Advanced Stage Solid TumorsPhase 1NCT02160106
First in Human Dose Escalation Study of Vactosertib (TEW-7197) in Subjects With Advanced Stage Solid Tumors
A Phase 1 study testing TEW-7197 in people with Advanced Stage Solid Tumors, run by MedPacto, Inc. at 3 sites in United States.
Trial summary
The phase I dose escalation study will investigate the safety, tolerability, and pharmacokinetics of the TGF-β pathway inhibitor TEW 7197 in subjects with advanced, refractory solid tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Stage Solid Tumors
- What is being tested?
- TEW-7197
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 3 sitesUnited States
- Study dates
- 29 Jul 2014to 28 Aug 2018
- Phase
- Phase 1
- 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
- Advanced stage solid tumors as documented by histological or cytological evidence, with no available approved therapies known to cure metastatic disease or extend survival, and who have received all standard therapy.
- Documented disease progression following prior therapy, as assessed by the Investigator.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Evaluable or measurable disease as defined by RECIST v1.1 may be enrolled in the dose escalation part; for the dose confirmation part, subjects must have measurable disease by RECIST v1.1 or biomarker for response.
- Males and females ≥ 18 years of age.
- Able to give written informed consent.
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- Able to swallow tablets.
- Willing and able to comply with scheduled visits, treatment plans, laboratory tests and procedures.
- Acceptable liver function:
- Bilirubin ≤ 1.5 times the upper limit of normal (ULN),
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the ULN; if liver metastases are present, then ≤ 5 times the ULN is allowed.
- Acceptable renal function:
- Serum creatinine ≤ 1.5 times the ULN.
- Acceptable hematologic status (without growth factor support or transfusion dependency):
- Absolute neutrophil count (ANC) ≥ 1,500 cells/μL,
- Platelet count ≥ 100,000/μL,
- Hemoglobin ≥ 9.0 g/dL.
- QTc interval calculated according to Fridericia's formula (QTcF = QT/RR0.33; RR = RR interval) of ≤ 450 msec on screening electrocardiogram (ECG).
- Must have a normal ejection fraction (within the reference range of the institution) and no clinically significant valvular dysfunction.
- Must have discontinued cancer treatments, including experimental agents for 28 days or a minimum of 5 half-lives (for any biologics) prior to the start of treatment. Enrollment after exposure levels of a biologic have fallen below an active level as established in the summary basis of approval is acceptable.
- Must have discontinued radiotherapy at least 14 days with resolution of any toxicity to Grade 1 or better prior to the start of treatment.
- A life expectancy of at least 3 months as assessed by the Investigator.
- Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study drug. For the purpose of this study, female subjects of childbearing potential are defined as all female subjects after puberty unless they are postmenopausal for at least 1 year, or are surgically sterile (hysterectomy or bilateral oophorectomy or tubal ligation).
Who cannot join
- Elevated Troponin 1 levels at screening or known to have persistently elevated brain natriuretic peptide (BNP).
- Serious pre-existing medical conditions as follows:
- Myocardial infarction within 6 months prior to screening, or pericardial effusion,
- History of cardiac or aortic surgery,
- Serious arrhythmia,
- Unstable angina pectoris,
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- Congestive heart failure of New York Heart Association class III/IV,
- Hypertension that is not controlled by standard medication (to 150/90 mmHg or below),
- Cirrhosis of the liver, Child-Pugh Stage B or C, or history of liver transplant,
- Severe diabetes that is not currently controlled,
- Current or history of interstitial pneumonitis,
- Presence of aneurisms of the ascending aorta or aortic stress.
- Uncontrolled metastatic disease to the brain or central nervous system (CNS).
- Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
- Received prior treatment targeting the signaling pathway of TGF-β.
- Major abnormalities identified by ECG or echocardiogram (ECHO), at the Investigator's discretion.
- Known infection of, or who test positive for, human immunodeficiency virus, hepatitis B virus or hepatitis C virus.
- Active infection requiring systemic antibiotic therapy.
- Known substance abuse or receiving concurrent treatment with non-permitted drugs.
- Female subjects who are breastfeeding, or intend to breastfeed during the duration of the study and for 30 days following the last dose of study drug.
- Known history, or suspected hypersensitivity to any excipients.
- Female subjects must not be pregnant or at risk to become pregnant during the study. Fertile male and female subjects must agree to use an effective barrier method of birth control to avoid pregnancy (for female subjects a double-barrier method of contraception, for male subjects a condom with spermicide) or total abstinence from the time of providing informed consent until 90 days after the last administration of study drug. Use of oral contraceptives is not allowed.
- Any other serious medical condition which in the Investigator's opinion would preclude safe participation in the study.
- Subjects, in the opinion of the Investigator, who are unsuitable to participate in the study.
- Currently using or planning to use:
- Drugs which are exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4 (CYP)3A4.
- Drugs which are exclusively or primarily eliminated by UDP glucuronyltransferase 1A1 (UGT)1A1.
- Drugs which are substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a narrow therapeutic window; or which are strong inhibitors of drug transporter MDR1.
- Any major surgeries within 28 days.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Study site
Durham, North Carolina, 27710
Study site
Nashville, Tennessee, 37203
Study site
Nashville, Tennessee, 37232
About this study
Official title: First-in-Human Dose-Escalation Study of Vactosertib (TEW-7197) Monotherapy in Subjects With Advanced Stage Solid Tumors
The phase I dose escalation study will investigate the safety, tolerability, and pharmacokinetics of the TGF-β pathway inhibitor TEW 7197 in subjects with advanced, refractory solid tumors.
Read the detailed description
This is an open-label, multicenter, dose-escalation, phase I study of TEW-7197 in subjects with advanced solid tumors. The study will investigate the safety, tolerability, and pharmacokinetics of TEW-7197, and will define the maximum tolerated dose (MTD) of TEW-7197 using a 3 + 3 design. An expansion phase at the MTD will identify the recommended phase 2 dose, with an emphasis on subjects with melanoma, breast cancer, hepatocellular carcinoma, and prostate cancer. TEW-7197 is an orally bioavailable small molecule that inhibits protein serine/threonine kinase of activin receptor-like kinase 5 (ALK5) and blocks intracellular signaling of TGF-β by inhibiting the phosphorylation of ALK5 substrates.
- Conditions
- Advanced Stage Solid Tumors
- Being tested
- TEW-7197
- Keywords
- Cancer, advanced solid tumors, metastatic, phase I, transforming growth factor beta, TGF-β, first-in-human, TEW-7197, activin receptor-like kinase 5, ALK5, Smad2, Smad3, phospho-Smad, phospho Smad, psmad, serine / threonine kinase inhibitor, pharmacokinetics, MedPacto, National OncoVenture
- Medical subject headings
- Neoplasms, Neoplasm Metastasis, Camurati-Engelmann Syndrome, Keratoacanthoma familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEW-7197Drug
Also called EW-7197, EW7197
Single daily doses by oral administration on Days 1, 2, 3, 4, 5, Days 8, 9, 10, 11, 12, Days 15, 16, 17, 18, 19 and Days 22, 23, 24, 25, 26 of each 28 day cycle. Starting dose is 30 mg, with escalation to 60 mg, and subsequent dose escalation using a modified Fibonacci algorithm.
| Study group | Role | What they receive |
|---|---|---|
| TEW-7197 | Experimental | Dose Escalation of TEW-7197: TEW 7191 tablets will be given once daily (QD) or twice daily (BID) for 5 days followed by 2 days without treatment in 28-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons. Receives: Drug: TEW-7197 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) based on the number of subjects experiencing at least 1 DLT
Measured: 28 days
Secondary outcomes (1)
Dose-dependency of toxicity based on: dose limiting toxicities; frequency, type, grade, and seriousness, and causality of treatment-emergent adverse events, and laboratory assessments.
Measured: while undergoing study treatment and up to 30 days after the last dose of TEW-7197
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2014 (estimated)
- Study start29 Jul 2014
- Primary completion31 Jul 2018
- Study completion28 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Stage Solid TumorsStudies 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- MedPacto, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National OncoVenture
- Responsible party
- Sponsor
- Investigators
- Ilho Ha, PhD, Study chair, MedPacto, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02160106
- Sponsor's protocol ID
- MP-001
- Status last verified
- May 2019
- First submitted
- 5 Jun 2014
- Last updated
- 9 May 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- First-in-Human Dose-Escalation Study of Vactosertib (TEW-7197) Monotherapy in Subjects With Advanced Stage Solid Tumors
- ClinicalTrials.gov ID
- NCT02160106
- Acronym / sponsor ID
- MP-001
- Conditions
- Advanced Stage Solid Tumors
- Keywords
- Cancer, advanced solid tumors, metastatic, phase I, transforming growth factor beta, TGF-β, first-in-human, TEW-7197
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- MedPacto, Inc.Industry (pharma, biotech, devices)
- Collaborators
- National OncoVenture
- Study start
- 29 Jul 2014 (actual)
- Primary completion
- 31 Jul 2018 (actual)
- Study completion
- 28 Aug 2018 (actual)
- First posted
- 10 Jun 2014 (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.
The phase I dose escalation study will investigate the safety, tolerability, and pharmacokinetics of the TGF-β pathway inhibitor TEW 7197 in subjects with advanced, refractory solid tumors.
Detailed description
This is an open-label, multicenter, dose-escalation, phase I study of TEW-7197 in subjects with advanced solid tumors. The study will investigate the safety, tolerability, and pharmacokinetics of TEW-7197, and will define the maximum tolerated dose (MTD) of TEW-7197 using a 3 + 3 design. An expansion phase at the MTD will identify the recommended phase 2 dose, with an emphasis on subjects with melanoma, breast cancer, hepatocellular carcinoma, and prostate cancer. TEW-7197 is an orally bioavailable small molecule that inhibits protein serine/threonine kinase of activin receptor-like kinase 5 (ALK5) and blocks intracellular signaling of TGF-β by inhibiting the phosphorylation of ALK5 substrates.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TEW-7197 | Experimental | Drug: TEW-7197Dose Escalation of TEW-7197: TEW 7191 tablets will be given once daily (QD) or twice daily (BID) for 5 days followed by 2 days without treatment in 28-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Advanced stage solid tumors as documented by histological or cytological evidence, with no available approved therapies known to cure metastatic disease or extend survival, and who have received all standard therapy.
- Documented disease progression following prior therapy, as assessed by the Investigator.
- Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Evaluable or measurable disease as defined by RECIST v1.1 may be enrolled in the dose escalation part; for the dose confirmation part, subjects must have measurable disease by RECIST v1.1 or biomarker for response.
- Males and females ≥ 18 years of age.
Key exclusion criteria (29 listed)
- Elevated Troponin 1 levels at screening or known to have persistently elevated brain natriuretic peptide (BNP).
- Serious pre-existing medical conditions as follows:
- Uncontrolled metastatic disease to the brain or central nervous system (CNS).
- Known history of difficulty swallowing, malabsorption or other conditions that may reduce absorption of the product.
- Received prior treatment targeting the signaling pathway of TGF-β.
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 |
|---|---|---|
| TEW-7197Also: EW-7197, EW7197Single daily doses by oral administration on Days 1, 2, 3, 4, 5, Days 8, 9, 10, 11, 12, Days 15, 16, 17, 18, 19 and Days 22, 23, 24, 25, 26 of each 28 day cycle. Starting dose is 30 mg, with escalation to 60 mg, and subsequent dose escalation using a modified Fibonacci algorithm. | Drug | TEW-7197 |
Primary outcome
Maximum tolerated dose (MTD) based on the number of subjects experiencing at least 1 DLT
Time frame: 28 days
1 secondary outcome
Dose-dependency of toxicity based on: dose limiting toxicities; frequency, type, grade, and seriousness, and causality of treatment-emergent adverse events, and laboratory assessments.
Time frame: while undergoing study treatment and up to 30 days after the last dose of TEW-7197
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2019.
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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.
Ilho Ha, PhD study chair
MedPacto, Inc.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TEW-7197 in people with Advanced Stage Solid Tumors, run by MedPacto, Inc. at 3 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 23 inclusion and 29 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: finished, as of the sponsor's last update on 9 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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) based on the number of subjects experiencing at least 1 DLT (time frame: 28 days). 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 9 May 2019.