Utomilumab, Cetuximab, and Irinotecan Hydrochloride in Treating Patients With Metastatic Colorectal Cancer

NCT03290937 | Completed Phase 1 FDA Drug

• 3 other identifiers: 2017-0180NCI-2018-01036P30CA016672
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the best dose and side effects of irinotecan hydrochloride when given with utomilumab and cetuximab in treating patients with colorectal cancer that has spread to other places in the body (metastatic). Monoclonal antibodies, such as utomilumab and cetuximab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as irinotecan hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving utomilumab, cetuximab, and irinotecan hydrochloride may work better in treating patients with colorectal cancer.

Conditions

Stage IVA Colorectal Cancer AJCC v8; Stage IVB Colorectal Cancer AJCC v8; Stage IVC Colorectal Cancer AJCC v8; Metastatic Colorectal Carcinoma; Stage IV Colorectal Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose of irinotecan hydrochloride (Dose escalation)

  A modified 3+3 design will be used to determine the maximum tolerated dose.

  Up to 4 years

• Objective response rate (Dose expansion)

  Assessed by using the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST).

  Up to 4 years

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 4 years

• Progression free survival

  Up to 4 years

• Overall survival

  Up to 4 years.

• Overall response rate

  Up to 4 years

• Duration of response

  Up to 4 year

Study Arms (1)

Treatment (irinotecan hydrochloride, cetuximab, utomilumab)

EXPERIMENTAL

Patients receive irinotecan hydrochloride IV over 90 minutes and cetuximab IV over 1-2 hours on days 1 and 15, and utomilumab IV over 1 hour on day 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Cetuximab; Drug: Irinotecan Hydrochloride; Other: Pharmacodynamic Study; Biological: Utomilumab

Interventions

Pharmacodynamic Study OTHER

Correlative studies

Also known as: PHARMACODYNAMIC

Treatment (irinotecan hydrochloride, cetuximab, utomilumab)

Utomilumab BIOLOGICAL

Given IV

Also known as: PF 05082566, PF 5082566, PF-05082566, PF-2566

Treatment (irinotecan hydrochloride, cetuximab, utomilumab)

Cetuximab BIOLOGICAL

Given IV

Also known as: Cetuximab Biosimilar CDP-1, Cetuximab Biosimilar CMAB009, Cetuximab Biosimilar KL 140, Chimeric Anti-EGFR Monoclonal Antibody, Chimeric MoAb C225, Chimeric Monoclonal Antibody C225, Erbitux, IMC-C225

Treatment (irinotecan hydrochloride, cetuximab, utomilumab)

Irinotecan Hydrochloride DRUG

Given IV

Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E

Treatment (irinotecan hydrochloride, cetuximab, utomilumab)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically and or cytologically confirmed metastatic colorectal cancer
• Patients must have a wild type or mutated RAS tumor status known prior to enrollment
• Metastatic colorectal cancer patients have progressed following at least one line of fluorouracil (5-FU)-based chemotherapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Patients must have measurable disease per irRECIST criteria for part 2 (dose expansion)
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L (1,000/uL)
• Platelet count \>= 75 x 10\^9/L (75000/L)
• Hemoglobin \>= 8.0 g/dL (\>= 5.0 mmol/L)
• Patients must be transfusion independent (i.e., no blood product transfusions for a period of at least 14 days prior to screening)
• Serum creatinine \< 2 x upper limit of normal (ULN) or estimated creatinine clearance \> 30 ml/min as calculated using the method standard for the institution
• Total serum bilirubin \< 1.5 x ULN, unless the patient has documented Gilbert syndrome
• Aspartate and Alanine Aminotransferase (AST and ALT) \< 3 x ULN
• Left ventricular ejection fraction (LVEF) that is greater than 40%, or the absence of New York Heart Association (NYHA) classification of greater than stage II congestive heart failure
• Resolved acute effects of any prior therapy to baseline severity or grade =\< 2 Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 4.03 except for adverse events (AEs) not constituting a safety risk by investigator judgment
• Serum or urine pregnancy test (for females of childbearing potential) negative at screening and at the baseline visit (before the patient may receive the investigational product)

You may not qualify if:

• Patients with known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they are asymptomatic or have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable
• Patient has had any treatment specific for tumor control within 3 weeks of dosing, or for investigational drugs and cytotoxic agents, within 5 half-lives or 3 weeks, whichever is shorter
• Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 complex. Lists including medications and substances known or with the potential to interact with the CYP3A4 isoenzymes
• Prior therapy with a compound of the same mechanism as PF-05082566 (immunomodulation of 4-1BB)
• Major surgery within 28 days of starting study treatment
• Radiation therapy within 14 days of starting study treatment
• Autoimmune disorders (e.g., Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus) and other diseases that compromise or impair the immune system except patients who have grade 1 psoriasis (in remission or controlled with topical steroids) or mild degree of autoimmune thyroiditis that are controlled with medications
• Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness (HIV testing is not required)
• Unstable or serious concurrent medical conditions in the previous 6 months, e.g., pancreatitis, severe/unstable angina, prolonged QT interval corrected by Fridericia's formula (QTcF) \> 470 msec (calculated as average of triplicate readings, taken no greater than 2 minutes apart, and no history of torsades de pointes or symptomatic corrected QT \[QTc\] abnormality), symptomatic congestive heart failure, myocardial infarction and/or pulmonary hypertension, ongoing maintenance therapy for life-threatening ventricular arrhythmia, stroke, and uncontrolled major seizure disorder
• Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix
• Patients who are pregnant or breastfeeding
• Patients with intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins, or patients who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients)
• Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Irinotecan; utomilumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• David S Hong

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: December 27, 2017
• Primary Completion: December 30, 2025
• Study Completion: December 30, 2025
• Last Updated: January 6, 2026

Record last verified: 2026-01

Locations

US (1)