Study of Insulin-like Growth Factor (IGF)-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R

NCT02045368 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: STM-022013-0655
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

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 +/- 7 days, and every 2 weeks thereafter.

Conditions

Breast Cancer; Brain Cancer; Gastrointestinal Cancers; Genitourinary Cancers; Gynecologic Cancers; Head and Neck Cancers; Melanoma; Thoracic Cancers

Keywords

refractory; intolerant; solid tumors

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  The primary objective is to determine the maximum tolerated dose (MTD) of 765IGF-MTX by evaluation of toxicity for the treatment of advanced, previously treated malignancies that express IGF-1R.

  Up to 30 days after final dose.

Secondary Outcomes (2)

• Adverse Effects

  Up to 30 days after last dose study drug.

• Disease Response based on RECIST Criteria

  Up to 8 weeks after last dose study drug.

Study Arms (1)

Subject Treatment with IGF-Methotrexate conjugate

EXPERIMENTAL

IV infusion at the assigned dose administered on days 1, 8, and 15 of a 28 day (4 week) cycle.

Drug: IGF-Methotrexate conjugate

Interventions

IGF-Methotrexate conjugate DRUG

IV infusion at the assigned dose administered on days 1, 8, and 15 of a 28 day (4 week) cycle. Up to 7 dose levels will be tested, starting with 0.05 microequivalents per kg and up to 2.5 microequivalents per kg.

Also known as: 765IGF-MTX

Subject Treatment with IGF-Methotrexate conjugate

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of advanced malignancy, refractory to or intolerant to standard therapy and is no longer likely to respond to such therapy.
• Tumor (tissue, bone marrow, or blood) must express IGF-1R, defined as 10% or higher of cells expressing IGF-1R by immuno-histochemistry (IHC), or 0.1% or higher for IGF-1R expression by flow cytometry (blood or bone marrow aspirate).
• Paraffin-embedded tissue sections will be stained with antibodies against insulin-like growth factor receptor 1 (IGFR-1) according to the manufacturer's recommended protocols. IHC staining and flow cytometry will be performed at the Pathology Department of the University of Illinois Cancer Center.
• Measurable or evaluable disease per RECIST 1.1 criteria for solid tumors and lymphoma as defined in the protocol. For other hematologic malignancies, see below (measurable disease per RECIST 1.1 criteria not necessary).
• Multiple Myeloma: Confirmed diagnosis of multiple myeloma as defined in the protocol with relapsed or refractory disease, and measurable disease defined as one of below:
• Serum monoclonal protein \> 500mg/dL by serum protein electrophoresis (SPEP)
• Urine monoclonal protein \> 200mg/24 hours by urine protein electrophoresis (UPEP)
• Measurable free light chain by free light chain assay \> 10mg/dL with abnormal kappa to lambda light chain ratio
• Measurable bone disease by \> 1 bone lesion which is \> 20 mm on conventional techniques or \> 10 mm with spiral CT (for lytic lesions)
• Monoclonal bone marrow plasmacytosis \> 30%
• Lymphoma: Previously treated, histologically confirmed lymphoma with measurable disease via RECIST 1.1, with the exception of lymphoplasmacytic lymphoma, which can be diagnosed based on morphologic evidence in the bone marrow plus the appropriate paraprotein.
• Waldenstrom's Macroglobulinemia: Confirmed diagnosis with relapsed or refractory disease, and measurable disease defined as at least 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.
• Hematologic malignancies including myelodysplastic syndrome(MDS), leukemia: Confirmed histologic diagnosis with relapsed or refractory disease; measurable disease per RECIST 1.1 criteria is not required.
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

You may not qualify if:

• Untreated central nervous system (CNS) metastases
• Radiation therapy to more than 25% of the bone marrow. Whole pelvic radiation is considered to be over 25%.
• ≥ Grade 3 peripheral neuropathy within 14 days before enrollment.
• Systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection.
• 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.
• 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.
• Uncontrolled diabetes mellitus defined as a Hemoglobin A1C≥ 7% in patients with a prior history of diabetes, 28 days prior to study enrollment.
• 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.
• 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.
• Recent (within 6 months) arterial thromboembolic events, including transient ischemic attack (TIA), cerebrovascular accident (CVA), unstable angina, or myocardial infarction (MI).
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment.
• Abnormalities on 12-lead electrocardiogram (ECG) considered by the investigator to be clinical significant.
• 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.
• Presence of any non-healing wound, fracture, or ulcer within 28 days prior to the first dose of study drug.
• Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to IGF or methotrexate

Sponsors & Collaborators

• IGF Oncology, LLC: lead

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Brain Neoplasms; Gastrointestinal Neoplasms; Urogenital Neoplasms; Head and Neck Neoplasms; Melanoma

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms

Study Officials

• Neeta Venepalli, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2014
• First Posted: January 24, 2014
• Study Start: January 28, 2014
• Primary Completion: September 30, 2016
• Study Completion: September 30, 2016
• Last Updated: August 22, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)