Desmoid TumorPhase 1/2NCT03802084
A Study to Evaluate the Safety and Efficacy of Vactosertib and Imatinib in Patients With Advanced Desmoid Tumor
A Phase 1/2 study testing vactosertib/imatinib combination in people with Desmoid Tumor, run by Hyo Song Kim at 1 site in South Korea.
Trial summary
This is a phase I/II, open-label, non-randomized, multicentre study to evaluate the clinical activity of vactosertib plus imatinib in desmoid tumor. Based on the background, TGF-β inhibition as a potential therapeutic target for desmoid tumor and convey significant implications for the clinical development. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Desmoid Tumor
- What is being tested?
- vactosertib/imatinib combination
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSouth Korea
- Study dates
- 15 Apr 2019to 26 Mar 2024
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed desmoid tumor (aggressive fibromatosis) not available for local treatment (surgical resection or radiation therapy)
- Eastern Cooperative Oncology Group performance status of 0-1
- Measurable lesion (RECIST 1.1.)
- Patients with sufficient organ function according to laboratory findings
- Hemoglobin ≥ 9.0 g/dL
- Neutrophils ≥ 1000 /µL
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- Platelets ≥ 75,000/µL
- Total Bilirubin ≤ 1.5 × UNL (upper normal limit): For patients with liver metastases, ≤2
- Serum creatinine ≤1.5 X ULN or > 1.5 X Creatinine Clearance ≥50 mL/min for ULN patients (based on 24-hour urinalysis or Cockroft-Gault Formula calculations)
- AST(SGOT)/ALT(SGPT) ≤ 3.0 × UNL or ≤ 5.0 × UNL (for patients with liver or bone metastases)
- Alkaline Phosphatase (ALP): ≤ 3.0 × UNL or ≤ 5.0 × UNL (for patients with liver or bone metastases)
- All patients must be able to provide a newly acquired tumor biopsy during screening (preferred) or provide an available tumor sample taken ≤3 years prior to screening.
- Subjects must have ejection fraction ≥ 50% and no clinically significant valvular dysfunction
Who cannot join
- Previous TGF-β inhibitor exposed patient
- Patient who has had chemotherapy, radiotherapy, or biological therapy within 2 weeks
- Any unresolved chronic toxicity greater than grade 2 from previous anticancer therapy.
- Has an active infection requiring systemic therapy
- Uncontrolled intercurrent illness, including symptomatic congestive heart failure (NYHA Class III/IV), uncontrolled hypertension (≥150/90mmHg), unstable angina pectoris or myocardial infarction (≤ 6 months prior to screening), uncontrolled cardiac arrhythmia, cardiac valulopathy
- Uncontrolled or active central nervous system metastasis and/or carcinomatous meningitis
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- Child-Pugh B or C liver cirrhosis
- History of another primary malignancy.
- Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of investigational product(IP).
- Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product(IP).
- Current or prior use of immunosuppressive medication within 14 days before the first investigational product(IP).
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Severance Hospital, Yonsei University Health System
Seoul, 03722
About this study
Official title: A Phase 1b/2a, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination With Imatinib in Patients With Advanced Desmoid Tumor (Aggressive Fibromatosis)
This is a phase I/II, open-label, non-randomized, multicentre study to evaluate the clinical activity of vactosertib plus imatinib in desmoid tumor. Based on the background, TGF-β inhibition as a potential therapeutic target for desmoid tumor and convey significant implications for the clinical development. Therefore, investigator will conduct the phase II trial of vactosertib in combined with imatinib in desmoid tumor.
Read the detailed description
Desmoid tumor (aggressive fibromatosis) is a mesenchymal neoplasm associated with mutations, resulting in -catenin-mediated transcriptional activation. It is composed of a clonal proliferation of mesenchymal, fibroblast-like cells occurred sporadic or as a part of familial adenomatosis polyposis. This tumor has high local recurrence rate after complete excision (~40%). Therefore, although lacking metastatic capability, patients experience repeated recurrence with attendant severe morbidity. Various systemic therapy using NSAID, cytotoxic agent (doxorubicin and vinblastine), biologic agents (tamoxifen, low-dose interferon), and tyrosine kinase inhibitors (imatinib) are recommended with modest activity. Among them, imatinib has shown promising activity and approved as standard treatment for desmoid tumor. However, still there is modest response (10-15% responses) and further combination strategy is warranted to improve antitumor efficacy.
The transforming growth factor-β (TGF-β) family of cytokines has 33 members in humans, including TGF-β isoforms, activins, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs). These factors regulate growth, survival, differentiation and migration of cells, and have important roles during embryonal development and in the control of adult tissue homeostasis. During carcinogenesis, TGF-β has a dual role; initially it suppresses tumorigenesis by inducing growth arrest and promoting apoptosis, however, in advanced cancers, where TGF-β often is overexpressed. In addition, TCGA (the cancer genome atlas) pan-cancer also demonstrated high expression of TGF-β responsive signature in desmoid tumor. Regarding the combination, TEW-7197 (vactosertib), a TGF-β inhibitor and imatinib demonstrated synergistic effect in vitro and xenograft model. Compared to imatinib alone, administration of imatinib plus vactosertib to mice significantly delayed disease relapse and prolonged survival. Collectively, these results indicate that vactosertib may be a promising candidate for a new therapeutic strategy.
Based on the background, TGF-β inhibition as a potential therapeutic target for desmoid tumor and convey significant implications for the clinical development. Therefore, investigator will conduct the phase II trial of vactosertib in combined with imatinib in desmoid tumor.
- Conditions
- Desmoid Tumor
- Being tested
- vactosertib/imatinib combination
- Medical subject headings
- Desmoid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
vactosertib/imatinib combinationDrug
Phase 1 : Imatinib 400mg QD P q28days Vactosertib 1 cohort 200mg bid (D1-5, 8-12, 15-19, 22-26)
- 1 cohort 100mg bid Phase 2 : Imatinib 400mg QD PO q28days. Vactosertib RP2D, bid (D1-5, 8-12, 15-19, 22-26)
| Study group | Role | What they receive |
|---|---|---|
| vactosertib/imatinib combination | Experimental | Not described Receives: Drug: vactosertib/imatinib combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
adverse event
to evaluate the safety and tolerability
Measured: 4 weeks
clinical benefit rate was determined using RECIST 1.1
to evaluate antitumor activity by determining progression-free survival
Measured: 16weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2019
- Study start15 Apr 2019
- Primary completion26 Mar 2024
- Study completion26 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Desmoid TumorStudies 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
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hyo Song Kim
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Hyo Song Kim, Yonsei University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03802084
- Sponsor's protocol ID
- 4-2018-0807
- Status last verified
- May 2024
- First submitted
- 7 Jan 2019
- Last updated
- 13 May 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b/2a, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Vactosertib in Combination With Imatinib in Patients With Advanced Desmoid Tumor (Aggressive Fibromatosis)
- ClinicalTrials.gov ID
- NCT03802084
- Acronym / sponsor ID
- 4-2018-0807
- Conditions
- Desmoid Tumor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hyo Song KimUniversity, hospital or other
- Study start
- 15 Apr 2019 (actual)
- Primary completion
- 26 Mar 2024 (actual)
- Study completion
- 26 Mar 2024 (actual)
- First posted
- 14 Jan 2019 (actual)
- 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 is a phase I/II, open-label, non-randomized, multicentre study to evaluate the clinical activity of vactosertib plus imatinib in desmoid tumor. Based on the background, TGF-β inhibition as a potential therapeutic target for desmoid tumor and convey significant implications for the clinical development. Therefore, investigator will conduct the phase II trial of vactosertib in combined with imatinib in desmoid tumor.
Detailed description
Desmoid tumor (aggressive fibromatosis) is a mesenchymal neoplasm associated with mutations, resulting in -catenin-mediated transcriptional activation. It is composed of a clonal proliferation of mesenchymal, fibroblast-like cells occurred sporadic or as a part of familial adenomatosis polyposis. This tumor has high local recurrence rate after complete excision (~40%). Therefore, although lacking metastatic capability, patients experience repeated recurrence with attendant severe morbidity. Various systemic therapy using NSAID, cytotoxic agent (doxorubicin and vinblastine), biologic agents (tamoxifen, low-dose interferon), and tyrosine kinase inhibitors (imatinib) are recommended with modest activity. Among them, imatinib has shown promising activity and approved as standard treatment for desmoid tumor. However, still there is modest response (10-15% responses) and further combination strategy is warranted to improve antitumor efficacy.
The transforming growth factor-β (TGF-β) family of cytokines has 33 members in humans, including TGF-β isoforms, activins, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs). These factors regulate growth, survival, differentiation and migration of cells, and have important roles during embryonal development and in the control of adult tissue homeostasis. During carcinogenesis, TGF-β has a dual role; initially it suppresses tumorigenesis by inducing growth arrest and promoting apoptosis, however, in advanced cancers, where TGF-β often is overexpressed. In addition, TCGA (the cancer genome atlas) pan-cancer also demonstrated high expression of TGF-β responsive signature in desmoid tumor. Regarding the combination, TEW-7197 (vactosertib), a TGF-β inhibitor and imatinib demonstrated synergistic effect in vitro and xenograft model. Compared to imatinib alone, administration of imatinib plus vactosertib to mice significantly delayed disease relapse and prolonged survival. Collectively, these results indicate that vactosertib may be a promising candidate for a new therapeutic strategy.
Based on the background, TGF-β inhibition as a potential therapeutic target for desmoid tumor and convey significant implications for the clinical development. Therefore, investigator will conduct the phase II trial of vactosertib in combined with imatinib in desmoid tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| vactosertib/imatinib combination | Experimental | Drug: vactosertib/imatinib combination |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically confirmed desmoid tumor (aggressive fibromatosis) not available for local treatment (surgical resection or radiation therapy)
- Eastern Cooperative Oncology Group performance status of 0-1
- Measurable lesion (RECIST 1.1.)
- Patients with sufficient organ function according to laboratory findings
- All patients must be able to provide a newly acquired tumor biopsy during screening (preferred) or provide an available tumor sample taken ≤3 years prior to screening.
Key exclusion criteria (11 listed)
- Previous TGF-β inhibitor exposed patient
- Patient who has had chemotherapy, radiotherapy, or biological therapy within 2 weeks
- Any unresolved chronic toxicity greater than grade 2 from previous anticancer therapy.
- Has an active infection requiring systemic therapy
- Uncontrolled intercurrent illness, including symptomatic congestive heart failure (NYHA Class III/IV), uncontrolled hypertension (≥150/90mmHg), unstable angina pectoris or myocardial infarction (≤ 6 months prior to screening), uncontrolled cardiac arrhythmia, cardiac valulopathy
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 |
|---|---|---|
| vactosertib/imatinib combinationPhase 1 : Imatinib 400mg QD P q28days Vactosertib 1 cohort 200mg bid (D1-5, 8-12, 15-19, 22-26) * 1 cohort 100mg bid Phase 2 : Imatinib 400mg QD PO q28days. Vactosertib RP2D, bid (D1-5, 8-12, 15-19, 22-26) | Drug | vactosertib/imatinib combination |
Primary outcome
adverse event
Time frame: 4 weeks
to evaluate the safety and tolerability
clinical benefit rate was determined using RECIST 1.1
Time frame: 16weeks
to evaluate antitumor activity by determining progression-free survival
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 13 May 2024.
- Individual participant dataSharing planned: No
Related trials for Desmoid Tumor
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FOG-001 in Locally Advanced or Metastatic Solid Tumors
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Active, not recruitingPhase 2
A Study of a New Drug, Nirogacestat, for Treating Desmoid Tumors That Cannot be Removed by Surgery
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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 vactosertib/imatinib combination in people with Desmoid Tumor, run by Hyo Song Kim at 1 site in South Korea.
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 13 inclusion and 11 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 13 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. 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 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?
adverse event (time frame: 4 weeks). 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 13 May 2024.