Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    eft226
Previous Study | Return to List | Next Study

Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04092673
Recruitment Status : Not yet recruiting
First Posted : September 17, 2019
Last Update Posted : September 17, 2019
Sponsor:
Information provided by (Responsible Party):
Effector Therapeutics

Brief Summary:
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of eFT226 in subjects with selected advanced solid tumor malignancies. The study will evaluate weekly 1-hour intravenous (IV) administration of eFT226. Treatment and study subject evaluations will be performed in 21 day cycles.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: eFT226 Phase 1 Phase 2

Detailed Description:

Part 1 (dose escalation) will enroll subjects with an advanced solid tumor that is refractory or intolerant to standard of care therapy, where the tumor is pancreatic adenocarcinoma (no molecular typing) or any other solid tumor that has a documented activating mutation, amplification, or fusion of HER2, ERBB3, FGFR1, FGFR2, or an activating mutation in KRAS.

Subjects will be assigned sequentially to increasing eFT226 doses. The starting dose of eFT226 is 0.005 mg/kg administered IV weekly in 21 day cycles. eFT226 doses will be escalated in subsequent cohorts after subjects enrolled in a given cohort have completed the 21-day dose-limiting toxicity (DLT) evaluation period. Dose escalation in Part 1 will enroll subjects based on 3+3 design, whereby 3 subjects will be initially enrolled and treated at each dose level.

To obtain as robust a data set as possible regarding PK, safety and tolerability in a diverse population prior to selecting the RP2D, the MTD and MTD-1 cohorts may be backfilled up to 15 subjects total in each cohort.

Part 2 (Expansion Cohort) of the study will provide cohort expansion to further explore the safety, pharmacology, and clinical activity of eFT226 monotherapy in subjects with previously treated advanced solid tumor malignancies. Part 2 will be based on results observed in Part 1 and will be defined by amendment to the protocol.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Intervention Model: Sequential Assignment
Intervention Model Description: dose escalation, 3+3 design
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: sequential escalation
eFT226 is administered IV weekly in 21 day cycles. eFT226 doses will be escalated in sequential cohorts after subjects enrolled in a given cohort have completed the 21-day dose-limiting toxicity (DLT) evaluation period. Starting dose is 0.005mg/kg/week, potentially escalating to 0.12mg/kg/week until MTD and RP2D are established
Drug: eFT226
eFT226 is a novel small-molecule, investigational drug being developed by eFFECTOR Therapeutics as an anticancer therapy. eFT226 is a potent and selective inhibitor of eIF4A1-mediated translation and selectively regulates the translation of a subset of mRNAs based on sequence specific recognition motifs in their 5'-UTR. eIF4A1 inhibition by eFT226 downregulates expression of receptor tyrosine kinases and KRAS, leading to decreased signaling through the PI3K/AKT and MAPK pathways. Preclinical efficacy testing of eFT226 demonstrates activity across models of solid tumor cancers with amplifications in HER2, FGFR1/2 and mutations in KRAS (including breast, NSCLC and CRC).
Other Name: selective translation inhibitor




Primary Outcome Measures :
  1. Incidence of Treatment-emergent adverse events (safety and tolerability) [ Time Frame: Through study completion, on average 12 months ]
    via adverse event monitoring

  2. Incidence of serious adverse events (safety and tolerability) [ Time Frame: Through study completion, on average 12 months ]
    via adverse event monitoring

  3. Establish Maximum Tolerated Dose (MTD) as determined by occurrence of first cycle Dose Limiting Toxicity (DLT) [ Time Frame: Through study completion, on average 12 months ]
    determine MTD by occurrance of DLTs within a 3+3 design or recommended

  4. Establish Recommended Phase 2 Dose (RP2D) [ Time Frame: Through study completion, on average 12 months ]
    Determined by incidence, type, and severity of DLTs, AEs, and SAEs

  5. evaluate plasma PK parameters of eFT226 - maximum concentration (Cmax) [ Time Frame: Through study completion, on average 12 months ]
    Plasma for evaluation of Cmax to be collected at multiple time points

  6. evaluate plasma PK parameters of eFT226 - Area under the plasma concentration -time curve (AUC) [ Time Frame: Through study completion, on average 12 months ]
    Plasma for evaluation of AUC to be collected at multiple time points

  7. evaluate plasma PK parameters of eFT226 - terminal phase half-life (t1/2) [ Time Frame: Through study completion, on average 12 months ]
    Plasma for evaluation of t1/2 to be collected at multiple time points


Secondary Outcome Measures :
  1. antitumor activity and survival [ Time Frame: From start of study therapy to the first documentation of disease progression or death from any cause, which ever came first, assessed up to 100 months ]
    determination of response and progression will be evaluated using RECIST 1.1



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Part 1 (Dose Escalation): Subject has an advanced solid tumor that is refractory or intolerant to standard of care therapy, where the tumor is pancreatic adenocarcinoma (no molecular typing required) or any other solid tumor that has at least one of the following: a documented activating mutation, amplification, or fusion of HER2, ERBB3, FGFR1, FGFR2, or an activating mutation in KRAS; molecular tumor typing can be determined by immunohistochemistry (IHC; at IHC2+ or greater level), fluorescence in situ hybridization (FISH), next generation sequencing, or other analysis methods as appropriate. If the tumor is breast cancer or gastric cancer, subject must have failed treatment with trastuzumab as well as another anti-HER2 agent.
  2. Men and women of age ≥ 18 years
  3. Subject has a life expectancy of 3 months or more.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  5. Has at least 1 measurable lesion per RECIST Version 1.1 criteria.
  6. Completion of all previous therapy (including radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer for 4 weeks (6 weeks for nitrosourea or mitomycin) before the start of study therapy.
  7. All acute toxic effects of any prior antitumor therapy resolved to Grade 1 before the start of study therapy (with the exception of alopecia [Grade ≤ 2 permitted], neurotoxicity [Grade ≤ 2 permitted], or selected laboratory parameters [Grade ≤ 2 permitted with exceptions as noted below])
  8. Adequate bone marrow function:

8a. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L. 8b. Platelet count ≥ 100 × 109/L (Grade ≤ 1). 8c. Hemoglobin ≥ 9.0 g/dL (Grade ≤ 2) maintained for ≥ 2 weeks from any prior transfusion.

9. Adequate hepatic function during Screening as defined below: 9a. Serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN) or ≤5 x ULN if known liver involvement.

9b. Serum aspartate aminotransferase (AST) ≤ 3 x ULN or ≤ 5 x ULN if known liver involvement.

9c. Serum bilirubin ≤ 1.5 x ULN (unless due to Gilbert's syndrome or hemolysis, in which case ≤ 3 x ULN is permitted).

10. Adequate renal function: 10a. Measured or estimated creatinine clearance (eClCR) > 50 mL/min (eClCR to be calculated by the Cockcroft-Gault formula 11. Adequate electrolyte values within 72 hours before the start of study therapy: 11a. Serum potassium within normal limits (WNL). 11b. Serum calcium (adjusted for serum albumin concentration) WNL. 11c. Serum magnesium WNL. Note: Oral or IV supplementation or medical therapy may be used to achieve normal values for serum potassium, calcium and magnesium.

12. Adequate coagulation profile: 12a. Prothrombin time (PT) ≤ 1.5 x ULN (Grade ≤ 1). 12b. Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (Grade ≤ 1).

13. For female subjects of childbearing potential, a negative serum pregnancy test within 7 days prior to start of study therapy.

14. For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until ≥ 30 days after the final dose of study therapy. Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and follicle-stimulating hormone [FSH] levels within the institutional laboratory postmenopausal range and a negative serum or urine beta human chorionic gonadotropin [βHCG]); or is menopausal (age ≥ 55 years with amenorrhea for ≥ 6 months).

15. For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol-recommended method of contraception from the start of study therapy until ≥ 30 days after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥ 90 days after administration of the final dose of study therapy. Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy.

16. In the judgment of the Investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current disease status, medical condition, and the potential benefits and risks of alternative treatments for the subject's cancer.

17. Willingness and ability to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.

Exclusion Criteria:

  1. History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; adequately treated carcinoma in situ without evidence of disease; adequately treated papillary, noninvasive bladder cancer; other adequately treated Stage 1 or 2 cancers currently in complete remission; or any other cancer that has been in complete remission for ≥ 2 years.
  2. Previously documented or current brain metastases that have not been treated.
  3. Significant cardiovascular disease (eg, myocardial infarction, arterial thromboembolism, cerebrovascular thromboembolism) within 6 months prior to start of study therapy; symptomatic dysrhythmias or unstable dysrhythmias requiring medical therapy; unstable angina; symptomatic peripheral vascular disease; New York Heart Association Class 3 or 4 congestive heart failure; uncontrolled Grade ≥ 3 hypertension (diastolic blood pressure ≥ 100 mmHg or systolic blood pressure ≥ 160 mmHg) despite antihypertensive therapy; or history of congenital prolonged QT syndrome.
  4. Significant screening ECG abnormalities, including unstable cardiac arrhythmia requiring medication, left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree AV block, Grade ≥ 2 bradycardia, or corrected QT (QTcF) > 450 msec (based on the average of 3 measurements at 5-minute intervals).
  5. Evidence of an ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections) at the time of start of study therapy. Note: Subjects with localized fungal infections of skin or nails are eligible.
  6. Known active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. Note: Negative Hep B surface antigen and negative Hep B core antibody or undetectable Hep B virus DNA per qPCR testing; Negative Hep C virus antibody or negative HCV RNA by qPCR testing; Negative HIV antibody.
  7. Pregnancy or breastfeeding.
  8. Major surgery within 4 weeks before the start of study therapy or not fully recovered from major surgery.
  9. Prior solid organ transplantation.
  10. Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids. Note: At screening, subjects may be using systemic corticosteroids (at doses of ≤ 10 mg of prednisone or equivalent) or topical or inhaled corticosteroids. During study therapy, subjects may use systemic, enteric, topical or enteric corticosteroids as required for treatment-emergent conditions.
  11. Use of a known QT-prolonging drugs during screening or expected requirement for use during study therapy
  12. Use of a strong or moderate inhibitor or inducer of cytochrome P450 (CYP) 3A4 within 7 days prior to the start of study therapy or expected requirement for use of a strong or moderate inhibitor or inducer of CYP3A4 during study therapy.
  13. Concurrent participation in another therapeutic clinical trial.
  14. Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04092673


Contacts
Layout table for location contacts
Contact: Lyon Gleich, MD 1-513-579-9911 ext 12400 L.Gleich@Medpace.com

Locations
Layout table for location information
United States, Ohio
University of Toledo Not yet recruiting
Toledo, Ohio, United States, 43606
Contact: John Nemunaitis, MD         
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
NEXT Oncology Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Raghad Karim, MD    210-580-9500      
Sponsors and Collaborators
Effector Therapeutics
Investigators
Layout table for investigator information
Study Director: Lyon Gleich, MD Medpace, Inc.

Layout table for additonal information
Responsible Party: Effector Therapeutics
ClinicalTrials.gov Identifier: NCT04092673     History of Changes
Other Study ID Numbers: eFT226-0002
First Posted: September 17, 2019    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is not a plan to make IPD available

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasms