Trastuzumab; Drug: Tucatinib

Interventions

Trastuzumab DRUG

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).

Participant with Rectal Adenocarcinoma

Tucatinib DRUG

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).

Participant with Rectal Adenocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• HER2+ overexpression (3+ immunohistochemistry \[IHC\]) by an FDA-approved HER2 IHC test following the package insert's interpretational manual for gastric cancer
• 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
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Center at Suffolk - Commack (Limited Protocol Activities)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Rectal Neoplasms; Adenocarcinoma

Interventions

Trastuzumab; tucatinib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Andrea Cercek, MD

  Memorial Sloan Kettering Cancer

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Cercek, MD

CONTACT

646-888-4189; cerceka@mskcc.org

Rona Yaeger, MD

CONTACT

646-888-5109; yaegerr@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 3, 2023
• First Posted: January 5, 2023
• Study Start: December 30, 2022
• Primary Completion (Estimated): July 30, 2027
• Study Completion (Estimated): July 31, 2030
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)