Clinical trial NCT03318562: A PD Study of Oral eFT508 in Subjects With Advanced TNBC and HCC
Official title: A Pharmacodynamic Study of Oral eFT508 in Subjects With Advanced Triple Negative Breast Cancer and Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Triple Negative Breast Cancer
Hepatocellular Carcinoma
Lead sponsor: Effector Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-10-24
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the pharmacodynamic (PD), safety, antitumor activity, and PK of eFT508 in female subjects who have pathologically documented, radiographically measurable, metastatic or locally advanced and unresectable TNBC and have received prior cancer therapy regimen for metastatic disease, and in male and female subjects who have histologically or cytologically confirmed advanced HCC not amenable to surgical resection and have failed systemic therapy.


Eligibility criteria: Inclusion Criteria (TNBC Cohort Only):

* Women ≥18 years of age
* Pathologically documented diagnosis of TNBC that is metastatic or locally advanced and unresectable
* Adequate hepatic function and coagulation profile
* Negative HIV, HBV and HCV

Inclusion Criteria (HCC Cohort Only):

* Men or Women ≥18 years of age
* Histological or cytological confirmed diagnosis of HCC with Barcelona Clinic Liver Cancer Stage B or C who cannot benefit from resection, local ablation, or chemoembolization
* ECOG performance status of 0 or 1
* Has at least 1 measurable lesion based on irRECIST 1.1.
* Negative HIV tests

Inclusion Criteria (Either Cohort):

* subject agrees to undergo a pre-treatment and an on-treatment biopsy of the tumor
* Completion of all previous therapy for the treatment of cancer ≥3 weeks before the start of study drug
* All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before the start of study drug
* Adequate bone marrow and renal function
* Life expectancy of ≥3 months

Exclusion Criteria (Either Cohort):

* Pregnant or breastfeeding
* History of another malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin; in situ cervical carcinoma; 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.
* Gastrointestinal disease that may interfere with drug absorption or with interpretation of GI AEs.
* Known symptomatic brain metastases requiring ≥10 mg/day of prednisolone (or its equivalent).
* Significant cardiovascular disease within 6 months prior to start of study drug
* Ongoing risk for bleeding due to active peptic ulcer disease or bleeding diathesis or requirement for systemic anticoagulation with unfractionated heparin, low-molecular-weight heparin or heparin fractions, or oral anticoagulants.
* Evidence of an ongoing systemic bacterial, fungal, or viral infection
* Has received a live vaccine within 30 days of planned start of study drug
* Major surgery within 4 weeks before the start of study drug
* Prior solid organ or bone marrow progenitor cell transplantation
* Prior therapy with any known inhibitor of MNK1 or MNK2
* Prior high dose chemotherapy requiring stem cell rescue
* History of or active autoimmune disorders or other conditions that might impair or compromise the immune system
* Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids
* Use of a strong inhibitor or inducer of cytochrome P450 (CYP)3A4 within 7 days prior to the start of study drug or expected requirement for use of a strong CYP3A4 inhibitor or inducer during study participation
* Need for proton pump inhibitors and histamine H2 blockers
* Previously received investigational product in a clinical trial within 30 days or within 5 elimination half lives (whichever is longer) prior to the start of study drug, or is planning to take part in another clinical trial while participating in this study
* HCC Cohort Only: Portal vein invasion at the main portal (Vp4), inferior vena cava, or cardiac involvement of HCC based on imaging.

Primary outcomes:
measure: Level of biomarkers of antitumor activation
timeFrame: 28 days
Secondary outcomes:
measure: Molecular profiling of circulating lymphocytes and tumor-infiltrating lymphocytes (TILs)
timeFrame: up to 3 years
measure: Levels of eIF4E and phospho-eIF4E
timeFrame: up to 3 years
measure: Number of mutations
timeFrame: up to 3 years
measure: Objective tumor response
timeFrame: up to 3 years
measure: Progression Free Survival
timeFrame: up to 3 years
measure: Proportion of subjects with TEAEs and SAEs
timeFrame: up to 3 years
measure: PK plasma concentrations
timeFrame: up to 21 weeks
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Kansas City
country: United States
facility: Kansas City Research Institute
state: Missouri
Study officials:
affiliation: CMO
name: Jeremy Barton, MD
role: STUDY_DIRECTOR
References: