Clinical Trials /

Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy

NCT03201913

Description:

Phase1 study of TTC 352 for treatment of metastatic ER+ breast cancer.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy
  • Official Title: Phase 1 Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy

Clinical Trial IDs

  • ORG STUDY ID: TTC-352-101
  • NCT ID: NCT03201913

Conditions

  • Metastatic ER+ Breast Cancer

Interventions

DrugSynonymsArms
TTC-352Accelerated dose escalation study

Purpose

Phase1 study of TTC 352 for treatment of metastatic ER+ breast cancer.

Detailed Description

      This is open-label, accelerated dose escalation study of TTC 352, a selective human ER
      partial agonist for treatment of metastatic ER+ breast cancer in patients who received and
      progressed on at least two lines of endocrine therapy with one that included a CDK4/CDK6
      inhibitor.

      The primary objective of this study is to determine the maximum tolerated dose (MTD) of
      TTC-352 for the treatment of metastatic ER+ breast cancer progressing after endocrine
      therapy.

      The maximum tolerated dose (MTD) of TTC-352 will be determined using initial single-patient
      cohort escalations until grade 2 toxicity, then expansion to a modified-Fibonacci
      dose-escalation 3+3 design. Patients enrolled at each dose escalation step must complete the
      first 28-day cycle of treatment without a dose-limiting toxicity (DLT), or be withdrawn
      because of a DLT, before additional patients may be enrolled for the next dose escalation
      step. The MTD dose level cohort will be expanded to a total of 9 patients, to further
      evaluate safety. In each cohort pharmacokinetics of TTC-352 will be evaluated.
    

Trial Arms

NameTypeDescriptionInterventions
Accelerated dose escalation studyExperimentalDose escalation of TTC-352 administered as an oral capsule, twice a day for 28 days (one cycle). Patients will receive sequential 28-day cycles of treatment until disease progression, unacceptable toxicity, patient refusal to continue treatment, any other reason to discontinue treatment (e.g., further participation is not in the patient's best interest) or study completion/termination.
  • TTC-352

Eligibility Criteria

        Inclusion Criteria:

          1. be ≥18 years of age;

          2. have a diagnosis of metastatic ER+ breast cancer in patients who received and
             progressed on at least two lines of endocrine therapy, with one that included a
             CDK4/CDK6 inhibitor (e.g., palbociclib or ribociclib);

          3. have metastatic disease evaluable on imaging studies;

          4. have a histologically confirmed diagnosis of ER+ breast cancer;

          5. have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 (Appendix
             II);

          6. have adequate hepatic function, defined as having a serum total bilirubin
             concentration ≤1.5mg/d, or ≤2 x the upper limit of normal (ULN) if associated with
             hepatobiliary metastases or Gilbert syndrome, and having serum aspartate
             aminotransferase (AST) and alanine aminotransferase (ALT) concentrations ≤2.5 × ULN,
             or ≤5 x ULN for patients with known hepatic metastases;

          7. have adequate renal function, defined as having a serum creatinine ≤1.5 × ULN and a
             creatinine clearance ≥40mL/min (estimated using the Cockcroft-Gault formula);

          8. have adequate hematologic function, defined as having a hemoglobin ≥8g/dL, an absolute
             neutrophil count (ANC) ≥1.0 × 109/L, and platelet count ≥75.0 x 109/L;

          9. be willing and able to comply with study visits and procedures;

         10. have read, understood and signed the informed consent form (ICF) approved by the
             Institutional Review Board (IRB);

         11. if a woman of childbearing potential (WOCP), not be pregnant (confirmed by a negative
             serum pregnancy test within 14 days of study entry and re-confirmed by a urine
             pregnancy test on the morning of Study Day 1, prior to the start of study treatment)
             and/or not be breast-feeding; [Note: Women who are postmenopausal for at least 1 year
             or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or
             hysterectomy) are not considered to be a WOCP.]

         12. If a WOCP, agree to use during the study and for at least one month after the last
             dose of study drug a medically acceptable method of birth control [such as an oral,
             implantable, injectable, or transdermal hormonal contraceptive, an intrauterine device
             (IUD), a double barrier method (condoms, sponge, diaphragm, or vaginal ring with
             spermicidal jellies or cream), or total abstinence.];

         13. if male (and whether or not surgically or medically sterile), agree to use during the
             study and for at least one month after the last dose of study drug a double barrier
             method of birth control (in addition to any other birth control method practiced by
             his partner) while engaging in sexual intercourse with a partner who is pregnant,
             possibly pregnant or able to become pregnant.

        Exclusion Criteria:

          1. have received chemotherapy, hormonal therapy, biologic therapy, immunotherapy or
             radiation therapy within 14 days prior to the planned start of study treatment.

          2. have inadequate recovery* from adverse events resulting from previously-administered
             anti-cancer therapies; [*Note: Unless more specifically defined in Inclusion Criteria
             6, 7 and 8 above, adequate recovery is defined as improvement to ≤ Grade 2 for any
             other hematologic toxicity and for peripheral neuropathy, and improvement to ≤ Grade 1
             for any other non-hematologic toxicity.]

          3. have a history of venous thromboembolism, including deep vein thrombosis, pulmonary
             embolism or retinal vein thrombosis, unless currently on anticoagulant therapy;

          4. have impending visceral crisis that requires chemotherapy;

          5. have known uncontrolled or symptomatic CNS metastases;

          6. have any clinically significant infection, defined as any acute viral, bacterial, or
             fungal infection that requires systemic treatment or have received any anti-infective
             treatment within 7 days prior to the screening visit;

          7. have any other severe, uncontrolled medical condition, including unstable congestive
             heart failure (Stage III-IV of the New York Heart Association Functional
             Classification (Appendix III))

          8. have a known or suspected allergy to the study drug or any study drug component;

          9. have any other medical or psychiatric condition or laboratory abnormality that may
             increase the risk associated with study participation, that may interfere with the
             interpretation of study results or that otherwise would, in the opinion of the
             Investigator, make study participation inappropriate;

         10. have any non-healing wound, fracture, or ulcer within 28 days prior to the planned
             start of study treatment;

         11. have received any other investigational drug within 28 days (or 5 half-lives, if
             longer) prior to the start of study screening.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD
Time Frame:24 months
Safety Issue:
Description:The primary objective of this study is to determine the maximum tolerated dose (MTD) of TTC-352 for the treatment of metastatic ER+ breast cancer progressing after endocrine therapy

Secondary Outcome Measures

Measure:Best response to treatment
Time Frame:24 months
Safety Issue:
Description:Determine patient best response to treatment (complete response, partial response, stable disease or disease progression) after at least two 28-day cycles of treatment with TTC 352.
Measure:PFS
Time Frame:24 months
Safety Issue:
Description:Determine durations of progression-free survival after at least two 28-day cycles of treatment with TTC 352
Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame:24 months
Safety Issue:
Description:Treatment-related adverse events as assessed by CTCAE v4.0 will be collected in presented in tabular form at the end of study.
Measure:Maximum Plasma Concentration (Cmax)
Time Frame:24 months
Safety Issue:
Description:Blood samples will be collected at the following Cycle 1 time points: Day 1: prior to dosing and at Hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 and 24 after dosing (just before dosing on Day 2). Day 28: prior to dosing and at Hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 28 after dosing. TTC-352 blood levels will be measured at above time points and Cmax will be calculated.
Measure:Half life
Time Frame:24 months
Safety Issue:
Description:Blood samples will be collected at the following Cycle 1 time points: Day 1: prior to dosing and at Hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 and 24 after dosing (just before dosing on Day 2). Day 28: prior to dosing and at Hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 28 after dosing. TTC-352 blood levels will be measured at above time points and half life of TTC-352 will be calculated.
Measure:Area Under the Curve (AUC)
Time Frame:24 months
Safety Issue:
Description:Blood samples will be collected at the following Cycle 1 time points: Day 1: prior to dosing and at Hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12 and 24 after dosing (just before dosing on Day 2). Day 28: prior to dosing and at Hours 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 12, 24 and 28 after dosing. TTC-352 blood levels will be measured at above time points and AUC will be calculated.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:TTC Oncology, LLC

Last Updated

October 11, 2017