Study of TAK-228 (MLN0128) in Soft Tissue Sarcomas

NCT02987959 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: SAR-081
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label phase II study of TAK-228 for patients ≥ 18 years of age with complex genomic sarcomas exhibiting Phosphoinositide-3 Kinase (PI3K) pathway dysregulation. Patients must have surgically unresectable or metastatic disease that is refractory to at least one prior line of therapy (not including neoadjuvant or adjuvant therapy in a curative setting). Patients disease must also have evidence of progression prior to enrollment. The purpose of this study is to determine the antitumor activity in this group of patients. Patients must meet all eligibility criteria as detailed in section 10. A total of up to 33 patients will be included in the study. Patients will undergo screening evaluations to determine eligibility within 28 days of the first dose. All patients will be required to submit baseline tumor samples for analysis. Patients who have had their tumors tested commercially for PI3K/ AKT/mechanistic Target of Rapamycin (mTOR) alterations will be assessed on a case by case basis for eligibility and for determination as to whether additional tissue is required. TAK-228 will be administered orally at 3 mg daily for a 21 day cycle. Clinical and laboratory assessments will be made on day 1 of each cycle. Disease will be assessed by comparing unidimensional tumor measurements on pre and peritreatment imaging (CT or MRI) after weeks 6, 12, 18 and every 12 weeks thereafter. Response will be assessed according to RECIST 1.1. Therapy will continue until disease progression or unacceptable toxicity or withdrawal of consent.

Conditions

Soft-tissue Sarcoma

Keywords

TAK-228; MLN0128; mTOR

Outcome Measures

Primary Outcomes (1)

• The Progression Free Survival Rate With TAK-228 in Sarcoma Patients With PI3K/AKT/mTOR Pathway Dysregulation

  Progression free rate will be determined by determining the number of patients with complete response, partial response and stable disease

  12 weeks post-treatment

Secondary Outcomes (4)

• The Rate of Toxicity of TAK-228 in This Patient Population as Per Common Terminology Criteria for Adverse Events (CTCAE)v4.03 Criteria.

  1 year

• The Objective Response Rate (ORR) of TAK-228 in This Patient Population.

  upto 4 years

• Progression Free Survival in This Patient Population.

  upto 4 years

• Overall Survival Rate in This Patient Population

  upto 4 years

Study Arms (1)

TAK-228 treatment

EXPERIMENTAL

Patients with complex genomic sarcomas exhibiting PI3K pathway dysregulation will be treated with TAK-228

Drug: TAK-228

Interventions

TAK-228 DRUG

TAK-228 is a novel, highly selective, orally bioavailable adenosine 5' triphosphate (ATP)-competitive inhibitor of the serine/threonine kinase referred to as the mechanistic target of rapamycin (mTOR). TAK-228 (formerly INK128) targets 2 distinct mTOR complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).

Also known as: MLN0128

TAK-228 treatment

Eligibility Criteria

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

You may qualify if:

• Male or female patients 18 years or older.
• Patients must have a diagnosis of a locally advanced or metastatic sarcoma that is progressing. The following subtypes (considered genomically complex) will be eligible: leiomyosarcoma (well differentiated or poorly differentiated), undifferentiated pleomorphic sarcoma, myxofibrosarcoma, pleomorphic rhabdomyosarcoma, pleomorphic liposarcoma, malignant peripheral nerve sheath tumor, angiosarcoma or extraskeletal osteosarcoma. Other potentially genomically complex Soft Tissue Sarcomas (STS) subtypes may be included on a case-by-case basis after discussion with the principal investigator.
• Measurable disease by RECIST 1.1 criteria (at least one target lesion outside of previous radiation fields or progressed within a previous radiation field), described in detail in section 15.
• Progression of disease by radiographic imaging (10% increase in size by RECIST v1.1 within 6 months of registration) or presence of new lesions.
• Must have received at least 1 prior systemic therapy for advanced disease (does not include adjuvant/neoadjuvant therapy in a curative setting).
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Adequate contraception as follows:
• For women:
• Postmenopausal for at least 1 year before the screening visit, OR Surgically sterile, OR If they are of childbearing potential, agree to practice 1 effective method of contraception, and 1 additional (barrier) method, at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling \[eg. United Surgical Partners Internationals (USPI), Summary of Product Characteristics (SmPC), etc;\]) after the last dose of study drug OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (Periodic abstinence \[e.g, calendar, ovulation, symptothermal, postovulation methods\] and withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
• Highly effective methods:
• Intra-uterine devices (IUD) Hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants)
• Other effective Methods:
• Latex Condoms Diaphragm with spermicide; Cervical cap;Sponge
• For men, even if surgically sterilized (ie, status post-vasectomy), they must:
• Agree to practice highly effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug, OR agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the patient (Periodic abstinence \[e.g, calendar, ovulation, symptothermal, postovulation methods for the female partner\] and withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

You may not qualify if:

• \. Tumor must have dysregulation of the PI3K/AKT/mTOR pathway. For the purposes of this study, patients must have either PTEN protein or genomic loss, or phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA)/ Phosphatase and tensin homolog (PTEN) mutation. Patients must be willing to provide sufficient archival tissue. If this is not available fresh tumor for biopsy is required. In the event that a patient has had tumor analyzed for PTEN/PIK3CA status through commercial means, their eligibility and need for additional tissue will be determined on a case by case basis by the principle investigator.
• Any clinically significant co-morbidities, such as uncontrolled pulmonary disease, active central nervous system disease, active infection, or any other condition that could compromise the patient's participation in the study.
• Known human immunodeficiency virus infection.
• Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
• Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug, or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Breast feeding or pregnant.
• Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of TAK-228. In addition, patients with enteric stomata are also excluded.
• Treatment with any investigational products, radiation therapy, surgery, tumor embolization, chemotherapy or immunotherapy within 21 days before the first dose of the study drug. For biologic or hormonal therapy treatment within 14 days or five half-lives of a drug (whichever is longer) before the first dose of study drug.
• History of any of the following within the last 6 months before administration of the first dose of the drug:
• Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures
• Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures
• Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation or ventricular tachycardia)
• Placement of a pacemaker for control of rhythm
• New York Heart Association (NYHA) Class III or IV heart failure

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Results Point of Contact

• Title: Protocol Developer
• Organization: Fox Chase Cancer Center

ryan.romasko@fccc.edu

215-728-4097

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2016
• First Posted: December 9, 2016
• Study Start: February 21, 2017
• Primary Completion: January 30, 2019
• Study Completion: July 24, 2020
• Last Updated: October 14, 2022
• Results First Posted: February 24, 2021

Record last verified: 2022-09

Locations

US (1)