Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Fulvestrant

Estrogens

Aromatase Inhibitors

Patients will get LSZ102 single agent during dose escalation.

Patients will get LSZ102 in combination with LEE011 during dose escalation.

Patients will get LSZ102 in combination with BYL719 during dose escalation.

Patients will get LSZ102 single agent during dose expansion

Patients will get LSZ102 + LEE011 (LEE011 intermittent regimen) during dose expansion

Patients will get LSZ102 + LEE011 (LEE011 continuous regimen) during dose expansion

Patient will get LSZ102 in combination with BYL719 during dose expansion

LSZ102

LEE011

BYL719

Novartis Pharmaceuticals

To characterize the safety and tolerability, identify recommended doses and regimens for future studies, pharmacokinetics (PK), pharmacodynamics (PD) and anti-tumor activity of LSZ102 as a single agent and in combination with either LEE011 or BYL719 in adult patients with locally advanced or metastatic ER+ breast cancer who have progressed after endocrine therapy.

Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers

A Phase I/Ib, Open Label Study of LSZ102 Single Agent and LSZ102 in Combination With Either LEE011 (LSZ102 + LEE011) or BYL719 (LSZ102 + BYL719) in Patients With Advanced or Metastatic ER+ Breast Cancer Who Have Progressed After Endocrine Therapy

The dose escalation part of the study will be guided by well-established statistical methods/models to estimate the maximum tolerated doses (MTD)and/or recommended doses for expansion (RDE). Safety, pharmacokinetic and pharmacodynamics data will guide dose escalation decisions.

Incidence and severity of adverse events, serious adverse events, clinical laboratory values, vital signs, ECGs, dose interruptions, dose reductions and dose intensity.

Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719. ORR is defined as the proportion of patients with a best overall response of complete response or partial response.

Assessment of preliminary anti-tumor activity of LSZ102, LSZ102 + LEE011 and LSZ102 + BYL719

Plasma concentration versus time under fasted and fed conditions

Cmax = Maximum observed plasma concentration after drug administration

Cmin = Minimum observed plasma concentration after drug administration

Hormones

Hormone Antagonists

Dose 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.

Phase 1 study to determine the maximum tolerated dose (MTD) of TTC-352.

TTC-352

Arkadiusz Z Dudek, MD

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

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.

Open-label, accelerated dose escalation study.

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

Phase 1 Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy

At present TTC Oncology does not plan to share IPD with other researchers.

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

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.

Determine durations of progression-free survival after at least two 28-day cycles of treatment with TTC 352

Treatment-related adverse events as assessed by CTCAE v4.0 will be collected in presented in tabular form at the end of study.

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.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I/Ib Trial of LSZ102 Single Agent or LSZ102 + LEE011 or LSZ102 + BYL719 in ER+ Breast Cancers	NCT02734615	Advanced or Met...	LSZ102 LEE011 BYL719	18 Years -	Novartis
Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy	NCT03201913	Metastatic ER+ ...	TTC-352	18 Years -	TTC Oncology, LLC
Study of TTC-352 in Patients With Metastatic Breast Cancer Progressing on Endocrine Therapy	NCT03201913	Metastatic ER+ ...	TTC-352	18 Years -	TTC Oncology, LLC

Spots Global Cancer Trial Database for metastatic er+ breast cancer