Metastatic Colorectal CancerPhase 2NCT03457896
Study of Neratinib +Trastuzumab or Neratinib + Cetuximab in Patients With KRAS/NRAS/BRAF/PIK3CA Wild-Type Metastatic Colorectal Cancer by HER2 Status
A Phase 2 study testing Trastuzumab, Cetuximab and Neratinib in people with Metastatic Colorectal Cancer, run by NSABP Foundation Inc at 48 sites in United States.
Trial summary
This is a phase II trial to examine the efficacy of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (all RAS/NRAS/BRAF/PIK3CA wild-type), metastatic colorectal cancer based on HER2 status (amplified, non-amplified [wild-type] or mutated). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Trastuzumab, Cetuximab and Neratinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 48 sitesUnited States
- Study dates
- 18 May 2018to 30 Sep 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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
- The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIK3CA (all RAS quadruple) wild-type by CLIA testing.
- The ECOG performance status must be 0, 1 or 2. Patients must have the ability to swallow and retain oral medication. There must be documentation by CT scan, or MRI, that the patient has evidence of measurable metastatic disease per RECIST 1.1 criteria.
- Patients must have an accessible metastatic lesion for pretreatment core biopsy procurement.
- Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard chemotherapy regimens. (This includes adjuvant therapy.)
- Specific patient eligibility for quadruple WT and HER2 status:
- Arm 1:
Show all 19Show fewer
- HER2 amplified confirmed by CLIA testing performed on blood samples, and prior treatment with cetuximab or panitumumab.
- HER2 mutation confirmed by CLIA testing of tumor, and with or without prior treatment with cetuximab or panitumumab.
- Arm 2:
- HER2 WT or HER2 amplified confirmed by CLIA testing of this tumor, and no prior therapy with cetuximab or panitumumab.
- Blood counts performed within 2 weeks prior to study entry must meet the following criteria:
- ANC must be greater than or equal to 1000/mm3. Platelet count must be greater than or equal to 75,000/mm3. Hemoglobin must be greater than or equal to 8 g/dL.
- Adequate hepatic function performed within 2 weeks prior to study entry must be met:
- Total bilirubin must be less than or equal to 1.5 x ULN (upper limit of normal) for the lab unless the patient has a bilirubin elevation greater than 1.5 x ULN to 3 x ULN due to Gilbert's disease or similar syndrome involving slow conjugation of bilirubin; and
- Alkaline phosphatase must be less than or equal to 3 x ULN for the lab with the following exception: for patients with documented liver metastases or bone involvement alkaline phosphatase must be less than or equal to 5 x ULN; and
- AST and ALT must be less than or equal to 3 x ULN for the lab with the following exception: for patients with documented liver metastases, AST and ALT must be less than or equal to 5 x ULN.
- Serum creatinine performed within 2 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab.
- Patients eligible for Arm 1 (neratinib + trastuzumab): Left ventricular ejection fraction must be greater than or equal to 50% or within normal range for the institution (whichever is lowest).
- Female patients and male patients with female partners of reproductive potential must agree to use an effective method of contraception during therapy and for at least 7 months after the last dose of study therapy.
Who cannot join
- Diagnosis of anal or small bowel carcinoma. Colorectal cancer histology other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
- Previous therapy with any HER2 targeting agents (such as trastuzumab, lapatinib, neratinib, etc.) for any malignancy.
- Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms.
- Active hepatitis B or hepatitis C with abnormal liver function tests. Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
- Persistent CTCAE v4.0 greater than or equal to grade 2 diarrhea regardless of etiology.
- CTCAE v4.0 grade 3 or 4 anorexia or nausea related to metastatic disease. CTCAE v4.0 greater than or equal to grade 2 vomiting related to metastatic disease.
Show all 11Show fewer
- Any of the following cardiac conditions: documented congestive heart failure; myocardial infarction within 6 months prior to study entry; unstable angina within 6 months prior to study entry; symptomatic arrhythmia.
- Serious or non-healing wound, skin ulcer, or bone fracture. History of bleeding diathesis. (Patients on stable anticoagulant therapy are eligible.) Symptomatic interstitial lung disease or definitive evidence of interstitial lung disease described on CT scan, MRI, or chest x-ray in asymptomatic patients; dyspnea at rest requiring current continuous oxygen therapy.
- Previous serious hypersensitivity reaction to monoclonal antibodies. (Determination of "serious" hypersensitivity reaction is at the investigator's discretion.) Other malignancies unless the patient is considered to be disease-free and has completed therapy for the malignancy greater than or equal to 12 months prior to study entry. Patients with the following cancers are eligible if diagnosed and treated within the past 12 months: carcinoma in situ of the cervix, colorectal carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
- Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude the patient from meeting the study requirements.
- Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be performed within 14 days prior to study entry according to institutional standards for women of childbearing potential.) Use of any investigational agent within 4 weeks prior to study entry. Note: Use of agents known to be strong cytochrome P450 (CYP) 3A4 inducers or inhibitors, and proton pump inhibitors (PPIs) should be avoided for the duration of study therapy.
Trial locations and contacts
48 sites in 1 country.
48 sites in 1 country
United States48 sites
Kaiser Permanente-Anaheim
Anaheim, California, 92806
Trinity Health Michigan
Ann Arbor, Michigan, 48106
Kaiser Permanente-Baldwin
Baldwin Park, California, 91706
Bronson Battle Creek
Battle Creek, Michigan, 49017
Kaiser Permanente-Bellflower
Bellflower, California, 90706
St. Joseph Mercy Brighton
Brighton, Michigan, 48114
Wellmont Medical Associates-Oncology and Hematology
Bristol, Virginia, 24201
St. Joseph Mercy Canton
Canton, Michigan, 48188
St. Joseph Mercy Chelsea
Chelsea, Michigan, 48118
Cancer Care Specialists of Central IL-Decatur
Decatur, Illinois, 62526
Decatur Memorial Hospital
Decatur, Illinois, 62526
Crosslands Cancer Center
Effingham, Illinois, 62401
Kaiser Permanente-Fontana
Fontana, California, 92335
UF Health Davis Cancer Pavilion and Shands Medical Plaza
Gainesville, Florida, 32608
University of Florida
Gainesville, Florida, 32610
Cancer Research Consortium of West Michigan
Grand Rapids, Michigan, 49503-2560
Spectrum Health Butterworth
Grand Rapids, Michigan, 49503
Kaiser Permanente-Harbor City
Harbor City, California, 90710
Kaiser Permanente-Irvine
Irvine, California, 92618
Wellmont Cancer Institute
Johnson City, Tennessee, 37601
Wellmont Cancer Institute
Kingston, Tennessee, 37660
St. Mary Mercy Hospital
Livonia, Michigan, 48154
Kaiser Permanente-Sunset
Los Angeles, California, 90027
Kaiser Permanente-West Los Angeles (Cadillac)
Los Angeles, California, 90034
Mercy Health Mercy Campus
Muskegon, Michigan, 49444
Southwest Virginia Regional Cancer Center
Norton, Virginia, 24273
Kaiser Permanente-Oakland
Oakland, California, 94611
Kaiser Permanente-Panorama City
Panorama City, California, 91402
Thomas Jefferson University Hospital-Sidney Kimmel Cancer Network
Philadelphia, Pennsylvania, 19107
Kaiser Permanente-Riverside
Riverside, California, 92505
Kaiser Permanente-Roseville
Roseville, California, 95661
Kaiser Permanente-Sacramento
Sacramento, California, 95814
St. Mary's of Michigan
Saginaw, Michigan, 48601
Lakeland Healthcare-Marie Yeager Cancer Center
Saint Joseph, Michigan, 49085
Minnesota Oncology-Fridley
Saint Louis Park, Minnesota, 55432
Kaiser Permanente-Medical Group
San Diego, California, 92108
Kaiser Permanente-Zion
San Diego, California, 92120
Kaiser Permanente-San Francisco
San Francisco, California, 94115
Kaiser Permanente-San Jose
San Jose, California, 95119
Kaiser Permanente-San Leandro
San Leandro, California, 94577
Kaiser Permanente-San Marcos
San Marcos, California, 92078
Kaiser Permanente Medical Center Santa Clara
Santa Clara, California, 95051
Kaiser Permanente-South San Francisco
South San Francisco, California, 94080
Cancer Care Specialists of Central IL-Swansea
Swansea, Illinois, 62226
Kaiser Permanente-Vallejo
Vallejo, California, 94589
Kaiser Permanente-Walnut Creek
Walnut Creek, California, 94596
Kaiser Permanente-Woodland Hills
Woodland Hills, California, 91367
Metro Health Hospital
Wyoming, Michigan, 49519
About this study
Official title: A Phase II Study Evaluating the Combination of Neratinib Plus Trastuzumab or Neratinib Plus Cetuximab in Patients With "Quadruple Wild-Type" (KRAS/NRAS/BRAF/PIK3CA Wild-Type) Metastatic Colorectal Cancer Based on HER2 Status: Amplified, Non-Amplified (Wild-Type) or Mutated
This is a phase II trial to examine the efficacy of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (all RAS/NRAS/BRAF/PIK3CA wild-type), metastatic colorectal cancer based on HER2 status (amplified, non-amplified [wild-type] or mutated). Patients must have confirmed quadruple wild-type (WT) genotype, via NSABP MPR-1 or from colonic biopsy or a metastatic biopsy taken prior to treatment, and known HER2 status.
Read the detailed description
The primary aim of this study is to determine the progression-free survival (PFS) in each of these HER2 populations. Secondary aims include overall response rate (ORR) and clinical benefit rate (CBR) defined as the objective tumor decrease and stable disease by RECIST 1.1 criteria; toxicity and safety profile. Exploratory analysis will be performed to assess for molecular predictors of response. The local site will make the primary determination of response and progression based on all radiographic images (e.g., MRI, CT, PET, bone scan, etc.) as well as other relevant reports documenting disease response or progression.
For patients identified as quadruple WT with prior cetuximab or panitumumab treatment, a pre-entry blood sample will be required from consenting patients to confirm HER2 amplification for study eligibility.
Patients with quadruple WT, HER2 amplified with prior anti-EGRF therapy and/or HER2 mutated colorectal cancer with/or without prior anti-EGRF therapy will receive concurrent therapy with trastuzumab 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly and neratinib 240 mg taken by mouth daily until disease progression, (Arm 1).
Patients with quadruple WT, HER2 WT or HER2 amplified with no prior anti-EGRF therapy will be assigned to receive concurrent therapy with cetuximab (400 mg/m2 IV loading dose followed by 250 mg/m2 IV weekly), and neratinib 240 mg taken by mouth daily until disease progression (Arm 2).
Approximately thirty-five (35) patients will be accrued to this study; 15 patients with HER2 amplified, 15 patients with HER2 WT, and approximately 5 patients with HER2 mutated colorectal cancer. Patients with HER2 WT or HER2 amplified mCRC who drop out of the study before the first scan (for whatever reason) will be replaced. Patients who drop out of the study after the first scan but before the second scan will be considered to have progressive disease.
Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Required blood and tissue samples will be collected at entry into the study. A tumor biopsy will be procured from an accessible site of metastasis before study therapy is initiated (after the patient has signed the consent form and has been screened for eligibility). Tissue will be sent to Champions Oncology Laboratory for engraftment into an NOD/SCID mouse to develop a patient-derived xenograft (PDX) model, and to NSABP Pathology Division for correlative science. Tissue samples from PDX models will be sent to Celcuity for functional HER2 signaling assay. Additional blood samples will be collected during the course of treatment.
Optional tumor and blood samples will be collected from consenting patients at the time of disease progression.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Trastuzumab, Cetuximab, Neratinib, Guardant360 Diagnostic Test
- Keywords
- NSABP, PUMA, Neratinib, Trastuzumab, Cetuximab, RAS, NRAS, BRAF, PIK3CA wild-type, Quadruple wild-type, HER2 status
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Patients with HER2 amplified tumors with prior anti-EGFR therapy and/or HER2 mutated colorectal cancer with/or without prior anti-EGFR therapy will receive 4 mg/kg IV loading dose; then 2 mg/kg IV weekly until disease progression. Neratinib: 240 mg taken by mouth daily until disease progression.
CetuximabDrug
Patients with HER2 WT or HER2 amplified with no prior anti-EGFR therapy: 400 mg/m2 IV loading dose; then 250 mg/m2 IV weekly. Neratinib 240 mg taken by mouth daily until disease progression.
NeratinibDrug
Also called Nerlynx
240 mg taken by mouth daily until disease progression.
Guardant360 Diagnostic TestDiagnostic test
Prior to assignment to Arm 1, the Guardant360 diagnostic test will be conducted in blood to confirm known HER2 status for select patients.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Guardant360 test on blood from select patients with known HER2 status.
Prior to assignment to Arm 1, HER2 test on blood obtained from Quadruple Wild-Type patients who received anti-EGFR therapy. Patients with HER2 amplified, HER2 Wild-Type or HER2 mutated will recieve:
• Neratinib daily + Trastuzumab weekly until disease progression Receives: Drug: Trastuzumab; Drug: Neratinib; Diagnostic Test: Guardant360 Diagnostic Test |
| Arm 2 | Experimental | Patients with HER2 Wild Type or HER2 amplified with no prior anti-EGFR therapy will receive:
• Neratinib daily + Cetuximab weekly until disease progression Receives: Drug: Cetuximab; Drug: Neratinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival with neratinib plus trastuzumab therapy
Progression free survival (PFS). Percentage of patients alive with absence of progression assessed using RECIST 1.1 criteria.
Measured: From initiation of neratinib plus trastuzumab therapy to time of tumor assessment, between cycle 6 and 7,which is usually six months after start of therapy.
Progression free survival (PFS) with neratinib plus cetuximab therapy
Progression free survival (PFS). Percentage of patients alive with absence of progression assessed using RECIST 1.1 criteria
Measured: From initiation of neratinib plus cetuximab therapy to time of tumor assessment between cycles 6 and 7, which is usually 6 months after start of therapy
Secondary outcomes (3)
Overall response rate to study therapy
Rate of best overall response using measurement of tumor in patients with measurable metastatic disease
Measured: From initiation of study therapy until disease progression, approximately 6 months.
Clinical benefit rate
Rate of disease status by continuous tumor measurement.
Measured: From initiation of study therapy until disease progression, approximately 6 months.
Frequency of adverse events assessed using CTCAE 4.0
Frequency of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0.
Measured: From beginning of study therapy until disease progression, approximately 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2018
- Study start18 May 2018
- Primary completion30 Sep 2021
- Study completion30 Sep 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NSABP Foundation Inc
- Sponsor type
- Research network
- Collaborators
- Puma Biotechnology, Inc.
- Responsible party
- Sponsor
- Investigators
- Norman Wolmark, MD, Principal investigator, NSABP Foundation Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03457896
- Sponsor's protocol ID
- NSABP FC-11
- Status last verified
- Mar 2022
- First submitted
- 1 Mar 2018
- Last updated
- 31 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Freeman TJ, George TJ, Jacobs SA, Yothers G, Kolevska T, Feng H, Lipchik C, Maley S, Song N, Srinivasan A, Finnigan M, Wade JL 3rd, Buchschacher GL Jr, Al Baghdadi T, Shipstone A, Lin D, Puhalla SL, Allegra CJ, Wolmark N, Pogue-Geile KL. NSABP FC-11: A phase II study of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (KRAS/NRAS/BRAF/PIK3CA) metastatic colorectal cancer based on HER2 status: amplified, non-amplified (wild-type), or mutated. Cancer Chemother Pharmacol. 2025 Aug 9;95(1):80. doi: 10.1007/s00280-025-04802-8.
PubMed 40782152
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study Evaluating the Combination of Neratinib Plus Trastuzumab or Neratinib Plus Cetuximab in Patients With "Quadruple Wild-Type" (KRAS/NRAS/BRAF/PIK3CA Wild-Type) Metastatic Colorectal Cancer Based on HER2 Status: Amplified, Non-Amplified (Wild-Type) or Mutated
- ClinicalTrials.gov ID
- NCT03457896
- Acronym / sponsor ID
- NSABP FC-11
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- NSABP, PUMA, Neratinib, Trastuzumab, Cetuximab, RAS, NRAS, BRAF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- NSABP Foundation IncResearch network
- Collaborators
- Puma Biotechnology, Inc.
- Study start
- 18 May 2018 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 30 Sep 2022 (estimated)
- First posted
- 8 Mar 2018 (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.
This is a phase II trial to examine the efficacy of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (all RAS/NRAS/BRAF/PIK3CA wild-type), metastatic colorectal cancer based on HER2 status (amplified, non-amplified [wild-type] or mutated). Patients must have confirmed quadruple wild-type (WT) genotype, via NSABP MPR-1 or from colonic biopsy or a metastatic biopsy taken prior to treatment, and known HER2 status.
Detailed description
The primary aim of this study is to determine the progression-free survival (PFS) in each of these HER2 populations. Secondary aims include overall response rate (ORR) and clinical benefit rate (CBR) defined as the objective tumor decrease and stable disease by RECIST 1.1 criteria; toxicity and safety profile. Exploratory analysis will be performed to assess for molecular predictors of response. The local site will make the primary determination of response and progression based on all radiographic images (e.g., MRI, CT, PET, bone scan, etc.) as well as other relevant reports documenting disease response or progression.
For patients identified as quadruple WT with prior cetuximab or panitumumab treatment, a pre-entry blood sample will be required from consenting patients to confirm HER2 amplification for study eligibility.
Patients with quadruple WT, HER2 amplified with prior anti-EGRF therapy and/or HER2 mutated colorectal cancer with/or without prior anti-EGRF therapy will receive concurrent therapy with trastuzumab 4 mg/kg IV loading dose followed by 2 mg/kg IV weekly and neratinib 240 mg taken by mouth daily until disease progression, (Arm 1).
Patients with quadruple WT, HER2 WT or HER2 amplified with no prior anti-EGRF therapy will be assigned to receive concurrent therapy with cetuximab (400 mg/m2 IV loading dose followed by 250 mg/m2 IV weekly), and neratinib 240 mg taken by mouth daily until disease progression (Arm 2).
Approximately thirty-five (35) patients will be accrued to this study; 15 patients with HER2 amplified, 15 patients with HER2 WT, and approximately 5 patients with HER2 mutated colorectal cancer. Patients with HER2 WT or HER2 amplified mCRC who drop out of the study before the first scan (for whatever reason) will be replaced. Patients who drop out of the study after the first scan but before the second scan will be considered to have progressive disease.
Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).
Required blood and tissue samples will be collected at entry into the study. A tumor biopsy will be procured from an accessible site of metastasis before study therapy is initiated (after the patient has signed the consent form and has been screened for eligibility). Tissue will be sent to Champions Oncology Laboratory for engraftment into an NOD/SCID mouse to develop a patient-derived xenograft (PDX) model, and to NSABP Pathology Division for correlative science. Tissue samples from PDX models will be sent to Celcuity for functional HER2 signaling assay. Additional blood samples will be collected during the course of treatment.
Optional tumor and blood samples will be collected from consenting patients at the time of disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Trastuzumab, Drug: Neratinib, Diagnostic Test: Guardant360 Diagnostic TestGuardant360 test on blood from select patients with known HER2 status. Prior to assignment to Arm 1, HER2 test on blood obtained from Quadruple Wild-Type patients who received anti-EGFR therapy. Patients with HER2 amplified, HER2 Wild-Type or HER2 mutated will recieve: • Neratinib daily + Trastuzumab weekly until disease progression |
| Arm 2 | Experimental | Drug: Cetuximab, Drug: NeratinibPatients with HER2 Wild Type or HER2 amplified with no prior anti-EGFR therapy will receive: • Neratinib daily + Cetuximab weekly until disease progression |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- The tumor tissue must have been determined to be KRAS, NRAS, BRAF, PIK3CA (all RAS quadruple) wild-type by CLIA testing.
- The ECOG performance status must be 0, 1 or 2. Patients must have the ability to swallow and retain oral medication. There must be documentation by CT scan, or MRI, that the patient has evidence of measurable metastatic disease per RECIST 1.1 criteria.
- Patients must have an accessible metastatic lesion for pretreatment core biopsy procurement.
- Unless either drug is medically contraindicated, patients must have received oxaliplatin and irinotecan as part of standard chemotherapy regimens. (This includes adjuvant therapy.)
- HER2 amplified confirmed by CLIA testing performed on blood samples, and prior treatment with cetuximab or panitumumab.
Key exclusion criteria (11 listed)
- Diagnosis of anal or small bowel carcinoma. Colorectal cancer histology other than adenocarcinoma, e.g., sarcoma, lymphoma, carcinoid.
- Previous therapy with any HER2 targeting agents (such as trastuzumab, lapatinib, neratinib, etc.) for any malignancy.
- Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms.
- Active hepatitis B or hepatitis C with abnormal liver function tests. Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
- Persistent CTCAE v4.0 greater than or equal to grade 2 diarrhea regardless of etiology.
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 with HER2 amplified tumors with prior anti-EGFR therapy and/or HER2 mutated colorectal cancer with/or without prior anti-EGFR therapy will receive 4 mg/kg IV loading dose; then 2 mg/kg IV weekly until disease progression. Neratinib: 240 mg taken by mouth daily until disease progression. | Drug | Arm 1 |
| CetuximabPatients with HER2 WT or HER2 amplified with no prior anti-EGFR therapy: 400 mg/m2 IV loading dose; then 250 mg/m2 IV weekly. Neratinib 240 mg taken by mouth daily until disease progression. | Drug | Arm 2 |
| NeratinibAlso: Nerlynx240 mg taken by mouth daily until disease progression. | Drug | Arm 1, Arm 2 |
| Guardant360 Diagnostic TestPrior to assignment to Arm 1, the Guardant360 diagnostic test will be conducted in blood to confirm known HER2 status for select patients. | Diagnostic test | Arm 1 |
Primary outcome
Progression free survival with neratinib plus trastuzumab therapy
Time frame: From initiation of neratinib plus trastuzumab therapy to time of tumor assessment, between cycle 6 and 7,which is usually six months after start of therapy.
Progression free survival (PFS). Percentage of patients alive with absence of progression assessed using RECIST 1.1 criteria.
Progression free survival (PFS) with neratinib plus cetuximab therapy
Time frame: From initiation of neratinib plus cetuximab therapy to time of tumor assessment between cycles 6 and 7, which is usually 6 months after start of therapy
Progression free survival (PFS). Percentage of patients alive with absence of progression assessed using RECIST 1.1 criteria
3 secondary outcomes
Overall response rate to study therapy
Time frame: From initiation of study therapy until disease progression, approximately 6 months.
Clinical benefit rate
Time frame: From initiation of study therapy until disease progression, approximately 6 months.
Frequency of adverse events assessed using CTCAE 4.0
Time frame: From beginning of study therapy until disease progression, approximately 6 months.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2022.
- Derived from this study: PubMed 40782152Freeman TJ, George TJ, Jacobs SA, Yothers G, Kolevska T, Feng H, Lipchik C, Maley S, Song N, Srinivasan A, Finnigan M, Wade JL 3rd, Buchschacher GL Jr, Al Baghdadi T, Shipstone A, Lin D, Puhalla SL, Allegra CJ, Wolmark N, Pogue-Geile KL. NSABP FC-11: A phase II study of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (KRAS/NRAS/BRAF/PIK3CA) metastatic colorectal cancer based on HER2 status: amplified, non-amplified (wild-type), or mutated. Cancer Chemother Pharmacol. 2025 Aug 9;95(1):80. doi: 10.1007/s00280-025-04802-8.
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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. This study is not recruiting at the moment.
Norman Wolmark, MD principal investigator
NSABP Foundation Inc
48 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, Cetuximab and Neratinib in people with Metastatic Colorectal Cancer, run by NSABP Foundation Inc at 48 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 19 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 31 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 48 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival with neratinib plus trastuzumab therapy (time frame: From initiation of neratinib plus trastuzumab therapy to time of tumor assessment, between cycle 6 and 7,which is usually six months after start of therapy.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03457896, which also lists 1 linked publication.
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 31 Mar 2022.