Colorectal CancerPhase 2APK MutantNCT04853043
Cetuximab in Third Line for Mutant APC, TP53 and RAS Patients With Refractory Metastatic Colorectal Cancer
A Phase 2 study testing Cetuximab in people with Colorectal Cancer, run by University of Utah at 2 sites in United States.
Trial summary
A prospective, multi-center, phase II study of 21 patients to evaluate the efficacy of the epidermal growth factor receptor (EGFR) inhibitor, Cetuximab in patients with metastatic colorectal cancer (mCRC) harboring Adenomatous polyposis coli (APC), tumor protein p53 (TP53) and RAS mutations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Nov 2021to 3 May 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Male or female subject aged ≥ 18 years.
- Histologically confirmed metastatic colorectal adenocarcinoma with mutant APC, TP53 and KRAS genes as determined by the local Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory are eligible. All RAS mutations are allowed (KRAS, Neuroblastoma RAS (NRAS), HRAS). Patients with wild type KRAS, APC or TP53 are ineligible.
- Progression or unwanted toxicities on at least 2 prior lines of treatment including 5-Fluorouracil, oxaliplatin and irinotecan-based regimen
- Study participants must have measurable disease by RECIST 1.1 criteria by CT or MRI.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
- Study participants with treated and/or stable brain metastases are allowed
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- Study participants must have anticipated life expectancy > 3 months
- Adequate organ function as defined as:
- Hematologic:
- Absolute neutrophil count (ANC) ≥ ≥1000/µL
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dL
- Hepatic:
- Serum Bilirubin ≤ 2 x ULN or ≤ 3 x ULN for subjects with Gilbert's syndrome
- Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3.0 times the upper limit of normal (ULN; or 5.0 times the ULN in the setting of liver metastases)
- Renal:
- Serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
- For female subjects: Negative pregnancy test or evidence of post-menopausal status. The post-menopausal status will be defined as having been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:
- Women < 50 years of age:
- Amenorrheic for ≥ 12 months following cessation of exogenous hormonal treatments; and
- Luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution; or
- Underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
- Women ≥ 50 years of age:
- Amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments; or
- Had radiation-induced menopause with last menses >1 year ago; or
- Had chemotherapy-induced menopause with last menses >1 year ago; or
- Underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy, or hysterectomy).
- Female subjects of childbearing potential and male subjects with a sexual partner of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 12 months after last study treatment administration.
- Male subjects must agree to use a condom during intercourse for the duration of study therapy and for at least 12 months after last study treatment administration.
- Recovery to baseline or ≤ Grade 1 CTCAE v5.0 from toxicities related to any prior cancer therapy, unless considered clinically not significant by the treating investigator.
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.
Who cannot join
- Prior use of systemic anti-EGFR therapy including cetuximab or panitumumab is not allowed but prior use irinotecan, oxaliplatin, regorafenib or Trifluridine/Tipiracil (TAS-102) is allowed
- Study participants with prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen, as determined by the investigator
- Study participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease who need immediate central nervous system (CNS)-specific treatment during first cycle of treatment as determined by the treating physician.
- --Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
- Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
- The patient has clinically relevant coronary artery disease or history of myocardial infarction in the last 12 months or high risk of uncontrolled arrhythmia or uncontrolled cardiac insufficiency.
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- The patient has uncontrolled or poorly-controlled hypertension (>180 mmHg systolic or > 130 mmHg diastolic.
- Any other condition that would, in the Investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures (e.g., infection/inflammation, intestinal obstruction, unable to swallow medication, [subjects may not receive the drug through a feeding tube], social/ psychological issues, etc.)
- Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment.
- --Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.
- Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination, radiographic findings, and tuberculosis (TB) testing in line with local practice), hepatitis B (known positive hepatitis B virus (HBV) surface antigen (HBsAg) result), or hepatitis C.
- --Note: Subjects with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody (anti-HBc) and absence of HBsAg) are eligible. Subjects positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
- Medical, psychiatric, cognitive, or other conditions that may compromise the subject's ability to understand the subject information, give informed consent, comply with the study protocol or complete the study.
- Known prior severe hypersensitivity attributed to compounds of chemical or biologic composition similar to those of cetuximab, or if the patient had red meat allergy/tick bite history (NCI CTCAE v5.0 Grade ≥ 3).
- Live attenuated and inactive vaccinations within 4 weeks of the first dose of study treatment and while on trial is prohibited. Coronavirus Disease 19 (COVID-19) vaccines are allowed
- The patient is pregnant or breast-feeding.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Intermountain Medical Center
Salt Lake City, Utah, 84107
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: APK Mutant: A Single Arm Phase II Study of Cetuximab in Third Line for Mutant APC, TP53 and RAS Patients With Refractory Metastatic Colorectal Cancer
A prospective, multi-center, phase II study of 21 patients to evaluate the efficacy of the epidermal growth factor receptor (EGFR) inhibitor, Cetuximab in patients with metastatic colorectal cancer (mCRC) harboring Adenomatous polyposis coli (APC), tumor protein p53 (TP53) and RAS mutations.
- Conditions
- Colorectal Cancer
- Being tested
- Cetuximab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Cetuximab will be administered every 2 weeks (14 days). The initial dose of 500 mg/m2 is to be administered by IV infusion over 120 minutes on the first day of the treatment. In the absence of infusion reactions, subsequent doses are to be administered over 60 minutes biweekly. Each cycle will be defined as 14 days of treatment.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab | Experimental | Not described Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
Evaluate the PFS among patients treated with cetuximab in APC, TP53 and RAS mutated refractory metastatic colorectal cancer.
PFS will be measured from the date of first dose of study drug until the first documented radiographic evidence of disease progression by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) criteria 1.1, clinical progression per investigator judgement, start of new anti-cancer therapy, or death from any cause.
Per RECIST 1.1 for target lesions, Progressive Disease (PD) is a >=20% increase in the sum of the longest diameter (LD) of target lesions.
Disease progression by RECIST 1.1 is PD.
Measured: PFS will be measured from the date of first dose of study drug until first documented clinical or radiographic evidence of disease progression by RECIST 1.1, clinical progression, start of new therapy or death. Estimated assessment at 6 months.
Secondary outcomes (1)
Overall Survival (OS).
Evaluate the overall survival (OS) among patients treated with cetuximab in APC, TP53 and RAS mutated refractory metastatic colorectal cancer.
Upon discontinuation of study therapy, subjects will be followed for survival from the date of study therapy initiation until death, end of the study, or subject withdrawal of consent, whichever comes first.
Measured: OS was measured from the date of first dose of study drug until death from any cause (up to 223 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2021
- Study start3 Nov 2021
- Primary completion20 Feb 2024
- Study completion3 May 2024
Why it stopped: PI Determination - Slow recruitment, funding concerns, poor response to treatment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for 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
- Not applicable
- Intervention model
- Single group
- Model description
- Single arm, open label
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Vaia Florou, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04853043
- Sponsor's protocol ID
- HCI141689
- Other IDs
- R21CA252436
- Acronym
- APK Mutant
- Status last verified
- Apr 2025
- First submitted
- 16 Apr 2021
- Last updated
- 6 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- APK Mutant: A Single Arm Phase II Study of Cetuximab in Third Line for Mutant APC, TP53 and RAS Patients With Refractory Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT04853043
- Acronym / sponsor ID
- APK Mutant / HCI141689
- Conditions
- Colorectal Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI Determination - Slow recruitment, funding concerns, poor response to treatment
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 3 Nov 2021 (actual)
- Primary completion
- 20 Feb 2024 (actual)
- Study completion
- 3 May 2024 (actual)
- First posted
- 21 Apr 2021 (actual)
- Results
- Posted 6 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A prospective, multi-center, phase II study of 21 patients to evaluate the efficacy of the epidermal growth factor receptor (EGFR) inhibitor, Cetuximab in patients with metastatic colorectal cancer (mCRC) harboring Adenomatous polyposis coli (APC), tumor protein p53 (TP53) and RAS mutations.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single arm, open label
| Arm | Type | Receives |
|---|---|---|
| Cetuximab | Experimental | Drug: Cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Male or female subject aged ≥ 18 years.
- Histologically confirmed metastatic colorectal adenocarcinoma with mutant APC, TP53 and KRAS genes as determined by the local Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory are eligible. All RAS mutations are allowed (KRAS, Neuroblastoma RAS (NRAS), HRAS). Patients with wild type KRAS, APC or TP53 are ineligible.
- Progression or unwanted toxicities on at least 2 prior lines of treatment including 5-Fluorouracil, oxaliplatin and irinotecan-based regimen
- Study participants must have measurable disease by RECIST 1.1 criteria by CT or MRI.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
Key exclusion criteria (16 listed)
- Prior use of systemic anti-EGFR therapy including cetuximab or panitumumab is not allowed but prior use irinotecan, oxaliplatin, regorafenib or Trifluridine/Tipiracil (TAS-102) is allowed
- Study participants with prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of the investigational regimen, as determined by the investigator
- Study participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease who need immediate central nervous system (CNS)-specific treatment during first cycle of treatment as determined by the treating physician.
- --Note: Brain metastases or cranial epidural disease adequately treated with radiotherapy and/or surgery and stable for at least 4 weeks before the first dose of study treatment will be allowed on trial. Subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of the first dose of study treatment.
- Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
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 |
|---|---|---|
| CetuximabCetuximab will be administered every 2 weeks (14 days). The initial dose of 500 mg/m2 is to be administered by IV infusion over 120 minutes on the first day of the treatment. In the absence of infusion reactions, subsequent doses are to be administered over 60 minutes biweekly. Each cycle will be defined as 14 days of treatment. | Drug | Cetuximab |
Primary outcome
Progression Free Survival (PFS)
Time frame: PFS will be measured from the date of first dose of study drug until first documented clinical or radiographic evidence of disease progression by RECIST 1.1, clinical progression, start of new therapy or death. Estimated assessment at 6 months.
Evaluate the PFS among patients treated with cetuximab in APC, TP53 and RAS mutated refractory metastatic colorectal cancer. PFS will be measured from the date of first dose of study drug until the first documented radiographic evidence of disease progression by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) criteria 1.1, clinical progression per investigator judgement, start of new anti-cancer therapy, or death from any cause. Per RECIST 1.1 for target lesions, Progressive Disease (PD) is a >=20% increase in the sum of the longest diameter (LD) of target lesions. Disease progression by RECIST 1.1 is PD.
1 secondary outcome
Overall Survival (OS).
Time frame: OS was measured from the date of first dose of study drug until death from any cause (up to 223 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Vaia Florou, MD principal investigator
Huntsman Cancer Institute
2 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 Cetuximab in people with Colorectal Cancer, run by University of Utah at 2 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 31 inclusion and 16 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: stopped early, as of the sponsor's last update on 6 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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?
Yes. Results are posted in the registry (first posted 6 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 (PFS) (time frame: PFS will be measured from the date of first dose of study drug until first documented clinical or radiographic evidence of disease progression by RECIST 1.1, clinical progression, start of new therapy or death. Estimated assessment at 6 months.). 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 6 May 2025.