TAS-116 Plus Palbociclib in Breast and Rb-null Cancer

NCT05655598 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: BrUOG 387
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of TAS-116 with palbociclib in two groups of patients:

• Patients with advanced breast cancer that has become worse after taking palbociclib alone
• Patients with cancers that have an abnormality in a gene called the "retinoblastoma gene".

Conditions

Advanced Breast Cancer; Treatment-Refractory Solid Tumors; Retinoblastoma Deficiency; SCLC; Soft Tissue Sarcoma; Endometrial Cancer; Bladder Cancer

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of TAS-116 with palbociclib.

  Dose Limiting Toxicities (DLTs) will include grade 4 neutropenia lasting longer than 7 days, neutropenic fever, grade 4 thrombocytopenia or any Grade 3 non-hematologic toxicity not controlled with medical management.

  Start of study treatment through 90 days after last treatment.

Secondary Outcomes (1)

• Response rate

  2 months, 6 months, and 12 months of treatment

Study Arms (3)

Level 0 Starting Palbociclib with TAS-116

EXPERIMENTAL

Drug: Palbociclib Oral Product; Drug: TAS-116

Level -1 Palbociclib with TAS-116

EXPERIMENTAL

Drug: Palbociclib Oral Product; Drug: TAS-116

Level -2 Palbociclib with TAS-116

EXPERIMENTAL

Drug: Palbociclib Oral Product; Drug: TAS-116

Interventions

Palbociclib Oral Product DRUG

125 mg/day (FDA approved dose) or the last tolerated dose before progression for 21 days of a 28-day cycle

Level -1 Palbociclib with TAS-116; Level -2 Palbociclib with TAS-116; Level 0 Starting Palbociclib with TAS-116

TAS-116 DRUG

120 mg/day, 5 days on 2 days off, for days 1-28 of a 28 day cycle

Level 0 Starting Palbociclib with TAS-116

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed solid tumors such as ER/PR(+), HER2(-) breast cancer, SCLC, soft tissue sarcoma, endometrial cancer, bladder cancer that has progressed on at least one standard therapy or for which there is no standard therapy. (Metastases or recurrences do not need to be histologically confirmed.)
• Patients with breast cancer whose tumors progressed after prior palbociclib.
• Patients with any treatment-refractory solid tumor that is RB-deficient (9 patient cohort expansion after phase Ib dose de-escalation phase). Examples include SCLC, soft tissue sarcoma, endometrial cancer, bladder cancer. Patients should have no available standard therapy.
• Patients must have at least one area of measurable disease per RECIST Version 1.1 for solid tumors.
• Recovered (\< grade 1) from clinically significant effects of any prior surgery, radiotherapy or other anti-neoplastic therapy, except alopecia
• Males or females age \>18 years
• Life expectancy \> 60 days as documented by treating investigator
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1
• Patients must have normal organ and marrow function as defined in detail in the study protocol
• Women must not pregnant and not nursing.
• Women of childbearing potential must have a negative pregnancy test (urine or serum) within 7 days prior to starting the study drug (prior to Day 1 of treatment). Both males and females must agree to use effective birth control during the study (prior to the first dose and for 7 months after the last dose for females and 4 months after the last dose for males) if conception is possible during this interval. Female patients are considered to not be of childbearing potential if they have a history of hysterectomy or are post-menopausal defined as no menses for 12 months without an alternative medical cause
• Post-menopausal women (surgical menopause or lack of menses \>12 months) do not need to have a pregnancy test, please document status. (Female patients are considered to not be of childbearing potential if they have a history of hysterectomy or are post-menopausal defined as no menses for 12 months without an alternative medical cause.).
• Patient must be able to swallow capsules and retain orally administered medication and not have any clinically significant gastrointestinal abnormalities that may alter absorption, such as malabsorption syndrome or major resection of the stomach or bowels.
• Patients must be able to understand and willing to sign a written informed consent document and to comply with the protocol.
• Women of childbearing potential enrolled in this study must agree to use adequate barrier birth control measures during the course of the study and for at least 7 months after the last dose on study.

You may not qualify if:

• Pregnant or breastfeeding women are excluded from this study.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or TAS-116.
• Patients receiving any medications or substances that are substrates, inducers, or inhibitors of the CYP3A enzyme.
• Patients with a history of primary central nervous system tumors or brain metastases or who have signs/symptoms attributable to brain metastases and have not been assessed with radiologic imaging to rule out the presence of brain metastases.
• Patients may not be receiving any other investigational agents or anti-cancer therapies.
• Patients who have a history of another primary malignancy, with the exception of locally excised nonmelanoma skin cancer and carcinoma in situ of uterine cervix. A patient who has had no evidence of disease from another primary cancer for 3 or more years is allowed to participate in the study.
• Patients with known history of hepatitis C or chronic active hepatitis B.
• Patients with known diagnosis of human immunodeficiency virus (HIV) infection.
• Any significant ophthalmologic abnormality
• Any other condition that may increase the risk of corneal epithelial damage
• Corrected visual acuity \< 0.5 (using the international visual acuity measurement standard)
• Patients who have any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the Investigator and sponsor, could affect the patient's participation in the study such as:
• Uncontrolled diabetes mellitus.
• Nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by treatment with this study treatment.
• Liver disease such as decompensated liver disease, chronic active hepatitis, or chronic persistent disorders.

Sponsors & Collaborators

• Brown University: lead

Study Sites (1)

Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

Location

MeSH Terms

Conditions

Sarcoma; Endometrial Neoplasms; Urinary Bladder Neoplasms

Interventions

TAS-116

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Wafik El-Deiry, MD, PhD, FACP

  Brown University & Lifespan Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2022
• First Posted: December 19, 2022
• Study Start: September 12, 2023
• Primary Completion: August 5, 2024
• Study Completion: August 5, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)