Image Guided Treatment Optimization With Cetuximab for Patients With Metastatic Colorectal Cancer

NCT02117466 | Terminated Phase 1 DMC

• 2 other identifiers: 2013.2652013-002023-41
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 3

Brief Summary

In this study the investigators will evaluate the uptake of 89Zirconium labeled cetuximab in extra-hepatic colorectal metastases. The investigators hypothesize that uptake of 89Zr-cetuximab is required for response to cetuximab. If no uptake is present the investigators will escalate the dose cetuximab and repeat the 89Zr-cetuximab PET. The investigators will evaluate the clinical benefit rate of cetuximab in the patients with and without uptake. The ultimate goal is to create a selection tool that can predict response of cetuximab.

Conditions

Metastatic Colorectal Cancer

Keywords

cetuximab; PET-imaging

Outcome Measures

Primary Outcomes (2)

• Uptake (SUV) of 89Zr-cetuximab in extra-hepatic metastases on PET-scan

  6 days post injection

• Clinical Benefit Rate

  Complete response, partial response and stable disease (according to RECIST 1.1) on CT-scan (every 2 months)

  From date of first cetuximab injection until the date of first documented progression (median time to progression 2.5 months)

Secondary Outcomes (6)

• Early response evaluation with 18F-FDG PET

  two weeks after start treatment

• Tumor perfusion as early response evaluation (measured with 15O-H2O-PET)

  two weeks after start treatment

• Overall survival

  From date first cetuximab injection until the date of death (median overall survival 10 months)

• Progression Free Survival

  From date of first cetuximab injection until the date of first documented progression (median time to progression 2.5 months)

• Skin toxicity and hypomagnesemia as early response marker

  From date of first cetuximab injection until the date of first documented progression (median time to progression 2.5 months)

Study Arms (2)

Standard dose cetuximab

OTHER

Uptake of 89Zr-cetuximab: continue standard dose (500mg/m2 bsa) (standard care)

Drug: Standard dose cetuximab

Dose escalation cetuximab

EXPERIMENTAL

No 89Zr-cetuximab uptake: dose escalation in a 3x3 cohort design (with maximal 50% dose increase each cohort; with a maximum of 2000 mg/m2 bsa every two weeks)

Drug: Dose escalation cetuximab

Interventions

Dose escalation cetuximab DRUG

dose escalation of cetuximab (described in the second arm)

Dose escalation cetuximab

Standard dose cetuximab DRUG

500mg/m2 bsa cetuximab (described in the first arm)

Standard dose cetuximab

Eligibility Criteria

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

You may qualify if:

• Subjects are eligible if they meet the following criteria:
• Advanced colorectal adenocarcinoma
• Subjects must have been treated according to standard care with palliative chemotherapy including a fluoropyrimidine (e.g. fluorouracil or capecitabine), irinotecan, and oxaliplatin or had contra-indications to treatment with these drugs.
• No local treatment options
• Life expectancy of at least 12 weeks.
• Age =\> 18 years.
• Histological or cytological documentation of cancer is required.
• Tumor material must be tested wild type for the K-RAS (codon 12, 13, 61, 117, 146) and N-RAS (codon 12, 13, 61, 117, 146) genes.
• Subjects have at least one measurable lesion ≥ 2 cm outside the liver. Lesions must be evaluable by CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• ECOG (Eastern Cooperative Oncology Group) Performance Status of 0, 1 or 2
• Adequate liver and renal functions as assessed by the following laboratory requirements to be conducted within 7 days prior to start of treatment:
• Total bilirubin ≤ 1.5 times the upper limit of normal
• ALT (alanine aminotransferase) and AST (aspartate aminotransferase) ≤ 2.5 times upper limit of normal (≤ 5 times upper limit of normal for subjects with liver involvement of their cancer)
• Serum creatinin ≤ 1.5 times upper limit of normal or a calculated creatinin clearance =\> 50 ml/min
• Signed informed consent must be obtained prior to any study specific procedures.

You may not qualify if:

• Subjects who meet the following criteria at the time of screening will be excluded:
• Previous exposure to an anti-EGFR therapy
• Significant skin condition interfering with treatment
• Pregnant or breast-feeding subjects. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must agree to use adequate barrier birth control measures (e.g., cervical cap, condom, and diaphragm) during the course of the trial. Oral birth control methods alone will not be considered adequate on this study, because of the potential pharmacokinetic interaction between study drug and oral contraceptives. Concomitant use of oral and barrier contraceptives is advised. Contraception is necessary for at least 6 months after receiving study drug.
• Concurrent anticancer chemotherapy, immunotherapy or investigational drug therapy during the study or within 4 weeks of the start of study drug.
• Radiotherapy to the target lesions during study or within 4 weeks of the start of study drug. Palliative radiotherapy will be allowed.
• Major surgery within 28 days of start of study drug.
• Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results.
• Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study.

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead
• University Medical Center Groningen: collaborator
• Radboud University Medical Center: collaborator

Study Sites (3)

Radboud University Medical Centre Nijmegen

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

VU medical centre

Amsterdam, 1007 MB, Netherlands

Location

University Medical Centre Groningen

Groningen, 9700 RB, Netherlands

Location

Related Publications (3)

• Tabernero J, Ciardiello F, Rivera F, Rodriguez-Braun E, Ramos FJ, Martinelli E, Vega-Villegas ME, Rosello S, Liebscher S, Kisker O, Macarulla T, Baselga J, Cervantes A. Cetuximab administered once every second week to patients with metastatic colorectal cancer: a two-part pharmacokinetic/pharmacodynamic phase I dose-escalation study. Ann Oncol. 2010 Jul;21(7):1537-1545. doi: 10.1093/annonc/mdp549. Epub 2009 Nov 25.

  PMID: 19940007 BACKGROUND

• Wahl RL, Jacene H, Kasamon Y, Lodge MA. From RECIST to PERCIST: Evolving Considerations for PET response criteria in solid tumors. J Nucl Med. 2009 May;50 Suppl 1(Suppl 1):122S-50S. doi: 10.2967/jnumed.108.057307.

  PMID: 19403881 BACKGROUND

• Van Cutsem E, Tejpar S, Vanbeckevoort D, Peeters M, Humblet Y, Gelderblom H, Vermorken JB, Viret F, Glimelius B, Gallerani E, Hendlisz A, Cats A, Moehler M, Sagaert X, Vlassak S, Schlichting M, Ciardiello F. Intrapatient cetuximab dose escalation in metastatic colorectal cancer according to the grade of early skin reactions: the randomized EVEREST study. J Clin Oncol. 2012 Aug 10;30(23):2861-8. doi: 10.1200/JCO.2011.40.9243. Epub 2012 Jul 2.

  PMID: 22753904 BACKGROUND

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Oncologist

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 21, 2014
• Study Start: April 1, 2014
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: April 14, 2021

Record last verified: 2021-04

Locations

NL (3)