Vactosertib and Imatinib Combination in Patients with Advanced Desmoid Tumor/aggressive Fibromatosis (DT/AF)

NCT06219733 | Withdrawn Phase 2

• 1 other identifier: MP-VAC-206
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Vactosertib and imatinib combination in patients with advanced desmoid tumor/aggressive fibromatosis (DT/AF) compared with imatinib monotherapy

Conditions

Dermoid

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  To evaluate the progression-free survival (PFS) of vactosertib and imatinib combination compared with imatinib alone up to 2 years. The subject will be assessed until disease progression is observed or death, which comes first. The disease progression will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Criteria. The date of progression will be determined by a blinded, independent, central radiologic review (BICR).

  28 days

Study Arms (2)

Vactosertib and imatinib combination

EXPERIMENTAL

Vactosertib 200 mg PO BID 5 days on / 2 days off in combination with imatinib 400 mg PO QD daily

Drug: Vactosertib

Imatinib alone

ACTIVE COMPARATOR

Imatinib 400 mg PO QD daily

Drug: Imatinib

Interventions

Vactosertib DRUG

200 mg PO BID 5 days on / 2 days off

Vactosertib and imatinib combination

Imatinib DRUG

Imatinib 400 mg PO QD daily

Imatinib alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Have diagnosed with DT/AF histologically.
• Meet one of the following criteria to be eligible:
• Progression by radiographic image by RECIST v1.1 or increase in tumor size equal to, or greater than (≥) 10% within 6 months prior to C1D1
• Patients with documented symptomatic disease related to DT/AF including pain, limitation of function, etc.
• Have at least one measurable lesion based on RECIST v1.1: Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have a performance status of ≤ 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.
• Be able to swallow tablets and absorb vactosertib and imatinib.
• Have adequate organ function as indicated by the following laboratory values
• Have no history of additional malignancy that is progressing or has required active treatment within the past 3 years, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cervical cancer, or have undergone potentially curative therapy with no evidence of that disease recurrence.
• Be able to provide a newly acquired (within 6 months prior to C1D1) tumor sample during screening (preferred) or provide an available archived tumor sample. At least 10 subjects in each treatment group should be able to provide newly acquired (within 6 months prior to C1D1) tumor sample. Tumor lesions used for newly acquired biopsies should not be target lesions, unless there are no other lesions suitable for biopsy, and in this instance only core needle (not excisional/incisional) biopsy is allowed. Samples with limited tumor content and fine needle aspirate specimens are not acceptable. The tumor specimen should be of sufficient quantity to allow for exploratory biomarker analyses and is preferred in formalin fixed paraffin embedded blocks.
• For a female of childbearing potential, have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required (Refer to Section 4.6.2).
• For a female of childbearing potential, be willing to use an adequate method of contraception as outlined in the protocol for the course of the study through 90 days after the last dose of study treatment.
• For a male subject with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception as outlined in the protocol, starting with the first dose of study therapy through 90 days after the last dose of study therapy. Males with pregnant partners must agree to use an adequate method according to the protocol (Refer to Section 4.6.2) no additional method of contraception is required for the pregnant partner.

You may not qualify if:

• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has exposed to vactosertib or imatinib for treatment purpose
• Before the first dose of trial treatment (\<2 weeks prior to first dose):
• Has received prior systemic cytotoxic chemotherapy
• Has received antineoplastic biological therapy
• Had major surgery \*Note: Subjects should recover from therapy related toxicity to less than CTCAE Grade 2 in order to participate in this trial.
• Is taking prohibited medications when using vactosertib as following (Refer to Appendix D Prohibited Concurrent Medications with Vactosertib (Ver 06Mar2020)
• A minimal washout period of 5 half-lives for the following drugs is mandatory prior to the first dosing.
• Concurrent use of drugs or foods that are known strong CYP3A4 inhibitors including but not limited to grapefruit juice, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, voriconazole. The topical use of these medications (if applicable), such as 2% ketoconazole cream, may be allowed.
• Concurrent use of drugs that are known potent CYP3A4 inducers including but not limited to phenytoin, rifampin, St. John's wort.
• Concurrent use of drugs that are CYP3A4, CYP1A2, CYP2B6 substrates with narrow therapeutic indices including but not limited to theophylline, astemizole, cisapride, cyclosporine, dihydroergotamine, ergotamine, sirolimus, tacrolimus, terfenadine (astemizole, cisapride, and terfenadine have been withdrawn from the US market).
• Concurrent use of drugs that are sensitive CYP3A4, CYP1A2, CYP2B6 substrates including but not limited to efavirenz, darunavir, dasatinib, everolimus, lopinavir, midazolam, sirolimus, ticagrelor.
• Has severe hypersensitivity to vactosertib, imatinib, and/or any of its excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.

Sponsors & Collaborators

• MedPacto, Inc.: lead

Study Sites (1)

Yeonsei University Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Dermoid Cyst

Interventions

vactosertib; Imatinib Mesylate

Condition Hierarchy (Ancestors)

Cysts; Neoplasms; Teratoma; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Sunjin Hwang, MD

  MedPacto, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1:1 allocation into two arms

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: January 23, 2024
• Study Start: June 1, 2021
• Primary Completion: May 23, 2022
• Study Completion: May 23, 2022
• Last Updated: December 9, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)