Study of TAK-228 In Patients With Previously Treated Metastatic Renal Cell Carcinoma

NCT03097328 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 16-527
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 8

Brief Summary

This research study is investigating a drug as a possible treatment for metastatic renal cell carcinoma. The intervention involved in this study is TAK-228.

Conditions

Renal Cell Carcinoma

Keywords

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate

  The best overall response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1). CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.

  Imaging assessments occurred every eight weeks (2 cycles) for response evaluation. The median number of cycles administered was 2 (range <1-15), thus participants were assessed up to ~14 months.

Secondary Outcomes (3)

• Median Progression Free Survival

  Participants followed for up to 14 months

• Median Overall Survival

  Participants were follow for up to ~27 months

• Percentage of Participants With Any Grade 3 or Higher Treatment-related Adverse Events

  Adverse events are measured continuously on treatment and up to thirty days after going off treatment (up to ~15 months).

Study Arms (1)

TAK-228

EXPERIMENTAL

* TAK-228 will be taken orally on a weekly basis for 4 weeks per cycle * Dosage will be determined by the study team

Drug: TAK-228

Interventions

TAK-228 DRUG

TAK-228 works to inhibit or interfere with cellular functions involved in cell growth and survival. TAK-228 specifically targets a type of protein that can make chemicals that trigger cell growth, including cancer cell growth

Also known as: INK128

TAK-228

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.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• Documented pathologic diagnosis of RCC. All subtypes eligible including but not limited to clear cell, papillary, chromophobe, collecting duct carcinoma, medullary carcinoma, and unclassified categories. Sarcomatoid and rhabdoid differentiation are allowed.
• Patients with clear cell histology must have demonstrated: 1) Progression on at least one prior anti -angiogenic agent unless intolerable; AND 2) progression on at least one agent that blocks the PD-1 pathway unless felt by the treating physician to be contraindicated (examples include but are not limited to: patients with autoimmune disease or patients requiring systemic steroids greater than 10 mg/day prednisone or its equivalent) or if they have been discontinued due to toxicity. Prior rapalogues are allowed.
• Patients with non-clear cell histology must have received at least one prior anti-cancer therapy. Prior rapalogues are allowed.
• Left ventricular ejection fraction (LVEF) ³ lower limit of normal (LLN) as assessed by either multigated acquisition (MUGA) scan or echocardiogram (ECHO).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Must have adequate organ and bone marrow function.
• Hematological
• Absolute Neutrophil Count (ANC) ≥ 1500 K/mm\^3 (without use of G-CSF 4 weeks prior to enrollment)
• Hemoglobin (Hgb) ≥ 9 g/dL (transfusions allowed)
• Platelets (Plts) ≥ 100 k/mm\^3
• Renal
• Calculated creatinine clearance (Cockcroft-Gault formula will be used to calculate creatinine clearance) ≥ 30 mL/min
• Urinalysis: For patients with 2+ proteinuria on urinalysis, 24 hour urine collection should be obtained, 24 hour urine protein should be \<2 grams.

You may not qualify if:

• Subjects with a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 6 months of study treatment initiation.
• Receipt of any type of small molecular kinase inhibitor (including investigational kinase inhibitors) within 2 weeks of enrollment or receipt of any anti-cancer therapy (including investigational therapy, monoclonal antibodies, cytokine therapy) within 3 weeks of enrollment.
• Treatment with any investigational products within 3 weeks before the first dose of study drug.
• Radiation therapy for bone metastases within 2 weeks, other external radiation therapy within 4 weeks of enrollment.
• Received prior hemibody external radiotherapy.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy, radiosurgery, or surgery and stable for at least 4 weeks prior to enrollment as documented by magnetic resonance imaging (MRI) or computed tomography (CT) imaging. Treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 4 weeks prior to enrollment as documented by MRI or CT imaging.
• Imminent or established spinal cord compression based on clinical and/or imaging. In subjects with untreated imminent or established spinal cord compression, treatment with standard of care as clinically indicated should be completed at least 4 weeks before enrollment.
• The subject has a 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
• Significant active cardiovascular or pulmonary disease including:
• Uncontrolled hypertension defined as sustained BP \>160 mm Hg systolic or \> 95 mm Hg diastolic despite optimal antihypertensive treatment.

Sponsors & Collaborators

• Bradley A. McGregor, MD: lead
• Calithera Biosciences, Inc: collaborator

Study Sites (8)

University of California, San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02215, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (1)

• McGregor BA, Xie W, Adib E, Stadler WM, Zakharia Y, Alva A, Michaelson MD, Gupta S, Lam ET, Farah S, Nassar AH, Wei XX, Kilbridge KL, Harshman L, Signoretti S, Sholl L, Kwiatkowski DJ, McKay RR, Choueiri TK. Biomarker-Based Phase II Study of Sapanisertib (TAK-228): An mTORC1/2 Inhibitor in Patients With Refractory Metastatic Renal Cell Carcinoma. JCO Precis Oncol. 2022 Feb;6:e2100448. doi: 10.1200/PO.21.00448.

  PMID: 35171658 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

sapanisertib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Bradley McGregor, MD
• Organization: Dana Farber Cancer Institute

Bradley_McGregor@DFCI.harvard.edu

617-632-6328

Study Officials

• Bradley McGregor, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 15, 2017
• First Posted: March 31, 2017
• Study Start: August 1, 2017
• Primary Completion: July 20, 2021
• Study Completion: April 24, 2024
• Last Updated: April 29, 2024
• Results First Posted: February 24, 2022

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)