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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05655598
Recruitment Status : Recruiting
First Posted : December 19, 2022
Last Update Posted : September 14, 2023
Sponsor:
Information provided by (Responsible Party):
Brown University

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".

Condition or disease Intervention/treatment Phase
Advanced Breast Cancer Treatment-Refractory Solid Tumors Retinoblastoma Deficiency SCLC Soft Tissue Sarcoma Endometrial Cancer Bladder Cancer Drug: Palbociclib Oral Product Drug: TAS-116 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 27 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib IIT of Heat Shock Protein 90 Inhibitor TAS-116 Combined With Cyclin-dependent Kinase 4/6 Inhibitor Palbociclib in Advanced Breast Cancer Progressing on Palbociclib & Treatment-refractory Solid Tumors With Retinoblastoma Deficiency
Actual Study Start Date : September 12, 2023
Estimated Primary Completion Date : August 2024
Estimated Study Completion Date : August 2025


Arm Intervention/treatment
Experimental: Level 0 Starting Palbociclib with TAS-116 Drug: Palbociclib Oral Product
125 mg/day (FDA approved dose) or the last tolerated dose before progression for 21 days of a 28-day cycle

Drug: TAS-116
120 mg/day, 5 days on 2 days off, for days 1-28 of a 28 day cycle

Experimental: Level -1 Palbociclib with TAS-116 Drug: Palbociclib Oral Product
125 mg/day (FDA approved dose) or the last tolerated dose before progression for 21 days of a 28-day cycle

Drug: TAS-116
80 mg/day, 5 days on 2 days off, for days 1-28 of a 28 day cycle

Experimental: Level -2 Palbociclib with TAS-116 Drug: Palbociclib Oral Product
125 mg/day (FDA approved dose) or the last tolerated dose before progression for 21 days of a 28-day cycle

Drug: TAS-116
40 mg/day, 5 days on 2 days off, for days 1-28 of a 28 day cycle




Primary Outcome Measures :
  1. Safety and tolerability of TAS-116 with palbociclib. [ Time Frame: Start of study treatment through 90 days after last treatment. ]
    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.


Secondary Outcome Measures :
  1. Response rate [ Time Frame: 2 months, 6 months, and 12 months of treatment ]
    Complete response (CR), partial response (PR), stable disease (SD) at RP2D will be estimated according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Men enrolled in this study must agree to use adequate barrier birth control measures during the course of the study and for at least 4 months after the last treatment on study.
  • In addition to alopecia and stable peripheral neurotoxicity below grade 2, any clinical toxicity associated with previous treatment prior to enrollment must be restored to baseline or grade 1.

Exclusion Criteria:

  • 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 with treated brain metastases that are asymptomatic and have been clinically stable for at least 4 weeks will be eligible. Medical condition exclusions
  • 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.
  • Autoimmune and ischemic disorders (>=Grade 2).
  • Ongoing or active infection symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia within 6 months of registration, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Significant gastrointestinal abnormalities, including active ulcerative colitis, chronic diarrhea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous alimentation.
  • Patients with any comorbid medical disorder that, in the opinion of the Investigator or sponsor, may increase the risk of toxicity.
  • Patients who have a history of noninfectious (toxic, autoimmune) hepatitis or alcoholism.
  • Patients with a lifetime history of porphyria or psoriasis.
  • Patients with documented glucose-6-phosphate dehydrogenase deficiency.
  • Patients with a history of seizure disorder (except infant febrile seizures).
  • Patients with a lifetime history of dermatitis as an allergic/toxic reaction to any medication.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Impaired pulmonary function, history of interstitial lung disease (ILD) and/or pneumonitis.
  • Weight loss of >10% in the past month.Organ function and laboratory values exclusion
  • Patients who have impaired cardiac function or clinically significant cardiac disease
  • Chemotherapy, biologic therapy, targeted therapy, immunotherapy, radiotherapy, or investigational agents within 5 half-lives or within 4 weeks (whichever is shorter) prior to administration of first dose of study drug on Day 1 or have not recovered from the side effects of such therapy
  • Prior treatment with HSP90 inhibitor.
  • Major surgery/surgical therapy for any cause within 4 weeks of screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05655598


Contacts
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Contact: Brown University Oncology Research Group 401-863-3000 BrUOG@brown.edu

Locations
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United States, Rhode Island
Lifespan Cancer Institute Recruiting
Providence, Rhode Island, United States, 02903
Contact    844-222-2881      
Sponsors and Collaborators
Brown University
Investigators
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Principal Investigator: Wafik El-Deiry, MD, PhD, FACP Brown University & Lifespan Cancer Institute
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Responsible Party: Brown University
ClinicalTrials.gov Identifier: NCT05655598    
Other Study ID Numbers: BrUOG 387
First Posted: December 19, 2022    Key Record Dates
Last Update Posted: September 14, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Sarcoma
Endometrial Neoplasms
Retinoblastoma
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Urogenital Neoplasms
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Uterine Neoplasms
Genital Neoplasms, Female
Uterine Diseases
Genital Diseases, Female
Genital Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Retinal Neoplasms
Eye Neoplasms
Eye Diseases, Hereditary
Eye Diseases
Retinal Diseases
Palbociclib