Clinical trial NCT00379132: 131-I-TM-601 Study in Adults With Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Non-Small Cell Lung Cancer
Melanoma
Colorectal Cancer
Pancreatic Cancer
Prostate Adenocarcinoma
Glioma
Primary Solid Tumors
Keywords: Glioma
prostatic
breast
non-small cell lung
melanoma
colorectal
pancreatic
Lead sponsor: TransMolecular
Sponsor class: INDUSTRY
First posted: 2006-09-21
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: between 1 - 72 hours post study dose
measure: To determine the distribution and dosimetry of intravenously administered 131-I-TM-601
timeFrame: between 1 - 72 hours post study dose
measure: To determine the safety and tolerability of IV administered 131-I-TM-601.
timeFrame: within 28 days of last study drug administration
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Chicago
country: United States
facility: Northwestern University, The Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Boston
country: United States
facility: Tufts - New England Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at St. Mary's Health Care
state: Michigan
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
Study officials:
affiliation: University of Alabama at Birmingham
name: John Fiveash, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Jeffrey Raizer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Mary Crowley Medical Research Center
name: Neil Senzer, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lacks Cancer Center at St. Mary's Health Care
name: Thomas Gribbins, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tufts Medical Center
name: Jay-Jiguang Zhu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Chicago
name: Steven Chmura, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1517/17425247.4.2.175.
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. doi: 10.1200/JCO.2005.05.4569.
citation: 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.
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. doi: 10.1002/glia.10083.