Dose Finding Study of Once or Twice Weekly IMMU-130 in Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This is a Phase I/II, open-label study of IMMU-130 administered in 21-day treatment cycles, once or twice weekly for 2 consecutive weeks followed by one week of rest to patients with metastatic colorectal cancer who have been previously treated with at least one prior irinotecan-containing regimen. The study is being done to evaluate whether the study drug is safe and tolerable at different dose levels with these dosing schedules and to obtain preliminary information on its efficacy.

Official Title
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A Phase I/II Study of Once or Twice Weekly IMMU-130 (hMN-14-SN38, Antibody-Drug Conjugate) in Patients With Colorectal Cancer.

Conditions
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Metastatic Colorectal Cancer, Colon Cancer, Rectal Cancer

Intervention / Treatment
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* Drug: IMMU-130


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients, ≥ 18 years of age, able to understand and give written informed consent. Histologically or cytologically confirmed colorectal adenocarcinoma. Stage IV (metastatic) disease. Previously treated with at least one prior irinotecan-containing regimen for colorectal cancer. Adequate performance status (ECOG 0 or 1). (Appendix 1) Expected survival > 6 months. CEA plasma levels > 5 ng/mL. Measurable disease by CT or MRI. At least 4 weeks beyond treatment (chemotherapy, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities. At least 2 weeks beyond corticosteroids. Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, ANC > 1,500 per mm3, platelets > 100,000 per mm3). Adequate renal and hepatic function (creatinine ≤ 1.5 x IULN, bilirubin ≤ IULN, AST and ALT ≤ 3.0 x IULN or 5 x IULN if know liver metastases). Otherwise, all toxicity at study entry ≤ Grade 1 by NCI CTC v4.0. Exclusion Criteria: Women who are pregnant or lactating. Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period. Patients with Gilbert's disease or known CNS metastatic disease. Patients with CEA plasma levels > 1000 ng/mL are excluded during dose escalation, but may be included after the MTD is determined. Presence of bulky disease (defined as any single mass > 10 cm in its greatest dimension). Patients with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction. Patients with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while patients with other prior malignancies must have had at least a 3-year disease-free interval. Patients known to be HIV positive, hepatitis B positive, or hepatitis C positive. Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy. Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months. Infection requiring intravenous antibiotic use within 1 week. Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMMU-130<br>All patients receive IMMU-130 administered in 21-day treatment cycles consisting of once or twice weekly for 2 consecutive weeks followed by a 1-week rest period. Treatment can be continued in the absence of unacceptable toxicity for a period of up to 8 cycles until the first documentation of Progressive Disease by CT (physician discretion), but must terminate study treatment upon the second documentation of Progressive Disease. | Drug: IMMU-130<br>* This is a Phase I/II, open-label study of IMMU-130 administered in 21-day treatment cycles, once or twice weekly for 2 consecutive weeks followed by one week of rest to patients with metastatic colorectal cancer who have been previously treated with at least one prior irinotecan-containing regimen.<br>* Other names: Antibody-Drug Conjugate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety and tolerability of IMMU-130 |  | Every 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Obtain information on efficacy | Efficacy will be evaluated from CT scans using RECIST criteria | During treatment and the changes at 4, 8 and 12 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic colorectal cancer, colon cancer, rectal cancer, previously treated