Colorectal Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer
Brief summary
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have advanced colorectal cancer.
Detailed description
OBJECTIVES: * Determine the toxicity, maximum tolerated dose, and pharmacokinetics of monoclonal antibody hu3S193 in patients with advanced colorectal carcinoma. * Determine the immune response in these patients treated with this regimen. OUTLINE: This is a dose escalation study. Patients receive monoclonal antibody hu3S193 (mAb hu3S193) IV over 30 minutes to 4 hours weekly for 8 weeks followed by 2 weeks of rest. Patients with stable or responding disease at week 10 receive maintenance mAb hu3S193 weekly. Courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of mAb hu3S193 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 3 of 6 patients experience dose limiting toxicities.
Interventions
BIOLOGICALmonoclonal antibody hu3S193
Sponsors
Ludwig Institute for Cancer Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically proven stage IV colorectal carcinoma. * Failed or refused conventional chemotherapy. * Lewis Y antigen present on more than 50% of tumor cells. * Measurable or evaluable disease. * No central nervous system (CNS) tumor involvement. * Karnofsky 80-100%. * Life expectancy: At least 6 weeks. * Granulocyte count greater than 1,500/mm\^3. * Platelet count greater than 100,000/mm\^3. * Bilirubin no greater than 1.0 mg/dL. * Prothrombin time less than 3 times upper limit of normal. * Creatinine no greater than 1.4 mg/dL. * Female patients of childbearing age and male patients must be asked to use effective contraception during the study. * At least 4 weeks since other prior immunotherapy.
Exclusion criteria
* New York Heart Association class III or IV heart disease. * Serious infection requiring antibiotics or other serious illness. * Pregnancy or nursing. * History of bleeding gastric ulcers or pancreatitis. * Diabetes mellitus requiring insulin. * Human antimouse antibodies (HAMA). * No prior mouse monoclonal antibody or antibody fragments. * Illness requiring the use of steroids or other anti-inflammatory agents. * Positive anti-hu3S193 antibody (HAHA) titer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Dose-limiting Toxicities (DLTs) | up to 10 weeks. | Toxicity was graded in accordance with the Common Toxicity Scale developed by NCI (1998) where Grade 1 represents the lowest toxicity grade and Grade 5 death. Dose-limiting toxicity (DLT) was defined as Grade 3 and Grade 4 adverse events which were at least possibly related to study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Tumor Responses | 8 weeks | Complete response (CR); disappearance of all measurable disease lasting a minimum of 4 weeks. Partial Response (PR); 50% or greater decrease in the sum of the products of the perpendicular diameters or all measurable lesions, without development of new lesions or increase in size of any lesion, lasting a minimum of 4 weeks. Progressive disease (PD); Appearance of new lesions or increase by 25% or more in size of any measurable lesion. Stable disease (SD); Not meeting criteria for response or progression. |
Countries
United States
Participant flow
Recruitment details
Seven patients were entered into the 10mg/m2 dose cohort. No patients were entered into the other cohorts as the study was terminated due to poor recruitment.
Participants by arm
| Arm | Count |
|---|---|
| Hu3S193 10 mg/m2 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. | 7 |
| Hu3S193 25 mg/m2 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. | 0 |
| Hu3S193 50 mg/m2 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. | 0 |
| Hu3S193 100 mg/m2 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. | 0 |
| Hu3S193 200 mg/m2 Hu3S193 was administered weekly for 8 consecutive weeks. The antibody was diluted in physiologic saline containing 5% human serum albumin and infused intravenously at a maximum rate of 100 mg/hour. If patients were stable or responding, they were eligible to receive 8-week maintenance cycles of hu3S193 at 10 mg/m2 starting in week 10 and continuing until progression. | 0 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Disease Progression | 2 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Hu3S193 10 mg/m2 | Total |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 7 Participants |
| Region of Enrollment United States | 7 participants | 7 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 3 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 3 / 7 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 5 / 7 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
Outcome results
Primary
Number of Patients With Dose-limiting Toxicities (DLTs)
Toxicity was graded in accordance with the Common Toxicity Scale developed by NCI (1998) where Grade 1 represents the lowest toxicity grade and Grade 5 death. Dose-limiting toxicity (DLT) was defined as Grade 3 and Grade 4 adverse events which were at least possibly related to study treatment.
Time frame: up to 10 weeks.
Population: All patients who entered the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hu3S193 10 mg/m2 | Number of Patients With Dose-limiting Toxicities (DLTs) | 1 Participants |
| Hu3S193 25 mg/m2 | Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Hu3S193 50 mg/m2 | Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Hu3S193 100 mg/m2 | Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
| Hu3S193 200 mg/m2 | Number of Patients With Dose-limiting Toxicities (DLTs) | 0 Participants |
Secondary
Number of Patients With Tumor Responses
Complete response (CR); disappearance of all measurable disease lasting a minimum of 4 weeks. Partial Response (PR); 50% or greater decrease in the sum of the products of the perpendicular diameters or all measurable lesions, without development of new lesions or increase in size of any lesion, lasting a minimum of 4 weeks. Progressive disease (PD); Appearance of new lesions or increase by 25% or more in size of any measurable lesion. Stable disease (SD); Not meeting criteria for response or progression.
Time frame: 8 weeks
Population: All patients who entered the study and had tumor assessments.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hu3S193 10 mg/m2 | Number of Patients With Tumor Responses | PD | 4 Participants |
| Hu3S193 10 mg/m2 | Number of Patients With Tumor Responses | PR | 0 Participants |
| Hu3S193 10 mg/m2 | Number of Patients With Tumor Responses | SD | 0 Participants |
| Hu3S193 10 mg/m2 | Number of Patients With Tumor Responses | CR | 0 Participants |
| Hu3S193 25 mg/m2 | Number of Patients With Tumor Responses | PR | 0 Participants |
| Hu3S193 25 mg/m2 | Number of Patients With Tumor Responses | CR | 0 Participants |
| Hu3S193 25 mg/m2 | Number of Patients With Tumor Responses | PD | 0 Participants |
| Hu3S193 25 mg/m2 | Number of Patients With Tumor Responses | SD | 0 Participants |
| Hu3S193 50 mg/m2 | Number of Patients With Tumor Responses | CR | 0 Participants |
| Hu3S193 50 mg/m2 | Number of Patients With Tumor Responses | PD | 0 Participants |
| Hu3S193 50 mg/m2 | Number of Patients With Tumor Responses | PR | 0 Participants |
| Hu3S193 50 mg/m2 | Number of Patients With Tumor Responses | SD | 0 Participants |
| Hu3S193 100 mg/m2 | Number of Patients With Tumor Responses | PR | 0 Participants |
| Hu3S193 100 mg/m2 | Number of Patients With Tumor Responses | PD | 0 Participants |
| Hu3S193 100 mg/m2 | Number of Patients With Tumor Responses | SD | 0 Participants |
| Hu3S193 100 mg/m2 | Number of Patients With Tumor Responses | CR | 0 Participants |
| Hu3S193 200 mg/m2 | Number of Patients With Tumor Responses | CR | 0 Participants |
| Hu3S193 200 mg/m2 | Number of Patients With Tumor Responses | PR | 0 Participants |
| Hu3S193 200 mg/m2 | Number of Patients With Tumor Responses | PD | 0 Participants |
| Hu3S193 200 mg/m2 | Number of Patients With Tumor Responses | SD | 0 Participants |