CancerPhase 1/2NCT02605083
A Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
A Phase 1/2 study testing eFT508 in people with Cancer, run by Effector Therapeutics at 4 sites in United States.
Trial summary
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of eFT508. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer
- What is being tested?
- eFT508
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 66 participants
- Where
- 4 sitesUnited States
- Study dates
- 3 Dec 2015to 22 Mar 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Pathologically documented diagnosis of advanced solid tumor malignancy that progressed after appropriate prior therapy or has no potential for cure with currently available treatments.
- Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) outside of any prior radiation field.
- At least 3 weeks post any treatments/therapies at the time of first dose.
- Adequate bone marrow function.
- Adequate hepatic function.
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- Adequate renal function.
- Normal coagulation panel.
- Negative antiviral serology.
- Willingness to use effective contraception.
Who cannot join
- Known central nervous system malignancy.
- Gastrointestinal disease that may interfere with drug absorption.
- Significant cardiovascular disease.
- Significant ECG abnormalities.
- Ongoing risk of bleeding due to active peptic ulcer disease, bleeding diathesis, or requirement for systemic anticoagulants. Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
- Ongoing systemic bacterial, fungal or viral infection (with the exception of fungal infections of the skin or nails).
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- Pregnancy or breastfeeding.
- Major surgery within 4 weeks before the start of study therapy.
- Prior solid organ or bone marrow progenitor cell transplantation.
- Prior therapy with any known inhibitor of MNK1 or MNK2.
- Ongoing immunosuppressive therapy, including systemic or enteric corticosteroids (can be using topical or inhaled corticosteroids).
- Use of drugs that might pose a risk of a drug-drug interaction within 4-7 days before the start of study therapy.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
SCRI at HealthONE
Denver, Colorado, 80218
MD Anderson Cancer Center
Houston, Texas, 77030
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Florida Cancer Specialists
Sarasota, Florida, 34232
About this study
Official title: A Phase 1-2 Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of eFT508.
Read the detailed description
eFT508 is an oral, potent and highly selective inhibitor of mitogen-activated protein kinase interacting kinase (MNK) 1 and 2. Dysregulated translation of messenger RNA (mRNA) plays a role in the pathogenesis of multiple solid tumors and hematological malignancies. MNK1 and MNK2 integrate signals from several oncogenic and immune signaling pathways (including RAS, p38 and Toll-like receptors) by phosphorylating eukaryotic initiation of factor 4E (eIF4E) and key effector proteins. Phosphorylation of these regulatory proteins by MNK1 and MNK2 selectively regulates the stability and translation of a subset of cellular mRNA that control tumor growth, the tumor microenvironment and immune signaling. Nonclinical studies indicate that eFT508 shows activity against various types of solid tumors. These nonclinical studies support initiation of clinical development of eFT508 in patients with cancer.
- Conditions
- Cancer
- Being tested
- eFT508
- Keywords
- Cancer, Neoplasm, Solid Tumor, Breast, Head and Neck, Lung, Pancreatic, Hepatic, Melanoma, Colon, Renal, Thyroid, Prostate, Ovarian, MNK1, MNK2, eIF4E
- Medical subject headings
- Neoplasms, Melanoma, Thyroid Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eFT508Drug
Will be given orally once or twice daily. Each treatment cycle = 21 days.
| Study group | Role | What they receive |
|---|---|---|
| eFT508 | Experimental | Escalation cohort Receives: Drug: eFT508 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)/Recommended dose (RD)
Measured: Up to one year
Overall response rate (ORR)
Measured: Up to three years
Secondary outcomes (5)
Safety (Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03))
Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03)
Measured: Up to three year
Plasma concentration of eFT508 as characterized by maximum serum concentration (Cmax)
Measured: Different time points up to 336 hours
Plasma concentration of eFT508 as characterized by Area Under the Curve (AUC)
Measured: Different time points up to 336 hours
Changes in eIF4E phosphorylation in peripheral blood cells (PBMCs)
Measured: Up to Day 14
Tumor control evaluated by modified RECIST criteria v 1.1
Measured: Up to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2015 (estimated)
- Study start3 Dec 2015
- Primary completion11 Jan 2019
- Study completion22 Mar 2019
Why it stopped: The study was terminated after determination of the RP2D, prior to opening expansion cohorts)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 66 participants (actual)
Sponsor and investigators
- Lead sponsor
- Effector Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jeremy Barton, MD, Study director, Effector Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02605083
- Sponsor's protocol ID
- eFT508-0001
- Status last verified
- Oct 2020
- First submitted
- 9 Nov 2015
- Last updated
- 2 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2 Dose Escalation and Cohort-Expansion Study of Oral eFT508 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT02605083
- Acronym / sponsor ID
- eFT508-0001
- Conditions
- Cancer
- Keywords
- Cancer, Neoplasm, Solid Tumor, Breast, Head and Neck, Lung, Pancreatic, Hepatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated after determination of the RP2D, prior to opening expansion cohorts)
- Enrolment
- 66 participants (actual)
- Lead sponsor
- Effector TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 3 Dec 2015 (actual)
- Primary completion
- 11 Jan 2019 (actual)
- Study completion
- 22 Mar 2019 (actual)
- First posted
- 16 Nov 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of daily oral administration of eFT508.
Detailed description
eFT508 is an oral, potent and highly selective inhibitor of mitogen-activated protein kinase interacting kinase (MNK) 1 and 2. Dysregulated translation of messenger RNA (mRNA) plays a role in the pathogenesis of multiple solid tumors and hematological malignancies. MNK1 and MNK2 integrate signals from several oncogenic and immune signaling pathways (including RAS, p38 and Toll-like receptors) by phosphorylating eukaryotic initiation of factor 4E (eIF4E) and key effector proteins. Phosphorylation of these regulatory proteins by MNK1 and MNK2 selectively regulates the stability and translation of a subset of cellular mRNA that control tumor growth, the tumor microenvironment and immune signaling. Nonclinical studies indicate that eFT508 shows activity against various types of solid tumors. These nonclinical studies support initiation of clinical development of eFT508 in patients with cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| eFT508 | Experimental | Drug: eFT508Escalation cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Pathologically documented diagnosis of advanced solid tumor malignancy that progressed after appropriate prior therapy or has no potential for cure with currently available treatments.
- Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) outside of any prior radiation field.
- At least 3 weeks post any treatments/therapies at the time of first dose.
- Adequate bone marrow function.
Key exclusion criteria (12 listed)
- Known central nervous system malignancy.
- Gastrointestinal disease that may interfere with drug absorption.
- Significant cardiovascular disease.
- Significant ECG abnormalities.
- Ongoing risk of bleeding due to active peptic ulcer disease, bleeding diathesis, or requirement for systemic anticoagulants. Use of heparin or thrombolytic agents for local maintenance or clearance of a central venous catheter is permitted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| eFT508Will be given orally once or twice daily. Each treatment cycle = 21 days. | Drug | eFT508 |
Primary outcome
Maximum tolerated dose (MTD)/Recommended dose (RD)
Time frame: Up to one year
Overall response rate (ORR)
Time frame: Up to three years
5 secondary outcomes
Safety (Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE v. 4.03))
Time frame: Up to three year
Plasma concentration of eFT508 as characterized by maximum serum concentration (Cmax)
Time frame: Different time points up to 336 hours
Plasma concentration of eFT508 as characterized by Area Under the Curve (AUC)
Time frame: Different time points up to 336 hours
Changes in eIF4E phosphorylation in peripheral blood cells (PBMCs)
Time frame: Up to Day 14
Tumor control evaluated by modified RECIST criteria v 1.1
Time frame: Up to three years
Results and safety
The study was stopped early (reason given: The study was terminated after determination of the RP2D, prior to opening expansion cohorts)). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeremy Barton, MD study director
Effector Therapeutics
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing eFT508 in people with Cancer, run by Effector Therapeutics at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated after determination of the RP2D, prior to opening expansion cohorts)). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD)/Recommended dose (RD) (time frame: Up to one year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2020.