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Recurrent Colorectal CarcinomaPhase 1/2NCT02713373

Cetuximab and Pembrolizumab in Treating Patients With Colorectal Cancer That is Metastatic or Cannot Be Removed by Surgery

A Phase 1/2 study testing Cetuximab, Laboratory Biomarker Analysis and Pembrolizumab in people with Recurrent Colorectal Carcinoma and Stage IVA Colorectal Cancer, run by Roswell Park Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I/II trial studies the side effects and best dose of cetuximab when given together with pembrolizumab in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) or that cannot be removed by surgery. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cetuximab, Laboratory Biomarker Analysis and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
2 sitesUnited States
Study dates
5 Aug 2016to 20 Jul 2021
Phase
Phase 1/2
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

  • Have a pathologically confirmed diagnosis of colorectal cancer, which is metastatic or otherwise unresectable
  • Have received at least 1 prior systemic therapy in the metastatic or unresectable disease setting; patients who have recurred within six months of adjuvant chemotherapy are not required to have received an additional line of chemotherapy
  • Retrovirus-associated deoxyribonucleic acid (DNA) sequence (RAS) wild-type; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing must be completed, with full KRAS and neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) testing strongly advised; the presence of known mutations in KRAS or NRAS is exclusionary; primary tumor or metastatic tumor may be tested; (note: in the case of multiple genomic evaluations with conflicting results - e.g. KRAS mutant in one sample, but wild-type in another - the patient may be included as RAS wild-type, if clinically justified, after review with the principal investigator [PI])
  • Appropriate for anti-EGFR therapy: Naive to anti-EGFR therapy (cetuximab or panitumumab) or a candidate for rechallenge by virtue of the following:
  • the investigator deems anti-EGFR retreatment with cetuximab to be a reasonable standard of care option AND
  • outcome of prior anti-EGFR therapy was not rapid progression (i.e. <= 3 months on therapy) AND
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  • prior anti-EGFR therapy was administered > 6 months prior to the start of protocol therapy
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria present
  • Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion; newly-obtained is defined as a specimen obtained up to 30 days prior to initiation of treatment on day 1
  • Hemoglobin >= 8 g/dL (performed within 14 days of treatment initiation)
  • Absolute neutrophil count >= 1000/mm3 (performed within 14 days of treatment initiation)
  • Platelet count >= 100,000/mm3 (performed within 14 days of treatment initiation)
  • Serum creatinine =< 2 upper limit of normal (ULN) or, >= 15 mL/min for participants with creatinine levels > 2 ULN (performed within 14 days of treatment initiation)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 ULN or, =< 5 ULN for participants with liver metastases (performed within 14 days of treatment initiation)
  • Female participants of childbearing potential are to have a negative serum pregnancy test
  • Female participants of child-bearing potential must agree to use an acceptable method of birth control, be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
  • Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
  • Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Who cannot join

  • Participants who have had chemotherapy, targeted therapies, radiotherapy, or used an investigational device within 2 weeks prior to the first dose of treatment or those who have not recovered from adverse events (i.e., =< grade 1 or at baseline) due to agents administered more than 2 weeks earlier; note: participants with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients
  • Prior severe infusion reaction to cetuximab
  • Has a known additional malignancy that requires active treatment; exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
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  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment; this exception does not include carcinomatous meningitis which is excluded regardless of clinical stability
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment
  • Has known history of, or any evidence of active, non-infectious pneumonitis
  • Uncontrolled clinically significant intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness, substance abuse disorders or social situations that would limit compliance with study requirements
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
  • Has a known history of human immunodeficiency virus (HIV or HIV 1/2 antibodies); testing not required
  • Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected); testing not required
  • Has received a live vaccine within 30 days of planned start of study therapy (note: seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and shingles are not allowed)
  • Received an investigational agent within 30 days prior to starting study treatment
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Unwilling or unable to follow protocol requirements

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University Hospitals Seidman Cancer Center

    Cleveland, Ohio, 44106

Other trials in United States

About this study

Official title: A Phase Ib/II Study of Cetuximab and Pembrolizumab in Metastatic Colorectal Cancer

This phase I/II trial studies the side effects and best dose of cetuximab when given together with pembrolizumab in treating patients with colorectal cancer that has spread from the primary site (place where it started) to other places in the body (metastatic) or that cannot be removed by surgery. Monoclonal antibodies, such as cetixumab and pembrolizumab, may block tumor growth in different ways by targeting certain cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the objective response rate of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

II. To estimate the 6-month progression free survival (PFS) rate of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

III. To examine the adverse event profile of combining pembrolizumab and cetuximab.

SECONDARY OBJECTIVES:

  1. To examine the PFS of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

II. To determine the objective response rate by immune-related response criteria (irRC) of patients with metastatic colorectal cancer.

III. To examine the overall survival of patients with metastatic colorectal cancer treated with pembrolizumab and cetuximab.

EXPLORATORY OBJECTIVES:

  1. Identify tumor and peripheral blood biomarkers of response and/or resistance to the study treatment.

OUTLINE:

Patients receive cetuximab intravenously (IV) over 120 minutes on day 1, 8, and 15 (as monotherapy for cycle 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression.

After completion of the study treatment, patients are followed up every 3 months for up to 2 years.

Being tested
Cetuximab, Laboratory Biomarker Analysis, Pembrolizumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CetuximabBiological

    Also called Chimeric Anti-Epidermal Growth Factor Receptor (EGFR) Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

Study groups in NCT02713373
Study groupRoleWhat they receive
Arm I (cetuximab and pembrolizumab)ExperimentalPatients receive cetuximab IV over 120 minutes on day 1 (days 1, 7, and 14 of course 1 only) and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 3 weeks for 24 months in the absence of disease progression or unacceptable toxicity. Patients may continue pembrolizumab treatment for up to 1 year if they experience disease progression.
Receives: Biological: Cetuximab; Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To Examine the Adverse Event Profile

    The frequency of toxicities will be tabulated by maximum grade by preferred term within a patient across all cycles.

    Measured: up to 24 months

  2. Progression Free Survival (PFS), Evaluated According to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1

    Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), At least a 20% increase in the sum of diameters of target lesions, taking as references the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.

    Measured: At 6 months

  3. Number of Participants With a Response, Evaluated According to RECIST 1.1

    Number of Participants with a Response, Evaluated According to RECIST 1.1 will be tabulated and will be compared to the null values using exact tests.

    Measured: Up to 2 years

Secondary outcomes (3)

  1. Objective Tumor Response Using Immune-related RECIST

    tumor response using immune-related RECIST (irRECIST) will be tabulated, summarized and reported.

    Measured: up to 24 months

  2. Overall Survival (OS)

    Distributions of OS will be estimated using the Kaplan-Meier method.

    Measured: Up to death, withdrawal of consent, or the end of the study, whichever occurs first, assessed up to 2 years

  3. Progression Free Survival (PFS)

    Distributions of PFS will be estimated using the Kaplan-Meier method. Median PFS is reported.

    Measured: Up to15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2016 (estimated)
  2. Study start5 Aug 2016
  3. Primary completion28 Jul 2020
  4. Study completion20 Jul 2021

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02713373
Sponsor's protocol ID
I 274515
Other IDs
NCI-2016-00228, I 274515, P30CA016056
Status last verified
Sep 2022
First submitted
11 Mar 2016
Last updated
6 Oct 2022
Data monitoring committee
Yes

Publications

  • Fountzilas C, Rosario S, Witkiewicz AK, Withers HG, Bajor DL, Mukherjee S, Saltzman J, Maguire O, Minderman H, Chatley S, Tarquini ML, Whitworth A, Jurcevic J, Hsiao HH, Knudsen ES, Muhitch JB, Abrams SI, Kalinski P, Segal BH, Bakin A, Yuan G, Wang C, Attwood K, Iyer R, Boland PM. TP53 mutation is associated with improved disease control in patients with advanced RAS wild-type colorectal adenocarcinoma treated with cetuximab and pembrolizumab. Int J Cancer. 2026 Jun 15;158(12):3300-3311. doi: 10.1002/ijc.70434. Epub 2026 Mar 7.

    PubMed 41793309

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cetuximab, Laboratory Biomarker Analysis and Pembrolizumab in people with Recurrent Colorectal Carcinoma and Stage IVA Colorectal Cancer, run by Roswell Park Cancer Institute 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 19 inclusion and 17 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: finished, as of the sponsor's last update on 6 Oct 2022. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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 3 Dec 2021). 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?

To Examine the Adverse Event Profile (time frame: up to 24 months). The study lists 3 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 NCT02713373, 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 6 Oct 2022.

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