131-I-TM-601 Study in Adults With Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase I Imaging and Safety Study of Intravenous 131-I-TM-601 Labeled Chlorotoxin in Patients With Recurrent or Refractory Somatic and/or Cerebral Metastatic Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00379132
• Other study ID #: TM601-003
• Status: Completed
• Phase: Phase 1
• First received: September 18, 2006
• Last updated: March 30, 2009
• Start date: August 2006
• Est. completion date: August 2008

Study information

• Verified date: March 2009
• Source: TransMolecular
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the ability of intravenously (IV)administered 131-I-labeled TM-601 (chlorotoxin) to provide tumor-specific localization(via radiographic imaging) in patients with recurrent or refractory primary solid tumors with evidence of metastatic involvement. (Refractory tumors are non-responsive to standard treatment.) The safety and tolerability of IV administered 131-I-TM-601 in this patient population will be evaluated as part of this study.

Description:

This is a multi-center, open label, non-randomized, sequential, within-patient dose-escalation study in patients with recurrent or refractory primary solid tumors with metastatic involvement (including brain metastases). Patients will be administered 1 to 3 (Test Doses A, B and Dose C) escalating doses of 131-I-TM-601 by intravenous (IV) administration, with dosimetry (imaging-based evaluation of the dose reaching the target sites) conducted prior to and following administration of each dose. Whole body dosimetry on critical structures including, but not limited to, bone marrow, bladder, brain, liver, and thyroid will be determined. The preliminary results from Test Dose Levels (A and/or B) for each patient will be analyzed prior to treating patients with Dose C.

Patients will be followed until 28 days following the final dose, with a complete clinical assessment and imaging evaluations at the final follow-up visit.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: August 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed recurrent or refractory primary solid tumor malignancy. Primary tumor cell type is one of the following: breast, non-small cell lung, melanoma, colorectal, prostatic adenocarcinoma (hormone refractory) or glioma. Note: Patients with a primary solid tumor cell type not listed above, meeting all other selection criteria may be considered eligible, on a case by case basis

• Demonstration of distant metastatic involvement as seen with standard clinical non-invasive imaging techniques (CT/MRI) or on biopsy. Note: on a case-by-case basis, patients with a locally recurrent, unresectable (inoperable) tumor may be considered for inclusion

• Refractory to standard curative treatment

• At least 18 years of age

• Baseline Karnofsky Performance Status (KPS) of 60-100%

• Life expectancy, based on investigator judgement, of greater than 3 months

• Adequate organ and marrow function (as defined in protocol)

• Women of child-bearing potential must have a negative pregnancy test, refrain from nursing, and must agree to use appropriate contraception for the duration of the trial

Exclusion Criteria:

• Prior cytotoxic chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study

• Patients who have not sufficiently recovered from adverse events due to previously administered agents

• Concurrent treatment with investigational or commercial agents or therapies administered with the intent to treat the patient's malignancy, including chemotherapy, immunotherapy, biological response modifiers, or palliative radiotherapy. Possible exceptions (at the discretion of the investigator) are for hormonal therapy for breast and prostate cancer, hematologic, analgesic, biphosphonate, and any other form of supportive therapy.

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 131-I-labeled chlorotoxin (e.g. iodine or iodine-containing drugs)

• Patients with uncontrolled intercurrent illness.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Breast Cancer
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Glioma
• Melanoma
• Non-Small Cell Lung Cancer
• Pancreatic Cancer
• Pancreatic Neoplasms
• Primary Solid Tumors
• Prostate Adenocarcinoma
• Prostatic Neoplasms

Intervention

Drug:
• 131-I-TM-601 (chlorotoxin)
Patients will be administered 1 - 3 (Test Doses A, B, and Dose C) escalating doses of 131I-TM601 by intravenous (IV) administration. Each dose will be administered as a single administration, scheduled at one-week intervals. Test Dose A - 10 mCi (+/- 20%)/0.2 mg TM601 (131I-TM601) Test Dose B - 20 mCi (+/- 20%)/0.4 mg TM601 (131I-TM601) Dose C - 30 mCi (+/- 10%)/0.6 mg TM601 (131I-TM601)

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Tufts - New England Medical Center	Boston	Massachusetts
United States	Northwestern University, The Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Lacks Cancer Center at St. Mary's Health Care	Grand Rapids	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
TransMolecular

Country where clinical trial is conducted

United States, 

References & Publications (4)

Hockaday DC, Shen S, Fiveash J, Raubitschek A, Colcher D, Liu A, Alvarez V, Mamelak AN. Imaging glioma extent with 131I-TM-601. J Nucl Med. 2005 Apr;46(4):580-6. — View Citation

Lyons SA, O'Neal J, Sontheimer H. Chlorotoxin, a scorpion-derived peptide, specifically binds to gliomas and tumors of neuroectodermal origin. Glia. 2002 Aug;39(2):162-73. — View Citation

Mamelak AN, Jacoby DB. Targeted delivery of antitumoral therapy to glioma and other malignancies with synthetic chlorotoxin (TM-601). Expert Opin Drug Deliv. 2007 Mar;4(2):175-86. Review. — View Citation

Mamelak AN, Rosenfeld S, Bucholz R, Raubitschek A, Nabors LB, Fiveash JB, Shen S, Khazaeli MB, Colcher D, Liu A, Osman M, Guthrie B, Schade-Bijur S, Hablitz DM, Alvarez VL, Gonda MA. Phase I single-dose study of intracavitary-administered iodine-131-TM-601 in adults with recurrent high-grade glioma. J Clin Oncol. 2006 Aug 1;24(22):3644-50. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate whether intravenous (IV) 131-I-TM-601 provides tumor-specific localization in patients with recurrent or refractory metastatic (including brain metastases) solid tumors		between 1 - 72 hours post study dose	No
Primary	To determine the distribution and dosimetry of intravenously administered 131-I-TM-601		between 1 - 72 hours post study dose	Yes
Primary	To determine the safety and tolerability of IV administered 131-I-TM-601.		within 28 days of last study drug administration	Yes