Colorectal NeoplasmsPhase 1NCT01220999

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

A Phase 1 study testing CS-1008 in people with Colorectal Neoplasms, run by Ludwig Institute for Cancer Research at 1 site in Australia.

Completed

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

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Colorectal Neoplasms
What is being tested?: CS-1008
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteAustralia
Study dates: 12 Oct 2010to 27 Jun 2012
Phase: Phase 1
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

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.

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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

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

Ludwig Institute Tumor Targeting Program, Austin Health
Melbourne, Victoria, 3084

Other trials in Australia

About this study

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.

Read the detailed description

Eligible subjects were to be enrolled into one of 5 dose-escalation cohorts to receive CS-1008 administered weekly as an intravenous (IV) infusion over 30 ± 10 minutes. Each cohort initially comprised 2 subjects but was expanded in up to 5 subjects if additional biodistribution and/or PK data were required.

The initial infusion of CS-1008 on Day 1 was trace labeled with Indium-111 (111^In-CS-1008; 5-7 mCi) and was investigated at escalating doses up to the standard loading dose, as follows: Cohort 1 (0.2 mg/kg), Cohort 2 (1 mg/kg), Cohort 3 (2 mg/kg), Cohort 4 (4 mg/kg), and Cohort 5 (6 mg/kg). The initial 111^In-CS-1008 dose was followed by gamma camera imaging with blood sampling over a 10-day period to evaluate biodistribution, tumor uptake, PK, and serum biomarkers. Day 8 dosing comprised non-labeled CS-1008 at doses of 6 mg/kg in Cohorts 1-3, 4 mg/kg in Cohort 4, and 2 mg/kg in Cohort 5. Subsequent weekly infusions of standard dose CS-1008 (2 mg/kg) were administered on Days 15, 22, 29, 36, and 43. The Day 36 infusion of CS-1008 was also trace labeled with 111^In (5-7 mCi), with subsequent gamma camera imaging and blood sampling.

Subjects were assessed for disease status using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, serum tumor biomarkers (carcinoembryonic antigen [CEA]), and human-anti-CS-1008-antibody development (HAHA). Subjects were assessed for changes in tumor metabolism following CS-1008 administration using computed tomography (CT) or fluorodeoxyglucose positron emission tomography (18^F-FDG PET) scans.

Cycle 1 encompassed the first 7 weeks of therapy. Within 1 week (Days 44-50) after the last infusion of CS-1008, subjects completed an End of Study/End of Cycle 1 assessment. Subjects with stable disease or better (according to RECIST version 1.1) at the Day 44-50 reassessment were permitted to receive additional 4-week cycles of CS-1008 (2 mg/kg) until disease progression, unacceptable toxicity, or subject/physician decision.

Conditions: Colorectal Neoplasms
Being tested: CS-1008
Keywords: Clinical trial, CS-1008 mAb, monoclonal antibody CS-1008, Positron-Emission Tomography, Pharmacokinetics, Pharmacodynamics, apoptosis, caspases
Medical subject headings: Colorectal Neoplasms

What participants receive

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

CS-1008Drug
Also called Tigatuzumab
CS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).

Study groups in NCT01220999
Study group	Role	What they receive
Cohort 1	Experimental	Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment. Receives: Drug: CS-1008
Cohort 2	Experimental	Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment. Receives: Drug: CS-1008
Cohort 3	Experimental	Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment. Receives: Drug: CS-1008
Cohort 4	Experimental	Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment. Receives: Drug: CS-1008
Cohort 5	Experimental	Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment. Receives: Drug: CS-1008

What is being measured

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

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
Tumor localization was assessed using gamma camera imaging performed after the initial infusion of 111^In-CS-1008 on Day 1 and then on Days 2, 4/5, 7/8, and 11/12 (collectively, "After Day 1 Infusion" in the table) and after the second infusion of 111^In-CS-1008 on Day 36 and then on Days 37, 39/40, and 42/43 (collectively, "After Day 36 Infusion" in the table). Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.
Measured: Up to 43 days
Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions
Tumor localization was assessed using gamma camera imaging performed on Days 7/8 and 42/43. Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.
Measured: Up to 43 days
Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Measured: Up to 36 days
Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Measured: Up to 36 days
Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Measured: Up to 36 days
Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Measured: Up to 36 days
Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Measured: Up to 36 days
Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Measured: Up to 50 days
Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Measured: Up to 50 days
Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Measured: Up to 50 days
Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Measured: Up to 50 days
Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Measured: Up to 50 days

Secondary outcomes (2)

Number of Subjects With Best Overall Tumor Response
Tumor responses were evaluated using appropriate imaging and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1, at Screening, at the end of every odd-numbered cycle (i.e., Cycles 1, 3, and 5, as applicable), and at the time of treatment discontinuation. Per RECIST 1.1, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria (Eisenhauer et al. Eur J Cancer 2009;45:228-47).
Measured: Up to 7 months
Number of Subjects With Best Overall Metabolic Response
Metabolic response to CS-1008 was assessed by fluorodeoxyglucose positron emission tomography (18^F-FDG PET) at Screening, Day 15, and at the End of Cycle 1/End of Study visit (Days 44-50). For each FDG-PET performed, the maximum standardized uptake value (SUVmax) corrected for body weight for all target lesions >2 cm identified on CT imaging was calculated using region of interest (ROI). The ROI was determined with the aid of the anatomical detail provided by the CT scan. Tumor metabolic response to CS-1008 was assessed by 18^F-FDG PET/CT calculated using the target lesion with the greatest baseline SUVmax, and was categorized according to the European Organization for Research and Treatment of Cancer (EORTC) guidelines (Young et al. Eur J Cancer 1999;35:1773-82).
Measured: Up to 50 days

Timeline

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

12 Oct 201027 Jun 2012

First posted14 Oct 2010 (estimated)
Study start12 Oct 2010
Primary completion27 Jun 2012
Study completion27 Jun 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01220999
Sponsor's protocol ID: LUD2010-002
Status last verified: Oct 2022
First submitted: 12 Oct 2010
Last updated: 28 Oct 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
PubMed 19097774
Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
PubMed 10673991
Ciprotti M, Tebbutt NC, Lee FT, Lee ST, Gan HK, McKee DC, O'Keefe GJ, Gong SJ, Chong G, Hopkins W, Chappell B, Scott FE, Brechbiel MW, Tse AN, Jansen M, Matsumura M, Kotsuma M, Watanabe R, Venhaus R, Beckman RA, Greenberg J, Scott AM. Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2015 Aug 20;33(24):2609-16. doi: 10.1200/JCO.2014.60.4256. Epub 2015 Jun 29.
PubMed 26124477

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer
ClinicalTrials.gov ID: NCT01220999
Acronym / sponsor ID: LUD2010-002
Conditions: Colorectal Neoplasms
Keywords: Clinical trial, CS-1008 mAb, monoclonal antibody CS-1008, Positron-Emission Tomography, Pharmacokinetics, Pharmacodynamics, apoptosis, caspases
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Ludwig Institute for Cancer ResearchUniversity, hospital or other
Collaborators: Daiichi Sankyo
Study start: 12 Oct 2010 (actual)
Primary completion: 27 Jun 2012 (actual)
Study completion: 27 Jun 2012 (actual)
First posted: 14 Oct 2010 (estimated)
Results: Posted 23 Sep 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Cohort 1	Experimental	Drug: CS-1008Subjects received an initial loading dose of 111^In-CS-1008 (0.2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Cohort 2	Experimental	Drug: CS-1008Subjects received an initial loading dose of 111^In-CS-1008 (1 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Cohort 3	Experimental	Drug: CS-1008Subjects received an initial loading dose of 111^In-CS-1008 (2 mg/kg) on Day 1, CS-1008 (6 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Cohort 4	Experimental	Drug: CS-1008Subjects received an initial loading dose of 111^In-CS-1008 (4 mg/kg) on Day 1, CS-1008 (4 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.
Cohort 5	Experimental	Drug: CS-1008Subjects received an initial loading dose of 111^In-CS-1008 (6 mg/kg) on Day 1, CS-1008 (2 mg/kg) on Day 8, and subsequent weekly doses of CS-1008 (2 mg/kg) on Days 15, 22, 29, 36, and 43; the Day 36 dose was also radiolabeled with 111^In. Additional 4-week cycles of weekly CS-1008 (2 mg/kg) were permitted for subjects benefiting from treatment.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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.

Key exclusion criteria (10 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CS-1008Also: TigatuzumabCS-1008 was administered once weekly as an intravenous infusion over 30 ± 10 minutes at a dose range of 0.2 to 6 mg/kg. On Days 1 and 36, CS-1008 infusions were radiolabeled with 111^In (5-7 mCi).	Drug	Cohort 1, Cohort 2, Cohort 3, Cohort 4, Cohort 5

Primary outcome

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
Time frame: Up to 43 days
Tumor localization was assessed using gamma camera imaging performed after the initial infusion of 111^In-CS-1008 on Day 1 and then on Days 2, 4/5, 7/8, and 11/12 (collectively, "After Day 1 Infusion" in the table) and after the second infusion of 111^In-CS-1008 on Day 36 and then on Days 37, 39/40, and 42/43 (collectively, "After Day 36 Infusion" in the table). Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.
Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions
Time frame: Up to 43 days
Tumor localization was assessed using gamma camera imaging performed on Days 7/8 and 42/43. Dosimetry calculations were performed to determine the tumor localization properties of 111^In-CS-1008. Calculation of whole body dose and doses to individual organs by 111^In-CS-1008 were performed based on conjugate view images obtained from quantitative whole body images obtained at multiple time points. MIRD formalism was used in the calculation of doses.
Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Time frame: Up to 36 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Time frame: Up to 36 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Time frame: Up to 36 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Time frame: Up to 36 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008
Time frame: Up to 36 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 1 infusion at the following time points: Day 1 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 2 (24 hours after Day 1 infusion), Day 4/5, Day 7/8 (pre-infusion and 5 minutes post-infusion if on Day 8), Day 11/12, and Day 36 (pre-infusion).
Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Time frame: Up to 50 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Time frame: Up to 50 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Mean 111^In-CS-1008 Serum Area Under the Curve by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Time frame: Up to 50 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Mean 111^In-CS-1008 Serum Total Clearance by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Time frame: Up to 50 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).
Mean 111^In-CS-1008 Serum Maximum Concentration by Gamma Counting Following the Day 36 Infusion of 111^In-CS-1008
Time frame: Up to 50 days
The serum PK of CS-1008 was evaluated by gamma scintillation counting to assess serum radioactivity (111^In-CS-1008) and CS-1008 protein concentration following the Day 36 infusion at the following time points: Day 36 (pre-infusion and 5 minutes and 1, 2, and 4 hours post-infusion), Day 37 (24 hours after Day 36 infusion), Day 39/40, Day 43 (pre-infusion and 5 minutes post-infusion), and at the End of Cycle visit (Days 44-50).

2 secondary outcomes

Number of Subjects With Best Overall Tumor Response
Time frame: Up to 7 months
Number of Subjects With Best Overall Metabolic Response
Time frame: Up to 50 days

Results and safety

Results posted to the registry on 23 Sep 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Cohort 1	2	2
Cohort 2	4	4
Cohort 3	5	4
Cohort 4	3	3
Cohort 5	5	5

Primary outcome: 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

Time frame: Up to 43 days. Number. Unit: participants

Measure	Cohort 1 n = 2	Cohort 2 n = 4	Cohort 3 n = 5	Cohort 4 n = 3	Cohort 5 n = 5
After Day 1 infusion: High, Specific Uptake	0	3	3	3	3
After Day 1 infusion: No Uptake	2	1	2	0	2
After Day 36 infusion: High, Specific Uptake	0	3	3	3	3
After Day 36 infusion: No Uptake	2	1	1	0	2

Population analysed: The population comprises all subjects who completed study requirements through Cycle 1 (Day 43). One patient in Cohort 3 was prematurely withdrawn from the study on Day 36 due to symptomatic deterioration secondary to progressive disease (radiologically documented) and did not complete Cycle 1.

Primary outcome: Mean Tumor Uptake of 111^In-CS-1008 Based on Gamma Camera Imaging Following the Day 1 and Day 36 Infusions

Time frame: Up to 43 days. Mean (Standard Deviation). Unit: % of injected dose/g of organ

Measure	Cohort 1 n = 0	Cohort 2 n = 3	Cohort 3 n = 3	Cohort 4 n = 3	Cohort 5 n = 3
Post-infusion tumor uptake: Day 7/8	–	0.0042 (0.0013)	0.0063 (0.0004)	0.0044 (0.0015)	0.0043 (0.0006)
Post-infusion tumor uptake: Day 42/43	–	0.0045 (0.0005)	0.0061 (0.0011)	0.0044 (0.0012)	0.0036 (0.0007)

Population analysed: The population comprises all subjects who completed study requirements through Cycle 1 (Day 43) and had tumor uptake.

Primary outcome: Mean 111^In-CS-1008 Serum Half-life by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008

Time frame: Up to 36 days. Mean (Standard Deviation). Unit: hours

Measure	Cohort 1 n = 2	Cohort 2 n = 4	Cohort 3 n = 5	Cohort 4 n = 2	Cohort 5 n = 4
Initial half-life	14.51 (5.95)	21.52 (5.76)	5.29 (4.76)	10.45 (6.85)	14.73 (4.72)
Terminal half-life	284.76 (0.38)	264.89 (122.12)	163.08 (39.86)	243.39 (52.21)	247.5 (52.9)

Population analysed: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

Primary outcome: Mean 111^In-CS-1008 Serum Volume of Central Compartment by Gamma Counting Following the Day 1 Infusion of 111^In-CS-1008

Time frame: Up to 36 days. Mean (Standard Deviation). Unit: mL

Measure	Cohort 1 n = 2	Cohort 2 n = 4	Cohort 3 n = 5	Cohort 4 n = 2	Cohort 5 n = 4
Value	3209.83 (321.96)	2592.36 (303.21)	3329.11 (624.49)	2658.70 (112.60)	4037 (425)

Population analysed: The population comprises all subjects who received Day 1 of study treatment and had post-infusion PK samples evaluable by gamma scintillation counting.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs that occurred or worsened in severity after the first dose of study treatment were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 7 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Cohort 1	0 of 2 (0%)	2 of 2 (100%)	0 of 2
Cohort 2	0 of 4 (0%)	2 of 4 (50%)	0 of 4
Cohort 3	3 of 5 (60%)	3 of 5 (60%)	0 of 5
Cohort 4	1 of 3 (33.3%)	3 of 3 (100%)	0 of 3
Cohort 5	0 of 5 (0%)	4 of 5 (80%)	0 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19097774Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.
Background: PubMed 10673991Young H, Baum R, Cremerius U, Herholz K, Hoekstra O, Lammertsma AA, Pruim J, Price P. Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999 Dec;35(13):1773-82. doi: 10.1016/s0959-8049(99)00229-4.
Results publication: PubMed 26124477Ciprotti M, Tebbutt NC, Lee FT, Lee ST, Gan HK, McKee DC, O'Keefe GJ, Gong SJ, Chong G, Hopkins W, Chappell B, Scott FE, Brechbiel MW, Tse AN, Jansen M, Matsumura M, Kotsuma M, Watanabe R, Venhaus R, Beckman RA, Greenberg J, Scott AM. Phase I Imaging and Pharmacodynamic Trial of CS-1008 in Patients With Metastatic Colorectal Cancer. J Clin Oncol. 2015 Aug 20;33(24):2609-16. doi: 10.1200/JCO.2014.60.4256. Epub 2015 Jun 29.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Andrew M Scott, MBBS, MD, FRACP, DDU principal investigator

Ludwig Institute for Cancer Research & Austin Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CS-1008 in people with Colorectal Neoplasms, run by Ludwig Institute for Cancer Research at 1 site in Australia.

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 13 inclusion and 10 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 28 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 1 site in Australia. 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 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.

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 23 Sep 2019). 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?

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 (time frame: Up to 43 days). The study lists 12 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 NCT01220999, which also lists 3 linked publications.

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 28 Oct 2022.