Adenocarcinoma of the RectumPhase 2NCT05672524
A Study of Tucatinib and Trastuzumab in People With Rectal Cancer
A Phase 2 study testing Trastuzumab and Tucatinib in people with Adenocarcinoma of the Rectum and Locally Advanced Rectal Adenocarcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Rectum, Locally Advanced Rectal Adenocarcinoma, Rectal Adenocarcinoma
- What is being tested?
- Trastuzumab and Tucatinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 7 sitesUnited States
- Study dates
- 30 Dec 2022to 31 Jul 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
7 sites in 1 country. Contact the study team or a site near you to ask about taking part.
7 sites in 1 country
United States7 sites, 7 recruiting
- Recruiting
Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)
Basking Ridge, New Jersey, 07920
Andrea Cercek, MD, 646-888-4189
Andrea Cercek, MD
- Recruiting
Memorial Sloan Kettering Cancer Center at Suffolk - Commack (Limited Protocol Activities)
Commack, New York, 11725
Andrea Cercek, MD, 646-888-4189
- Recruiting
Memorial Sloan Kettering Westchester (Limited Protocol Activities)
Harrison, New York, 10604
Andrea Cercek, MD, 646-888-4189
- Recruiting
Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
Middletown, New Jersey, 07748
Andrea Cercek, MD, 646-888-4189
- Recruiting
Memorial Sloan Kettering Bergen (Limited Protocol Activities)
Montvale, New Jersey, 07645
Andrea Cercek, MD, 646-888-4189
- Recruiting
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
New York, New York, 10065
Andrew Cercek, MD, 646-888-4189
- Recruiting
Memorial Sloan Kettering Nassau (Limited Protocol Activities)
Uniondale, New York, 11553
Andrea Cercek, MD, 646-888-4189
About this study
Official title: A Phase II Study of Induction Tucatinib and Trastuzumab With Total Neoadjuvant Therapy for Locally Advanced HER2-amplified Rectal Adenocarcinoma
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, Locally Advanced Rectal Adenocarcinoma, Rectal Adenocarcinoma, HER2 Positive Rectal Adenocarcinoma, Rectal Cancer
- Being tested
- Trastuzumab, Tucatinib
- 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
- Medical subject headings
- Rectal Neoplasms, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
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).
TucatinibDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| Participant with Rectal Adenocarcinoma | Experimental | Participants will have HER2-positive locally advanced rectal adenocarcinoma. Receives: Drug: Trastuzumab; Drug: Tucatinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 21 +/- 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2023
- Study start30 Dec 2022
- Primary completion30 Jul 2027 (estimated)
- Study completion31 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adenocarcinoma of the RectumStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrea Cercek, MD, Principal investigator, Memorial Sloan Kettering Cancer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05672524
- Sponsor's protocol ID
- 22-185
- Status last verified
- May 2026
- First submitted
- 3 Jan 2023
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Induction Tucatinib and Trastuzumab With Total Neoadjuvant Therapy for Locally Advanced HER2-amplified Rectal Adenocarcinoma
- ClinicalTrials.gov ID
- NCT05672524
- Acronym / sponsor ID
- 22-185
- Conditions
- Adenocarcinoma of the Rectum, Locally Advanced Rectal Adenocarcinoma, 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- 30 Dec 2022 (actual)
- Primary completion
- 30 Jul 2027 (estimated)
- Study completion
- 31 Jul 2030 (estimated)
- First posted
- 5 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participant with Rectal Adenocarcinoma | Experimental | Drug: Trastuzumab, Drug: TucatinibParticipants will have HER2-positive locally advanced rectal adenocarcinoma. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- 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,
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TrastuzumabPatients 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). | Drug | Participant with Rectal Adenocarcinoma |
| TucatinibPatients 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). | Drug | Participant with Rectal Adenocarcinoma |
Primary outcome
Clinical complete response of study participants
Time frame: 21 +/- 4 weeks
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Andrea Cercek, MD principal investigator
Memorial Sloan Kettering Cancer
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Trastuzumab and Tucatinib in people with Adenocarcinoma of the Rectum and Locally Advanced Rectal Adenocarcinoma, run by Memorial Sloan Kettering Cancer Center at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea Cercek, MD (646-888-4189, cerceka@mskcc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical complete response of study participants (time frame: 21 +/- 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.