Palbociclib and Cetuximab in Metastatic Colorectal Cancer

NCT03446157 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC1717
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is designed to provide a better understanding of study drugs cetuximab (Erbitux®) and palbociclib when used in combination to treat patients with metastatic colon cancer.

Conditions

Colon Cancer; Cancer of the Colon; Colon Neoplasms; Colonic Cancer; Neoplasms, Colonic

Keywords

colon cancer; metastatic colon cancer; palbociclib; cetuximab

Outcome Measures

Primary Outcomes (1)

• Disease Control Rate

  Overall Response Rate (ORR) = CR + PR Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed assessed by Positron Emission Tomography (PET)- Computerized tomography (CT) scans. If the subject experienced a Complete Response (CR), the disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), no response or less response than Partial or Progressive; or Progressive Disease (PD), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion new lesion.

  4 months

Secondary Outcomes (4)

• Overall Response Rate

  4 months (Cycle 5)

• Length of Overall Survival

  Up to 20 months

• Length of Progression Free Survival

  Up to 20 months

• Number of Participants With Grade 3 and Grade 4 Adverse Events

  From day 1 of treatment until grade 3 or 4 events occurred. (Up to 20 monts)

Study Arms (1)

Open-label, single arm, Phase II

EXPERIMENTAL

Cetuximab and palbociclib

Drug: Cetuximab; Drug: Palbociclib

Interventions

Cetuximab DRUG

Loading dose on day 1 of week 1 of 400 mg/m2 via IV over 2 hours Subsequent doses of 250 mg/m2 via IV over 1 hour weekly for 4 weeks (28 days) in combination with palbociclib

Also known as: Erbitux

Open-label, single arm, Phase II

Palbociclib DRUG

125 mg taken orally once daily on days 1-21, then 7 days off

Also known as: Ibrance

Open-label, single arm, Phase II

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2
• Histologically-confirmed metastatic CRC
• Measurable disease according to RECIST v1.1 for solid tumors.
• Documented wild-type in KRAS and NRAS (codons 12, 13, 59, 61, 117, and 146) and in BRAF codon 600, based on tumor tissue taken from primary or metastatic site and tested for biomarkers
• Previously treated with at least two prior regimens of systemic chemotherapy for metastatic or locally advanced, unresectable disease, including fluoropyrimidines (5-fluorouracil and/or capecitabine), oxaliplatin, and irinotecan.
• A maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment For patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy with fluoropyrimidine and oxaliplatin, only one regimen of systemic chemotherapy for metastatic disease is required
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained prior to initiating study medications.
• System Laboratory Value Hematological\* Hemoglobin (Hgb) ≥ 9 g/dL Absolute Neutrophil Count (ANC) ≥ 1500/mm3 Platelets ≥ 100,000/mm3
• Renal\* Creatinine OR Calculated creatinine clearance ≤1.5 x ULN
• mL/min by Cockcroft-Gault formula Hepatic\* Bilirubin ≤ 1.0 × upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤ 3 × ULN OR
• × ULN (if liver metastases present) Alanine aminotransferase (ALT) ≤ 3 × ULN OR
• × ULN (if liver metastases present)
• Note: Hematology and other lab parameters that are ≤ grade 2 BUT still meet criteria for study entry are allowed. Furthermore, changes in laboratory parameters during the study should not be considered adverse events unless they meet criteria for dose modification(s) of study medication outlined by the protocol and/or worsen from baseline during therapy.

You may not qualify if:

• Active infection requiring systemic therapy.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Presence of known, active central nervous system (CNS) metastases.
• Treatment with any investigational drug within 28 days prior to initiating study medications.
• Prior treatment with drug targeting cyclin-dependent kinase (CDK) family.
• Subject is receiving prohibited medications or treatments as listed in section 5.5 of the protocol that cannot be discontinued/replaced by an alternative therapy.
• Known hypersensitivity to the components of study drugs or analogs of study drugs.
• Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Uncontrolled, severe concomitant comorbidity (e.g. uncontrolled hypertension, uncontrolled diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, active or uncontrolled infection).
• History of interstitial lung disease or pneumonitis.
• Any other clinically significant heart disease, including angina pectoris, resting bradycardia, left bundle branch block, ventricular tachyarrhythmia, unstable atrial fibrillation, acute myocardial infarction, or heart disease requiring cardiac pacemaker or implantable cardioverter/defibrillator
• Known psychiatric or substance abuse disorder that would interfere with the ability of the patient to comply with trial requirements.
• History of long-QT syndrome.
• Baseline QTcF ≥ 470 msec.
• Concomitant use of drugs known to cause QT prolongation as defined in Appendix 12.4 and in section 5.5 (Note: Ondansetron at doses ≤ 16 mg or less is allowed)

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Amgen: collaborator
• Pfizer: collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Publications (3)

• Sorah JD, Moore DT, Reilley MJ, Salem ME, Triglianos T, McRee AJ, Lee MS, Sanoff HK, Somasundaram AS. Phase II single-arm study of palbociclib and cetuximab in anti-EGFR naive patients with KRAS/NRAS/BRAF wild-type, metastatic colorectal cancer. Oncologist. 2025 Oct 1;30(10):oyaf305. doi: 10.1093/oncolo/oyaf305.

  PMID: 40990835 DERIVED

• Sorah JD, Moore DT, Reilley MJ, Salem ME, Triglianos T, Sanoff HK, McRee AJ, Lee MS. Phase II Single-Arm Study of Palbociclib and Cetuximab Rechallenge in Patients with KRAS/NRAS/BRAF Wild-Type Colorectal Cancer. Oncologist. 2022 Dec 9;27(12):1006-e930. doi: 10.1093/oncolo/oyac222.

  PMID: 36288238 DERIVED

• Noh JY, Lee IP, Han NR, Kim M, Min YK, Lee SY, Yun SH, Kim SI, Park T, Chung H, Park D, Lee CH. Additive Effect of CD73 Inhibitor in Colorectal Cancer Treatment With CDK4/6 Inhibitor Through Regulation of PD-L1. Cell Mol Gastroenterol Hepatol. 2022;14(4):769-788. doi: 10.1016/j.jcmgh.2022.07.005. Epub 2022 Jul 15.

  PMID: 35843546 DERIVED

Related Links

• UNC Lineberger

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Cetuximab; palbociclib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Melahat Canter
• Organization: University of North Carolina Lineberger Comprehensive Cancer Center

Melahat_Canter@med.unc.edu

919-445-4208

Study Officials

• Hanna Sanoff

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, single-arm, phase II clinical trial of combination therapy with cetuximab and palbociclib in refractory KRAS, NRAS, and BRAF wild-type metastatic colorectal cancer (CRC) patients

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: February 26, 2018
• Study Start: March 23, 2018
• Primary Completion: May 29, 2023
• Study Completion: January 26, 2026
• Last Updated: March 10, 2026
• Results First Posted: August 7, 2024

Record last verified: 2026-02

Locations

US (1)