Study of TF2 Carcinoembryonic Antigen (CEA) Antibody in Patients With Metastatic Colorectal Cancer

This study has been terminated.
(A new study is being designed. No patients were enrolled.)
Sponsor:
Collaborator:
Information provided by:
Immunomedics, Inc.
ClinicalTrials.gov Identifier:
NCT01273402
First received: January 5, 2011
Last updated: September 24, 2012
Last verified: September 2012
  Purpose

This study is being done to select an appropriate TF2 bsMAb dose suitable for pretargeting the 111In/90Y-labeled hapten-peptide (IMP-288). Eligible patients will receive a fixed dose of 90Y-IMP-288 4 days after the TF2 antibody injection. Two different dose levels of TF2 will be studied in the first part.

Once an appropriate TF2 dose is selected based on information learned from the first 2 dose levels, patients will be enrolled onto several different increasing dose levels of 90Y-IMP-288.


Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: TF2/IMP288
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pretargeted Radioimmunotherapy of Colorectal Cancer: A Phase I Study to Determine Dose-limiting Toxicity and Maximum Tolerated Dose of an Anti-CEACAM5 bsMAb-pretargeted 90Y-hapten-peptide

Resource links provided by NLM:


Further study details as provided by Immunomedics, Inc.:

Primary Outcome Measures:
  • Safety [ Time Frame: Safety will be measured routinely during the 3 weeks of administration and afterwards during follow-up for up to 5 years ] [ Designated as safety issue: Yes ]
    Safety will be assessed by determing the number of participants with Adverse Events as a Measure of Safety and Tolerability.


Secondary Outcome Measures:
  • Efficacy will be evaluating using CT scans and possibly PET imaging. [ Time Frame: Efficacy will be measured at 4 and 8 weeks after treatment and every 3 months for up to 2 years. ] [ Designated as safety issue: No ]
    CT scans will primarily be used to assess tumor response and to assess the change in tumor size from baseline for up to 2 years.


Estimated Enrollment: 30
Study Start Date: February 2011
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TF2 and IMP288
TF2 will be administered at least 4 days before the radiolabeled IMP-288.
Drug: TF2/IMP288
TF2 is administered 4 days prior to radiolabeled IMP288. Each are given weekly for 2 weeks.
Other Names:
  • TF2
  • IMP288
  • bi-specific antibodies
  • pre-targeted antibodies

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female patients, >18 years of age.
  • documented histologic or cytologic diagnosis of metastatic (Stage IV) colorectal cancer.
  • must have at least one confirmed and measurable tumor lesion (a confirmed tumor site is one in which either biopsy-proven evidence of disease or progressive growth has been radiographically observed).
  • Patients must have failed standard therapy or for whom no standard therapy exists.
  • Patients must have a Karnofsky performance status of ≥ 70% (or equivalent ECOG 0-1) and an expected survival of ≥ 3 months.
  • Patients who previously received a chimeric, CDR-grafted (humanized), or human IgG will be eligible provided pre-study evaluations demonstrate no significant anti-antibody reactivity with TF2.
  • Hematologic parameters: WBC counts must be ≥ 3000/mm3, granulocytes

    • 1500/mm3, and platelets ≥ 100,000/m3.
  • Non-hematologic parameters: Patients without liver metastases must have bilirubin ≤ 1.5 institutional upper limit of normal (IULN), whereas bilirubin in patients with known liver metastases must be <2.5-times the IULN. AST/ALT must not be >2.5 times IULN.
  • At least 2 weeks beyond corticosteroids, except low doses (i.e., 20 mg/day of prednisone or equivalent) to treat nausea or other illness such as rheumatoid arthritis.
  • Patients able to understand and give written informed consent. Informed consent must be obtained prior to baseline studies for enrollment purposes.

Exclusion Criteria:

  • Women who are pregnant or lactating. Women of childbearing potential and fertile men will be informed as to the potential risk of procreation while participating in this trial and will be advised that they must use effective contraception during and for a period of 3 months.
  • Patients with plasma CEA >1000 ng/mL or lesions exceeding 10 cm in diameter.
  • Patients with severe anorexia or other gastrointestinal-related symptomatology (e.g., nausea, vomiting).
  • Patients with known HIV or hepatitis B or C.
  • Patients with an active second primary malignancy at the time of study entry, with the exception of carcinoma in situ of the cervix.
  • Patients with known metastatic disease to the central nervous system.
  • Patients with evidence of bone marrow metastases. Screening only required for patients with suspicion of metastases. Patients with ≥ 25% bone marrow involvement are excluded.
  • Patients who are, in the opinion of the investigator, unable to comply with the protocol requirements.
  • Institutionalized subjects (e.g., prisons, psychiatric facilities).
  • Known history of active coronary artery disease, unstable angina, myocardial infarction, or congestive heart failure present within 6 months or cardiac arrhythmia requiring anti-arrhythmia therapy.
  • Known autoimmune disease or presence of autoimmune phenomena (except rheumatoid arthritis requiring only low dose maintenance corticosteroids); or infection requiring intravenous antibiotic use within 1 week.
  • Known history of active COPD, or other moderate-to-severe respiratory illness present within 6 months.
  • Patients who are diabetic and/or have high blood pressure are at a higher risk for developing late-stage renal failure. While these patients will not be specifically excluded, physician-investigators must carefully discuss the associated late risks to these patients.
  • Patients must be at least 4 weeks beyond prior chemotherapy, surgery, radiotherapy to an index lesion, or experimental therapy (i.e., drugs, biologicals, procedures) and meet all eligibility criteria.
  • Patients who received a treatment containing a nitrosourea compound will not be enrolled for at least 6 weeks after the end of that treatment.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01273402

Locations
United States, District of Columbia
Georgetown University Medical Center
Washington, District of Columbia, United States, 20057
Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Principal Investigator: Robert Sharkey, PhD Garden State Cancer Center/Center for Molecular Medicine and Immunology
  More Information

Publications:

Responsible Party: Robert Sharkey, PhD, Garden State Cancer Center/Center for Molecular Medicine and Immunology
ClinicalTrials.gov Identifier: NCT01273402     History of Changes
Other Study ID Numbers: C-072-09 (NCI 5R01CA107088-04), 5R01CA107088-04
Study First Received: January 5, 2011
Last Updated: September 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Immunomedics, Inc.:
colorectal cancer
TF2 (Recombinant, humanized Tri-Fab bsMAb composed of 2 humanized MN-14 anti-CEA Fab x and one 679 anti-HSG Fab)
IMP288 (DOTA-di-HSG hapten-peptide for 111In/90Y labeling)

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Immunoglobulins
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014