Phase I Trial of huA33 Plus Chemotherapy in Patients With Metastatic Colorectal Cancer

NCT00199797 | Completed Phase 1 Results

• 1 other identifier: LUD2003-005
• Study Type: interventional
• Target: 20
• Locations: 2 countries
• Sites: 2

Brief Summary

Although treatment for metastatic colorectal cancer has improved significantly over the recent years, it still remains a significant health problem representing the leading cancer by incidence in the United States of America. In the search for new therapies, monoclonal antibodies have been developed to specifically target human colon cancer cells. huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior studies have shown that administration of the huA33 antibody may delay the growth of tumor cells producing the specific antigen. Oxaliplatin and 5-fluorouracil (5-FU) are cytotoxic agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin (folinic acid) is a vitamin which enhances the effect of 5-FU. Eligible patients with advanced colorectal cancer will receive huA33 10 mg/m2 by intravenous (IV) infusion weekly for twelve weeks. Starting on Study Day 15 (week 3), 5-FU, leucovorin, and oxaliplatin will be administered every 2 weeks for 10 weeks. Patients will be evaluated weekly for toxicity. Blood samples will be obtained every week for hematology and serum biochemistry analysis and for determination of human anti-human antibodies (HAHA). In patients with measurable disease, tumors will be assessed by the appropriate scan at baseline and at the end of the thirteen week cycle. The primary objective of this study is to assess the safety of huA33 + 5-FU + leucovorin + oxaliplatin. The secondary objective is to measure the immunogenicity of huA33 when given in combination with 5-FU plus leucovorin and oxaliplatin and to document tumor responses.

Conditions

Colorectal Cancer

Keywords

Colorectal Cancer; huA33; antibody; chemotherapy

Outcome Measures

Primary Outcomes (1)

• Safety as Measured by the Number of Patients With Treatment Emergent Adverse Events (TEAEs), Grade 3 TEAEs, TEAEs Resulting in Death, TEAEs Related to Treatment and Serious TEAEs in Patients With Metastatic Colorectal Cancer.

  Patients were evaluated weekly for toxicity. Blood samples were obtained every week for hematology and serum biochemistry analysis. All adverse events, which occurred after the signing of informed consent were documented in the case report form. Toxicity was evaluated according to the National Cancer Institute CTCAE Scale (Version 3.0). All AEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 13.1 and classified by MedDRA system organ class (SOC) and preferred term. Treatment emergent adverse events (TEAEs) are any adverse events occurring or worsening after the first administration of study drug.

  up to 26 weeks

Secondary Outcomes (2)

• Immunogenicity of huA33 as Measured by the Number of Patients With Human Anti-human Antibodies (HAHA) When Given huA33 Together With Oxaliplatin and 5-FU Plus Leucovorin in Patients With Metastatic Colorectal Cancer.

  up to 26 weeks

• Tumor Response in Patients With Metastatic Colorectal Cancer Receiving huA33, Oxaliplatin and 5-FU Plus Leucovorin.

  up to 26 weeks

Study Arms (1)

huA33 antibody plus chemotherapy

EXPERIMENTAL

huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2 for 12 weeks. Starting on day 15 and continuing every second week, oxaliplatin, 5-fluorouracil (5-FU) and leucovorin were also administered. Oxaliplatin and leucovorin were given as infusions over 2 hours. Afterwards, patients received a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours. The doses of oxaliplatin were 85mg/m2, leucovorin 200mg/m2, 400mg/m2 of 5-FU as a bolus infusion and 600mg/m2 as a continuous infusion. A complete treatment cycle consisted of 12 weeks. Patients were eligible to receive an additional cycle in the absence of dose-limiting toxicity (DLT), immunogenicity (huA33 human anti-human antibodies {HAHA}) and disease progression.

Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: huA33

Interventions

Oxaliplatin DRUG

Oxaliplatin was administered at 85 mg/m2 on day 2 of every 2 week regimen.

Also known as: Eloxatin

huA33 antibody plus chemotherapy

5-Fluorouracil DRUG

The dose of 5-FU was 400 mg/m2 IV bolus followed by continuous IV infusion at 600 mg/m2 over 22 hours on day 2 and day 3 of every 2 week regimen.

Also known as: 5-FU

huA33 antibody plus chemotherapy

Leucovorin DRUG

Leucovorin was administered at a dose of 200mg/m2 on day 2 and day 3 of every 2 week regimen.

Also known as: folinic acid

huA33 antibody plus chemotherapy

huA33 DRUG

huA33 was administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2.

huA33 antibody plus chemotherapy

Eligibility Criteria

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

You may qualify if:

• Patients will be eligible for enrollment if they fulfill all of the following criteria:
• Metastatic colorectal cancer.
• Histologically or cytologically proven colorectal cancer.
• Expected survival of at least 4 months.
• Not more than 2 different pretreatment regimens.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Within the 2 weeks prior to the first dose of huA33, the following vital laboratory parameters:
• Lab Parameter Range
• Neutrophil count ≥ 1.5 x 10E9/L
• Platelet count ≥ 150 x 10E9/L
• Serum bilirubin ≤ 2 mg/dL
• Creatinine clearance \>50 ml/ min
• Age ≥ 18 years.
• Able and willing to give valid written informed consent.

You may not qualify if:

• Patients will be excluded from the study for any of the following reasons:
• Untreated active metastatic disease to the central nervous system defined as new or enlarging lesions on CT or MRI.
• Surgery or radiotherapy of brain metastases within 3 months prior to the first dose of huA33.
• Metastatic disease involving \> 50% of liver volume.
• Other serious illnesses, eg, serious infections requiring antibiotics, bleeding disorders.
• Chemotherapy, radiation therapy, or immunotherapy within 4 weeks prior to first dosing (6 weeks for nitrosoureas).
• Previous treatment with oxaliplatin.
• Previous treatment with huA33 monoclonal antibody or antibody fragment.
• a. Positive huA33 HAHA titer - defined as greater than 3 standard deviations above the mean patient normal range by Biacore analysis.
• Concomitant treatment with systemic corticosteroids. Topical or inhalational corticosteroids are permitted.
• Known HIV, Hepatitis B or C positivity.
• 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 first dosing.
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead

Study Sites (2)

Krankenhaus Nordwest

Frankfurt, 60488, Germany

Location

UniversitaetsSpital Zuerich

Zurich, CH-8091, Switzerland

Location

Related Publications (1)

• 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

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Fluorouracil; Leucovorin

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)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Results Point of Contact

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

jskipper@lcr.org

12124501539

Study Officials

• Christoph Renner, MD

  Universitätsspital Zürich, Switzerland

  PRINCIPAL INVESTIGATOR

• Alexander Knuth, MD

  Universitätsspital Zürich, Switzerland

  PRINCIPAL INVESTIGATOR

• Elke Jäger, MD

  Krankenhaus Nordwest, Germany

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: April 18, 2005
• Primary Completion: November 8, 2006
• Study Completion: April 1, 2016
• Last Updated: October 10, 2022
• Results First Posted: June 16, 2021

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); CH (1)