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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.

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

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.

5-Fluorouracil

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

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

huA33

Christoph Renner, MD

Alexander Knuth, MD

Elke Jäger, MD

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.

Purpose of the Research Study:

huA33 is an antibody that reacts with the A33 antigen which is produced by colorectal cancers. Prior studies have shown that application of the huA33 antibody may delay the growth of tumor cells producing the respective antigen.

Oxaliplatin and 5-FU are cytotoxic agents which are considered as standard treatment in metastatic colorectal cancer. Leucovorin is a vitamin which enhances the effect of 5-FU.

The primary purpose of this study is to determine whether the combination huA33 plus oxaliplatin, 5-FU and leucovorin is safe and what side effects occur.

Description of Research Procedures:

The first step is to determine whether or not patients are eligible for participation in the study. Apart from general blood tests and x-ray studies needed, this involves testing with regard to some special requirements:

* Three tests of stool to determine if it is positive for blood.
* Women of childbearing age must have a negative pregnancy test.
* If patients ever had a treatment with similar substances like huA33 before, a blood sample needs to be tested for antibodies that may have developed against huA33.

After eligibility is established, huA33 will be administered intravenously over a period of 30 minutes once a week at a dose of 10 mg/m2. Starting on day 15 and continuing every second week, oxaliplatin, 5-FU and leucovorin are administered. Oxaliplatin and leucovorin will be given as infusions over 2 hours. Afterwards patients will receive a bolus infusion of 5-FU intravenously followed by an infusion of 5-FU over 22 hours.

The doses of oxaliplatin will be 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 consists of 12 weekly treatment days.

Patients will have an interview with their doctor and a physical examination before the first day of treatment and before each therapy. Standard blood tests as well as special blood tests to measure a possible reaction of the immune system to the huA33 antibody will be done weekly and before the treatment is started. The amount of blood to be drawn will be 20-30 ml during one cycle of the study.

X-rays and/or CT scans to measure the extent of the disease will be done at the start and at week 13, which is considered to be the first day of the next cycle. Patients may continue with this treatment for up to 2 cycles.

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

Phase I Trial of huA33 Plus 5-fluorouracil (5-FU), Leucovorin and Oxaliplatin 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.

Serum samples were taken at baseline and prior to each administration of huA33.The samples were analyzed by surface plasmon resonance technology using a BIACORE 2000 instrument. All sera were analyzed at the end of the study. Patient serum was considered HAHA positive if the response unit (RU) value at a serum dilution of 1:100 exceeded a cutoff value, defined as the mean inter-patient baseline RU value + 3x the standard deviation (SD) of negative control sera at a serum dilution of 1:100. Results were reported as either positive or negative.

Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse P et al. J Natl Cancer Inst 92: 205-216 2000) at baseline and at the end of each cycle.

Per RECIST, target lesions were 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.

Ludwig Institute for Cancer Research

All adverse events which occurred after signing informed consent were documented in the source records and on the respective case report form, regardless of the assumption of a causal relationship. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Scale (Version 3.0).Treatment emergent adverse events (TEAEs) are any adverse events occurring or worsening after the first administration of study drug.

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.

huA33 Antibody Plus Chemotherapy

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 an 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.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Switzerland

Germany

Region of Enrollment

All patients who received at least one dose of huA33.

Jonathan Skipper PhD

Number of patients with treatment emergent adverse events

Number of patients with treatment emergent adverse events Grade 3 or above

Number of patients with treatment emergent adverse events which resulted in death

Number of patients with treatment emergent adverse events related to treatment

Number of patients with serious adverse events

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.

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 an 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.

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.

Patients who received huA33 and were evaluable for response. One patient was not evaluable.

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

Overall Study

Carcinoma

Anti-Infective Agents

Iodine

Cadexomer iodine

Altretamine

Patients will receive a single I-V infusion of 4mCi-10mCi/10mg 124I-huA33 in 5-30 mL of 5% human serum albumin (HAS) in normal saline, over 5 minutes-4 hours. Patients will be studied with 124I-huA33 positron-emission tomography (PET) and ex-vivo quantitation of tumor uptake .

Blood samples will be obtained for pharmacokinetic analysis at 5, 15, 60, and 120 minutes after completion of IV, on and before or after PET scanning on subsequent days.

Surgery (or biopsy) will be scheduled to occur 8- 10 days after administration of 124I-huA33. The 8-10 day imaging session will be scheduled for the morning of surgery or biopsy, approximately 1-6 hours before the procedure.

Patients will receive a single intravenous or intraarterial infusion of 10mg huA33, labeled with 4mCi-10mCi of 124I in 5-30ml of 5% HSA in normal saline (NS), over 5-10 minutes. On study days 2, 3, and/or 4 patients will have the option to receive up to 2g/kg of IVIG. Patients will be evaluated with 124I-huA33 positron-emission tomography (PET) with ex vivo quantitation of tumor uptake.

Iodine-124 labeled humanized A33 (antibody)

Neeta Pandit-Taskar, MD

The purpose of this study is to determine whether our drug, 124I-huA33, can safely detect colorectal cancer.

This is an open-label, pilot study of a single 4mCi-10mCi/10mg IV dose of 124I-huA33 in patients with colorectal cancer. Patients will be studied with 124I-huA33 positron-emission tomography (PET), and in the subset of patients scheduled for surgery, based on clinical indications, ex vivo quantitation of tumor uptake will also be performed. Patients will receive a single intravenous or intraarterial infusion of 4 mCi-10mCi /10mg 124I-huA33 in 5-30ml of 5% human serum albumin (HSA), over 5-10 minutes. Patient will either receive the 124I-huA33 intravenously (IV) or intraarterially (IA) to determine if there is an advantage of the IV vs the IA route. Following injection with 124I-huA33, on study days 2, 3, and/ or 4, patients will have the option to receive up to 2g/1kg of Immune Globulin (IVIG).

Blood samples will be obtained for pharmacokinetic analysis at 5, 15, 60, and 120 minutes after completion of IV or IA infusion, on day 2, 3, and/ or 4, and before and after the PET scan on the day of surgery or last imaging day (day 8 + 3). Patients scheduled for surgery will undergo a PET scan of the abdomen and pelvis 1-6 hours prior to surgery.

In those patients undergoing surgery, surgery (or biopsy) will be scheduled to occur day 8 (± 3 days) days after administration of 124I-huA33. Biopsy sites may include tumor, tumor bed, regional nodes, portal, suprapancreatic, celiac nodes and the retroperitoneum. Tumor and normal tissue obtained at surgery (or biopsy), and serum will be measured for estimation of percent-injected dose per gram of tumor, normal liver, and serum. Tissue samples will be obtained for autoradiography and immunohistochemistry as an additional assessment of tumor targeting.

Blood samples to determine immunogenicity will be taken at baseline and at 4 weeks.

Toxicity assessments will be made throughout the study period.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Trial of huA33 Plus Chemotherapy in Patients With Metastatic Colorectal Cancer	NCT00199797	Colorectal Canc...	Oxaliplatin 5-Fluorouracil Leucovorin huA33	18 Years -	Ludwig Institute for Cancer Research
Safety Study of Radio-labeled huA33 Antibody in Colorectal Cancer	NCT00199862	Colorectal Neop... Colorectal Canc... Colorectal Tumo... COlorectal Carc...	Iodine-124 labe...	18 Years -	Memorial Sloan Kettering Cancer Center
Safety Study of Radio-labeled huA33 Antibody in Colorectal Cancer	NCT00199862	Colorectal Neop... Colorectal Canc... Colorectal Tumo... COlorectal Carc...	Iodine-124 labe...	18 Years -	Memorial Sloan Kettering Cancer Center

Spots Global Cancer Trial Database for hua33

Every month we try and update this database with for hua33 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hua33

Every month we try and update this database with for hua33 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hua33 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.