Capecitabine and 131I-huA33 in Patients With Metastatic Colorectal Cancer

NCT00291486 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: LUD2002-017R21CA108145-01A1
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this clinical trial is to determine whether it is safe to treat patients with advanced colorectal cancer, with humanised A33 antibody tagged with radioactive iodine (131I-huA33) in combination with chemotherapy (capecitabine).

Conditions

Colorectal Neoplasms

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Dose-Limiting Toxicities (DLT)

  Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3.0). DLT was defined as any of the following related events: Any grade 2 or greater allergic reaction related to huA33. Any grade ≥ 3 non-haematological toxicity related to 131I-huA33 or capecitabine. * These toxicities included palmar plantar erythema, but skin rash thought to be related to huA33 protein was not a DLT as previous studies have shown no relation of this toxicity to dose of huA33 or radioiodine dose. * Capecitabine cardiotoxicity grade ≥ 3 - including vasospasm, acute coronary syndrome and arrhythmia, necessitated the cessation of study drug in the affected patient but were not considered DLT as these are recognized as idiosyncratic in nature and not known to be related to capecitabine dose. Any grade ≥ 4 neutropenia ≥ 7 days in duration or any thrombocytopenia with a platelet count \< 10 x 10\^9/L.

  7 weeks

Secondary Outcomes (11)

• Number of Patients With Tumour Response Assessed by Response Evaluation Criteria in Solid Tumors (RECIST).

  13 weeks

• Biodistribution of 131I-huA33 Measured by Whole Body Clearance and Normal Organ Clearance Reported as Mean Biological Half-life (T1/2 Biological) After Initial 131I-huA33 Infusion

  1 week

• Mean Specific Absorbed Dose of 131I-huA33 for Normal Organs Calculated From the Initial Infusion

  1 week

• Mean Total Tumor Dose of 131I-huA33

  5 weeks

• Pharmacokinetics (PK) of 131I-huA33 as Measured by T½α and T½β (Half Lives of the Initial and Terminal Phases of Disposition, Respectively)

  5 weeks

Study Arms (5)

Cohort 1

EXPERIMENTAL

20 millicurie (mCi) 131I-huA33, 1500 mg/m2/day capecitabine All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0. This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Drug: Capecitabine; Drug: 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)

Cohort 2

EXPERIMENTAL

30 millicurie (mCi) 131I-huA33, 1500 mg/m2/day capecitabine All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0. This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Drug: Capecitabine; Drug: 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)

Cohort 3

EXPERIMENTAL

30 millicurie (mCi) 131I-huA33, 1000 mg/m2/day capecitabine All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0. This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Drug: Capecitabine; Drug: 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)

Cohort 4

EXPERIMENTAL

40 millicurie (mCi) 131I-huA33, 1000 mg/m2/day capecitabine All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0. This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Drug: Capecitabine; Drug: 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)

Cohort 5

EXPERIMENTAL

40 millicurie (mCi) 131I-huA33, 1250 mg/m2/day capecitabine All patients received an initial dose of 5 mg huA33 conjugated to 5-8 mCi 131I on day 0. This was followed 7 ± 2 days later by inpatient administration of a single infusion of 131I-huA33 with a constant protein dose of 10 mg/m2 huA33. Capecitabine was administered in 2 divided doses per day on days 1-14 of each 21-day cycle for a total of 4 cycles. Daily doses were rounded to the nearest 150 mg.

Drug: Capecitabine; Drug: 131I-huA33 (131-Iodine on humanised monoclonal antibody A33)

Interventions

Capecitabine DRUG

Capecitabine was administered orally at doses between 1000 and 1500 mg/m2/day depending on assigned dose level for 14 days per 21-day cycle. Daily doses were rounded to the nearest 150 mg.

Also known as: Xeloda

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

131I-huA33 (131-Iodine on humanised monoclonal antibody A33) DRUG

All patients received a dose of 5 mg huA33 conjugated to 5-8 mCi 131I. The therapy dose of 131I-huA33 comprised a constant protein dose of 10 mg/m2 huA33 regardless of dose level. The 131I-huA33 therapy dose was determined by the assigned dose level (i.e. 20, 30 or 40 mCi/m2 131I).

Cohort 1; Cohort 2; Cohort 3; Cohort 4; Cohort 5

Eligibility Criteria

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

You may qualify if:

• Metastatic colorectal cancer.
• Histologically or cytologically proven colorectal cancer.
• Measurable disease on CT scan with at least one lesion \>/= 2cm diameter (to allow adequate infusion imaging).
• Expected survival of at least 4 months.
• ECOG performance status 0-2.
• Vital laboratory parameters should be within normal range including:
• Neutrophils \>/= 1.5 x 10\^9/L;
• Platelets \>/= 150 x 10\^9/L;
• Serum bilirubin \</= 34 micromol/L;
• Calculated creatinine clearance \> 50 ml/min.
• Age \>/= 18 years.
• Able and willing to give valid written informed consent.

You may not qualify if:

• Previous treatment with capecitabine.
• Untreated active metastatic disease to the central nervous system (new or enlarging lesions on CT or MRI), or within 3 months of treatment (ie surgery or radiotherapy) for brain metastases.
• Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.
• Liver involvement with metastatic disease \> 50% liver volume.
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
• Previous external beam irradiation except if: (i) it was for standard adjuvant pelvic radiation for rectal cancer; (ii) it was for localised irradiation for skin cancer; or (iii) the sum total of all previous external beam irradiation port areas is not greater than 25% of the total red marrow.
• Previous treatment with a monoclonal antibody or antibody fragment AND a positive huA33 human anti-human antibody (HAHA) titre.
• Concomitant treatment with systemic corticosteroids. Topical or inhalational corticosteroids are permitted.
• Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
• Lack of availability of the patient for clinical and laboratory follow-up assessment.
• Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
• Pregnancy or breastfeeding.
• Women of childbearing potential: Refusal or inability to use effective means of contraception.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ludwig Institute Oncology Unit and Tumor Targeting Program, Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Related Publications (2)

• Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, Verweij J, Van Glabbeke M, van Oosterom AT, Christian MC, Gwyther SG. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000 Feb 2;92(3):205-16. doi: 10.1093/jnci/92.3.205.

  PMID: 10655437 BACKGROUND

• Herbertson RA, Tebbutt NC, Lee FT, Gill S, Chappell B, Cavicchiolo T, Saunder T, O'Keefe GJ, Poon A, Lee ST, Murphy R, Hopkins W, Scott FE, Scott AM. Targeted chemoradiation in metastatic colorectal cancer: a phase I trial of 131I-huA33 with concurrent capecitabine. J Nucl Med. 2014 Apr;55(4):534-9. doi: 10.2967/jnumed.113.132761. Epub 2014 Feb 20.

  PMID: 24556590 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Capecitabine

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)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• Prof. Andrew M Scott, MBBS, DDU MD

  Ludwig Institute for Cancer Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2006
• First Posted: February 14, 2006
• Study Start: October 1, 2003
• Primary Completion: January 3, 2008
• Study Completion: August 29, 2012
• Last Updated: October 10, 2022
• Results First Posted: January 11, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)