Phase 1
N=20
Phase I Trial of huA33 Plus Chemotherapy in Patients With Metastatic Colorectal Cancer
Colorectal Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00199797 ↗Enrolled (actual)
20
Serious AEs
55.0%
Results posted
Jun 2021
Primary outcome: Primary: 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. — 20; 17; 1; 18 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Oxaliplatin (Drug); 5-Fluorouracil (Drug); Leucovorin (Drug); huA33 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Ludwig Institute for Cancer Research
- Primary completion
- Nov 2006
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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. |
20; 17; 1; 18; 11 | — |
| SECONDARY 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. |
6; 14 | — |
| SECONDARY Tumor Response in Patients With Metastatic Colorectal Cancer Receiving huA33, Oxaliplatin and 5-FU Plus Leucovorin. |
1; 7; 4; 7 | — |
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.
Eligibility Criteria
Inclusion Criteria
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.
Exclusion Criteria
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.
- Women of childbearing potential: Refusal or inability to use effective means of contraception.
Data sourced from ClinicalTrials.gov (NCT00199797). 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.