Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors

NCT01999738 | Completed Phase 1 FDA Drug

• 1 other identifier: EC1456-01
• Study Type: interventional
• Target: 93
• Locations: 1 country
• Sites: 16

Brief Summary

Phase 1A/B, multicenter, open-label, non-randomized, dose-escalation oncology study to evaluate the administration of EC1456 in advanced solid tumors. In part A, EC1456 will be dose escalated on 4 concurrently enrolling schedules. FR-positive expression on a 99mTc-etarfolatide scan is not required for inclusion in Part A. Part B of the study will confirm the maximum tolerated dose (MTD) and the recommended Phase 2 (RP2) dose of EC1456, and evaluate the efficacy of EC1456 in NSCLC all subtype patient populations with FR-positive cancer in up to three schedules (i.e., twice weekly, once weekly, and four times weekly). FR-positive expression on a 99mTc-etarfolatide scan is required for inclusion in Part B. Minimum length of patient participation is anticipated to be 10 weeks (two 3-week cycles followed by a 30 day follow-up period).

Conditions

Solid Tumors; Non Small Cell Lung Carcinoma

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2) - Part A

  Part A - To dose escalate EC1456 dose until maximum tolerated dose (MTD) and recommended Phase 2 (RP2) dose for multiple schedules is reached. -All patients who receive at least one dose of EC1456 will be evaluated for safety. All AEs and SAEs will be graded as per CTCAE V4.0. For each dose level, summaries of dose adjustments, adverse event rates, laboratory changes, cumulative toxicity, and dose limiting toxicity (DLT) will be analyzed. Summaries of CTCAE grades will be analyzed at each dose level and each cycle.

  18-24 months

• Efficacy Analysis - Part B

  Part B - Response to study therapy will be calculated per RECIST v1.1 criteria for all patients treated with at least one dose of EC1456

  18-24 months

Study Arms (7)

Part A - MTD (Treatment 1)

EXPERIMENTAL

Treatment 1 is BIW on Days 1, 4, 8, and 11 of a 3-week schedule (BIW). Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Part A - MTD (Treatment 2)

EXPERIMENTAL

Treatment 2 is EC1456 QW on Days 1 and 8 of a 3-week schedule (QW). Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Part A - MTD (Treatment 3)

EXPERIMENTAL

Treatment 3 is EC1456 QW on Days 1, 8, and 15 of a 3-week schedule (CWD). Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Part A - MTD (Treatment 4)

EXPERIMENTAL

Treatment 4 is EC1456 QIW on Days 1, 2, 3, 4, 8, 9, 10, and 11 of a 3-week schedule (QIW). Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Part B - Efficacy (Treatment 5)

EXPERIMENTAL

Treatment 5 is EC1456 BIW. Once a dose is determined in Part A, Part B will begin with 3-6 subjects who will receive consecutive day dosing on Days 1, 2, 8, and 9 of a 3-week schedule. If this is not tolerated, the BIW cohort will continue with dosing on Days 1, 4, 8, and 11 of a 3-week schedule. Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Part B - Efficacy (Treatment 6)

EXPERIMENTAL

Treatment 6 is EC1456 QW on Days 1 and 8 of a 3-week schedule or CWD on Days 1, 8 and 15 of a 3-week schedule. Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Part B - Efficacy (Treatment 7)

EXPERIMENTAL

Treatment 7 is EC1456 QIW on Days 1, 2, 3, 4, 8, 9, 10, and 11 of a 3-week schedule for at least two cycles. If the patient is eligible to continue treatment (based upon treatment response and tolerability), he/she may opt to continue on the QIW schedule or change to the Treatment 6 regimen schedule (once its MTD and schedule have been determined). Intervention: EC1456 and EC20

Drug: EC1456 and EC20

Interventions

EC1456 and EC20 DRUG

EC1456 is small molecule drug conjugate of folic acid and tubulysin B hydrazide (TubBH) that specifically binds to the membrane-bound FR and gains entry into the cell via endocytosis. EC20 is Etarfolatide, a conjugate of folic acid and a tripeptide moiety that can efficiently chelate the radioisotope 99mTechnetium (99mTc). When etarfolatide is labeled with 99mTc, the product (99mTc-etarfolatide) is able to quantify FR expressing tissues with SPECT imaging.

Also known as: Folic acid and tubulysin B hydrazide and etarfolatide

Part A - MTD (Treatment 1); Part A - MTD (Treatment 2); Part A - MTD (Treatment 3); Part A - MTD (Treatment 4); Part B - Efficacy (Treatment 5); Part B - Efficacy (Treatment 6); Part B - Efficacy (Treatment 7)

Eligibility Criteria

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

You may qualify if:

• Patients enrolled in Part A must receive the 99mTc- etarfolatide scan but they do not need to have FR-positive target lesions.
• Parts A and B:
• To qualify for enrollment, the following criteria must be met:
• Patient must have the ability to understand and sign an approved informed consent form (ICF).
• Patient must be ≥ 18 years of age.
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Patient must have a life expectancy of \> 3 months.
• Patient must have at least one measurable lesion per RECIST v1.1 Criteria as assessed on baseline radiologic evaluation obtained no more than 28 days prior to beginning study therapy.
• Patients with central nervous system (CNS) metastases that are symptomatic must have received therapy (e.g., surgery, XRT, gamma knife, etc.) and be neurologically stable and off of steroids. The patient should be off steroids at least 14 days before registration. Patients with asymptomatic CNS metastatic disease without associated edema, shift, and a requirement for steroids or anti-seizure medications may be eligible after discussion with the sponsor medical monitor.
• Patients must have formalin fixed tissue (biopsy or FNA) available.
• Patient must have recovered (to baseline/stabilization) from prior chemo or radio therapy and associated acute toxicities must have resolved to a NCI CTCAE V4 Grade 1 or less, with the exception of alopecia.
• Patients treated with prior radiation therapy may be eligible if:
• Radiotherapy was completed at least 2 weeks before first dose of EC1456 and
• Patient has recovered from acute radiation toxicity.
• Patients must have adequate organ function:

You may not qualify if:

• Parts A and B:
• The presence of any of the following will exclude patients from the study:
• Systemic anti-cancer treatment, except hormonal treatment, within 28 days prior to EC1456 administration unless there are no remaining or ongoing uncontrolled toxicities. Please contact the medical monitor to discuss requests for less than 28 day washout period.
• Known hypersensitivity to the components of the study therapy or its analogs.
• Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases.
• Malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, carcinoma in situ of the cervix, or low-grade (Gleason score ≤ 6) localized prostate cancer, ductal carcinoma in situ (DCIS), and patients with prior history of malignancy who have been disease free for more than 3 years are eligible.
• Serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension.
• Patients considered at risk for life-threatening QTc prolongation (i.e., personal or family history of Long QT syndrome, presence of implantable pacemaker or implantable cardioverter defibrillator, etc.).
• Use of the following medications within 6 months prior to EC1456 administration: amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine, or sotalol.
• Need for concurrent anti-folate therapy such as methotrexate for rheumatoid arthritis.
• Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.
• Pregnant or lactating women.
• Active uncontrolled infections.
• Known active Hepatitis B or C infection.
• Unable or unwilling to have a pretreatment scan performed with 99mTc-etarfolatide for any reason (such as claustrophobia, an inability to lie supine on an imaging table because of pain or cardiopulmonary disease, etc.).

Sponsors & Collaborators

• Endocyte: lead

Study Sites (16)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Honor Health

Scottsdale, Arizona, 85258, United States

Location

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Northwestern University Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

IU Health Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Horizon BioAdvance

Lafayette, Indiana, 47905, United States

Location

University of Maryland-Greenebaum Cancer Center

Baltimore, Maryland, 21201-1595, United States

Location

Henry Ford Hospital - Josephine Ford Cancer Center

Detroit, Michigan, 48202, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

University Hospitals Case Medical Center - Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Westchase Clinical Associates

Houston, Texas, 77042, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77230, United States

Location

University of Vermont Cancer Center

Burlington, Vermont, 05401, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Folic Acid

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Alison Armour, MD

  Endocyte

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2013
• First Posted: December 3, 2013
• Study Start: October 1, 2013
• Primary Completion: December 31, 2017
• Study Completion: April 26, 2018
• Last Updated: February 7, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)