Solid Tumors Clinical Trial
Official title:
A Phase I A/B Study of the Folic Acid-Tubulysin Conjugate EC1456 In Patients With Advanced Solid Tumors
Verified date | February 2019 |
Source | Endocyte |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 93 |
Est. completion date | April 26, 2018 |
Est. primary completion date | December 31, 2017 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: 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: 1. Patient must have the ability to understand and sign an approved informed consent form (ICF). 2. Patient must be = 18 years of age. 3. Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4. Patient must have a life expectancy of > 3 months. 5. 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. 6. 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. 7. Patients must have formalin fixed tissue (biopsy or FNA) available. 8. 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. 9. Patients treated with prior radiation therapy may be eligible if: 1. Radiotherapy was completed at least 2 weeks before first dose of EC1456 and 2. Patient has recovered from acute radiation toxicity. 10. Patients must have adequate organ function: 1. Bone marrow reserve: Absolute neutrophil count (ANC) = 1.5 x 109/L; Platelets = 100 x 109/L; Hemoglobin = 9 g/dL. 2. Cardiac: i. QTcFridericia (QTcF) < 450 msec on at least 2 of 3 screening ECG's. On site determination of QTcF may be used for screening purposes. ii. Left ventricular ejection fraction (LVEF) equal to or greater than the institutional lower limit of normal. LVEF must be evaluated within 28 days prior to C1D1. iii. Cardiac Troponin I or T within normal limit. (whichever troponin is done for screening will need to be done throughout the rest of the study). c. Hepatic: Total bilirubin = 1.5 x the upper limit of normal (ULN); Alanine aminotransferase (ALT), aspartate aminotransferase (AST) = 3.0 x ULN OR = 5.0 x ULN for patients with liver metastases. d. Renal: Serum creatinine = 1.5 x ULN or for patients with serum creatinine > 1.5 ULN, creatinine clearance = 50 mL/min. Patients of childbearing potential: 11. All women of childbearing potential MUST have a negative urine or serum pregnancy test within 1 week prior to the 99mTc-etarfolatide imaging procedure and within 1 week prior to treatment with EC1456. 12. Women of child bearing potential must practice an effective method of birth control (i.e., oral, transdermal or injectable contraceptives, intrauterine device [IUD], or double-barrier contraception, such as diaphragm and spermicidal jelly) for the duration of their participation in the trial through 90 days following the last dose of EC1456. 13. Male patients who are sexually active must practice an effective method of birth control (e.g., condom and spermicidal jelly) for the duration of their participation in the trial through 90 days following the last dose of EC1456. Patient and Disease Specific Inclusion Criteria: Part A EC1456 dose escalation cohorts (Treatments 1, 2, 3, and 4): 14. Patients must have pathologically confirmed metastatic or locally advanced solid cancer (preferably TNBC, NSCLC, ovarian, or endometrial cancers due to frequent high FR expression in these cancers) that has failed to respond to standard therapy, is not amenable to standard therapy, or for which standard therapy does not exist. 15. TNBC and ovarian patients must agree to submit results of BRCA 1/2 status (i.e., deleterious mutation present, mutation of unknown significance, no mutation detected) if known. BRCA testing is not required for study inclusion. 16. Patients must have received = 4 prior lines of systemic anti-cancer therapy (including but not limited to cytotoxic agents, targeted inhibitors, and monoclonal antibodies). Hormonal therapies are not included toward this criterion. 17. Patients must undergo a 99mTc-etarfolatide SPECT imaging procedure in compliance with the Investigator's Imaging Operations Manual (IIOM). FR expression on 99mTc -etarfolatide SPECT is not required for inclusion in Treatments 1, 2, 3, and 4. (Patients who underwent a 99mTc-etarfolatide SPECT/CT imaging procedure as a subject on Endocyte study EC20.12 will not be required to have a repeat scan for participation in study EC1456-01 if the scan was obtained within 4 weeks of cycle 1 day 1 of EC1456 administration and has been deemed acceptable by Endocyte Imaging.) Part B Only: Patient and Disease Specific Inclusion Criteria: Part B Patients with FR-positive NSCLC (all subtypes): (Treatments 5, 6, and 7) 18. Patients with NSCLC (all subtypes) must have received one prior platinum based therapy for advanced or metastatic disease. No additional cytotoxic therapy for advanced or metastatic disease is allowed. Any number of prior targeted therapies (e.g., inhibitors of ALK, EGFR, and PD-1 or PD-L1) are allowed. Patients with known relevant genomic tumor aberrations (i.e., EGFR, ALK, ROS-1, etc) must have received and progressed on approved therapy for these aberrations. This information must be documented prior to study entry. 19. Patients must undergo a 99mTc-etarfolatide SPECT imaging procedure in compliance with the Investigator's Imaging Operations Manual (IIOM) and be FR-positive. Exclusion Criteria: Parts A and B: The presence of any of the following will exclude patients from the study: 1. 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. 2. Known hypersensitivity to the components of the study therapy or its analogs. 3. Carcinomatous meningitis and/or symptomatic central nervous system (CNS) metastases. 4. 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. 5. Serious cardiac illness or medical conditions such as unstable angina, pulmonary embolism, or uncontrolled hypertension. 6. 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.). 7. Use of the following medications within 6 months prior to EC1456 administration: amiodarone, disopyramide, dofetilide, dronedarone, flecanamide, ibutilide, quinidine, or sotalol. 8. Need for concurrent anti-folate therapy such as methotrexate for rheumatoid arthritis. 9. Other concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy. 10. Pregnant or lactating women. 11. Active uncontrolled infections. 12. Known active Hepatitis B or C infection. 13. 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.). |
Country | Name | City | State |
---|---|---|---|
United States | University of Maryland-Greenebaum Cancer Center | Baltimore | Maryland |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | University of Vermont Cancer Center | Burlington | Vermont |
United States | Northwestern University Robert H. Lurie Comprehensive Cancer Center | Chicago | Illinois |
United States | University Hospitals Case Medical Center - Seidman Cancer Center | Cleveland | Ohio |
United States | Henry Ford Hospital - Josephine Ford Cancer Center | Detroit | Michigan |
United States | City of Hope | Duarte | California |
United States | IU Health Goshen Center for Cancer Care | Goshen | Indiana |
United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | Westchase Clinical Associates | Houston | Texas |
United States | Indiana University Cancer Center | Indianapolis | Indiana |
United States | Horizon BioAdvance | Lafayette | Indiana |
United States | Weill Cornell Medical College | New York | New York |
United States | Mayo Clinic | Phoenix | Arizona |
United States | Honor Health | Scottsdale | Arizona |
United States | University of Arizona Cancer Center | Tucson | Arizona |
Lead Sponsor | Collaborator |
---|---|
Endocyte |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT00750841 -
Study of the Effect of Rifampicin on the Pharmacokinetics (PK) of Multiple Doses of Cediranib in Patients With Solid Tumours
|
Phase 1 | |
Withdrawn |
NCT05419817 -
Pembrolizumab With Sitravatinib in Recurrent Endometrial Cancer and Other Solid Tumors With Deficient Mismatch Repair System
|
Phase 2 | |
Completed |
NCT02828930 -
A Study to Determine the Excretion Balance, Pharmacokinetics, Metabolism and Absolute Oral Bioavailability of a Single Oral Dose of [14C]-Labeled Idasanutlin and an Intravenous Tracer Dose of [13C]-Labeled Idasanutlin in a Single Cohort of Participants With Solid Tumors (Malignancies)
|
Phase 1 | |
Completed |
NCT01197170 -
Hormone Receptor Positive Disease Across Solid Tumor Types: A Phase I Study of Single-Agent Hormone Blockade and Combination Approaches With Targeted Agents to Provide Synergy and Overcome Resistance
|
Phase 1 | |
Completed |
NCT03258515 -
A Study to Investigate the Effect of Single Dose of AZD6094 (600 mg) on Cardiac Repolarization in Healthy Volunteers
|
Phase 1 | |
Terminated |
NCT03225105 -
M3541 in Combination With Radiotherapy in Solid Tumors
|
Phase 1 | |
Completed |
NCT01497925 -
Ph 1 Trial of ADI-PEG 20 Plus Docetaxel in Solid Tumors With Emphasis on Prostate Cancer and Non-Small Cell Lung Cancer
|
Phase 1 | |
Completed |
NCT01878890 -
Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
|
Phase 1 | |
Active, not recruiting |
NCT05059522 -
Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing
|
Phase 3 | |
Active, not recruiting |
NCT03634982 -
Dose Escalation of RMC-4630 Monotherapy in Relapsed/Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT04685226 -
A Phase I/II Clinical Trial of ICP-723 in the Treatment of Advanced Solid Tumors
|
Phase 1/Phase 2 | |
Recruiting |
NCT03175224 -
APL-101 Study of Subjects With NSCLC With c-Met EXON 14 Skip Mutations and c-Met Dysregulation Advanced Solid Tumors
|
Phase 2 | |
Recruiting |
NCT06036121 -
A Study of ADRX-0706 in Select Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT03258151 -
Association of Genetic Polymorphisms With Docetaxel-based Chemotherapy Toxicities in Chinese Solid Tumor Patients
|
||
Completed |
NCT01528046 -
Metformin in Children With Relapsed or Refractory Solid Tumors
|
Phase 1 | |
Recruiting |
NCT05325866 -
A Study Evaluating Bemarituzumab in Solid Tumors With Fibroblast Growth Factor Receptor 2b (FGFR2b) Overexpression
|
Phase 1/Phase 2 | |
Recruiting |
NCT04557449 -
Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors
|
Phase 1/Phase 2 | |
Terminated |
NCT02890368 -
Trial of Intratumoral Injections of TTI-621 in Subjects With Relapsed and Refractory Solid Tumors and Mycosis Fungoides
|
Phase 1 | |
Completed |
NCT02759640 -
A Phase I Trial of HS-10241 in Solid Tumors
|
Phase 1 | |
Completed |
NCT02279433 -
A First-in-human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of DS-6051b
|
Phase 1 |