Phase 1 Completed N=19 Treatment

A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer

Source: ClinicalTrials.gov NCT01220999 ↗

Enrolled (actual)

Serious AEs

21.1%

Results posted

Sep 2019

Primary outcomePrimary: Number of Subjects With Tumor Uptake of 111^In-CS-1008 in Target Lesions Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions — 0; 3; 3; 3 participants

Summary

This was a Phase 1, open-label, single-center study of CS-1008, an immunoglobulin G subclass 1 (IgG1) humanized monoclonal antibody, in subjects with advanced colorectal carcinoma who had received ≥ 1 prior chemotherapy regimen for metastatic disease. Primary study objectives were to determine the influence of the CS-1008 dose on the biodistribution, pharmacokinetics (PK) and tumor uptake of radiolabeled CS-1008 following a single infusion and following continuous sequential doses of CS-1008. Secondary objectives were to evaluate changes in tumor metabolism, antitumor response, and changes in serum apoptosis biomarkers and tumor response markers following treatment with CS-1008.

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Subjects With Tumor Uptake of 111^In-CS-1008 in Target Lesions Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions	0; 3; 3; 3; 3; 2	—
PRIMARY Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions	0.0042; 0.0063; 0.0044; 0.0043; 0.0045; 0.0061	—
PRIMARY Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008	14.51; 21.52; 5.29; 10.45; 14.73; 284.76	—
PRIMARY Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008	3209.83; 2592.36; 3329.11; 2658.70; 4037	—
PRIMARY Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008	986.58; 5706.38; 8386.68; 18714.05; 28492	—
PRIMARY Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008	14.92; 12.31; 18.23; 12; 18.52	—
PRIMARY Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008	4.59; 24.6; 47.29; 84.14; 131.3	—
PRIMARY Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008	12.21; 15.84; 15.01; 15.56; 186.2; 247.5	—
PRIMARY Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008	2510; 3272; 2742; 3985	—
PRIMARY Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008	9013; 9772; 10990; 10465	—
PRIMARY Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008	14.11; 15.29; 10.73; 19.00	—
PRIMARY Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008	51.08; 47.10; 40.98; 47.38	—
SECONDARY Number of Subjects With Best Overall Tumor Response	0; 0; 0; 1; 0; 1	—
SECONDARY Number of Subjects With Best Overall Metabolic Response	0; 0; 0; 1; 0; 1	—

Eligibility Criteria

Inclusion Criteria

Histologically proven metastatic colorectal cancer with 1 target lesion ≥ 2 cm and evaluable by gamma camera imaging. If this lesion was previously irradiated, progression must have been documented following radiotherapy.
Received at least 1 prior course of chemotherapy for metastatic disease.
Expected survival of at least 3 months.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Age ≥ 18 years old.
Able and willing to give valid written informed consent.
Within the last 1 week prior to first study drug administration, laboratory parameters for vital functions were to be in the normal range. Laboratory abnormalities that were not clinically significant were generally permitted, except for the following laboratory parameters, which were to be within the ranges specified:
Neutrophil count: ≥ 1.5 x 10^9/L
Platelet count: ≥ 90 x 10^9/L
International normalized ratio: ≤ 1.5
Serum bilirubin: ≤ 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT): ≤ 2 x ULN (≤ 5 x ULN if liver metastases)
Calculated creatinine clearance (Cockcroft-Gault formula): ≥ 55 mL/min

Exclusion Criteria

Active central nervous system metastases. Definitively treated metastases were allowed if stable for 6 weeks off therapy.
Known immunodeficiency or human immunodeficiency virus positivity.
Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, or any condition that in the opinion of the Investigator would have interfered with the ability of the subject to fulfill the study requirements.
Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to first study drug administration, that in the opinion of the Investigator had >10% risk of relapse within 12 months.
Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to first study drug administration.
Regular corticosteroid, nonsteroidal anti-inflammatory drug (NSAID) (other than paracetamol or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to first drug administration. Intermittent dosing of corticosteroid or NSAID was permitted if less than 4 doses within a 3-day period.
Mental impairment that may have compromised the ability to give informed consent and comply with the requirements of the study.
Lack of availability for clinical follow-up assessments.
Pregnancy or breastfeeding.
Women of childbearing potential: refusal or inability to use effective means of contraception.

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Data sourced from ClinicalTrials.gov (NCT01220999). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.