Study of IGF-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R
Breast Cancer - Brain Cancer - Gastrointestinal Cancers - Genitourinary Cancers - Gynecologic Cancers - Head and Neck Cancers - Melanoma - Thoracic Cancers
Conditions: official terms
Gastrointestinal Neoplasms - Head and Neck Neoplasms - Urogenital Neoplasms
Conditions: Keywords
refractory, intolerant, non-hematologic, solid tumors
Study Type
Study Phase
Phase 1
Study Design
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Name: IGF-Methotrexate
Type: Drug
Overall Status
This phase I dose escalation study will evaluate IGF-Methotrexate conjugate (765IGF-MTX) in patients with advanced, previously treated tumors. 765IGF-MTX is administered as an IV infusion over 1 hour on days 1, 8 and 15 of a 28 day cycle. Treatment continues until disease progression, unacceptable toxicity, or patient refusal. Assessment of response will be confirmed with imaging studies performed at the end of cycle 2, and every 2 weeks after.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

1. Diagnosis of advanced malignancy, refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy.

2. Tumor (tissue, bone marrow, or blood) must express IGF-1R, defined as 10% or higher of cells expressing IGF-1R by IHC, or 0.1% or higher for IGF-1R expression by flow cytometry (blood or bone marrow aspirate). Parafin-embedded tissue sections will be stained with antibodies against IGFR-1 according to the manufacturer's recommended protocols. IHC staining will be performed at the Pathology Department of the University of Illinois Cancer Center.

3. Measurable or evaluable disease per RECIST 1.1 criteria for solid tumors & lymphoma.

4. Multiple Myeloma: Confirmed diagnosis of MM with relapsed or refractory disease.

5. Lymphoma: Previously treated, histologically confirmed lymphoma (RECIST 1.1) with exception of lymphoplasmacytic lymphoma

6. Waldenstrom's Macroglobulinemia: Confirmed diagnosis with relapsed/refractory disease, and measurable disease defined as atleast one lesion with a single diameter of greater than 2cm by CT or bone marrow involvement with greater than 10% malignant cells and immunoglobulin (IgM, IgG, IgA) greater than 1000mg/dL.

7. Hematologic malignancies including MDS, leukemia: Confirmed histologic diagnosis with relapsed or refractory disease; measurable disease per RECIST 1.1 criteria is not required.

8. Age ≥ 18 years.

9. ECOG performance status of 0, 1 or 2 (appendix IV).

10. Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; however prior use of methotrexate is not allowed.

Time since prior therapy and the first dose of study drug:

- At least 2 weeks since prior radiation, non cytotoxic small molecule drugs (e.g., tyrosine kinase inhibitors such as erlotinib and hormonal agents such as letrozole), prior major surgery (surgery (defined as a surgery involving a risk to the life of the patient; specifically: an operation upon an organ within the cranium, chest, abdomen, or pelvic cavity), prior systemic FDA approved therapy

- At least 3 weeks since prior antineoplastic therapy

- At least 4 weeks since exposure to monoclonal antibodies (chimeric or fully human)

- At least 6 weeks since prior nitrosureas or mitomycin-C

11. Patient must have recovered from the acute toxic effects (≤ grade 1 CTCAE v4) of previous anti-cancer treatment prior to study enrollment; the only exception is that grade 2 neuropathy is permitted

12. Adequate organ function within 14 days of study registration defined as:

Absolute neutrophil count (ANC) > 1.5 X 109/L Hemoglobin1 > 9 g/dL Platelets1 > 100 X 109/L Total bilirubin < 1.5 x ULN Alkaline Phosphatase, AST and ALT < 3 X ULN (< 5 x ULN is acceptable if liver has tumor involvement) Serum Creatinine ≤ 1.5 x ULN Creatinine Clearance > 60 ml/min [or GFR > 60 ml/min or 24 Hr. Urine Creat Clearance > 50 ml/min] Note: Patient may not have had a transfusion within 7 days of blood draw.

13. Negative urine or serum pregnancy test in females. Male and female patients with reproductive potential must use an approved contraceptive method if appropriate (for example, abstinence, oral contraceptives, implantable hormonal contraceptives, or double barrier methods) during and for 3 months after the last dose of 765IGF-MTX.

14. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.

Exclusion Criteria:

1. Untreated or symptomatic CNS metastases.

2. Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.

3. ≥ Grade 3 peripheral neuropathy within 14 days before enrollment.

4. Systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection.

5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.

6. Pregnant or breastfeeding - methotrexate is Pregnancy Category X - has been reported to cause fetal death and/or congenital abnormalities. Confirmation that the subject is not pregnant must be established by a negative serum Beta-human chorionic gonadotropin (Beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.

7. Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 7% in patients with a prior history of diabetes, 28 days prior to study enrollment.

8. Serious concomitant systemic disorders (e.g., active infection, uncontrolled diabetes) or psychiatric disorders that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.

9. Other severe acute or chronic medical or psychiatric conditions, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.

10. Recent (within 6 months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI).

11. History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.

12. Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.

13. History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months. Note: Subjects with recent DVT who have been treated with therapeutic anticoagulants for at least 6 weeks are eligible.

14. Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug.

15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IGF or methotrexate.
University of Illinois at Chicago
Chicago, Illinois, United States
Status: Recruiting
Contact: Neeta Venepalli, MD - 312-413-2746 -
Start Date
December 2013
Completion Date
January 2017
University of Illinois at Chicago
University of Illinois at Chicago
Record processing date processed this data on July 28, 2015 page