Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Nivolumab

Atezolizumab

Taxane

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Tesetaxel

Nivolumab at 360 mg by intravenous infusion Q3W

Pembrolizumab at 200 mg by intravenous infusion Q3W

Atezolizumab at 1,200 mg by intravenous infusion Q3W

Joseph O'Connell, M.D.

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with metastatic breast cancer (MBC). In Cohort 1, approximately 200 patients with triple-negative MBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel plus either: (1) nivolumab; (2) pembrolizumab; or (3) atezolizumab. The primary efficacy endpoints for Cohort 1 are objective response rate (ORR) and progression free survival (PFS) in patients with programmed death-ligand 1 (PD-L1) positive status. In Cohort 2, approximately 60 elderly patients with human epidermal growth factor receptor 2 (HER2) negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy. The primary efficacy endpoints for Cohort 2 are ORR and PFS in patients with hormone receptor (HR)-positive, HER2-negative disease. In Cohort 3, approximately 60 non-elderly adult patients with HER2-negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy. The primary efficacy endpoints for Cohort 3 are ORR and PFS in patients with HR positive, HER2-negative disease.

CONTESSA TRIO is a multi-cohort, multicenter, Phase 2 study of tesetaxel, an investigational, orally administered taxane, in patients with MBC.

Cohort 1:

Approximately 200 patients with triple-negative MBC who have not received prior chemotherapy for advanced disease will be randomized 1:1:1 to receive tesetaxel dosed orally at 27 mg/m2 once every three weeks (Q3W) plus either:

* Nivolumab at 360 mg by intravenous infusion Q3W;
* Pembrolizumab at 200 mg by intravenous infusion Q3W; or
* Atezolizumab at 1,200 mg by intravenous infusion Q3W.

Nivolumab and pembrolizumab (programmed cell death protein 1 \[PD-1\] inhibitors) and atezolizumab (a programmed death-ligand 1 \[PD-L1\] inhibitor) are immuno-oncology (IO) agents approved for the treatment of multiple types of cancer. Two of these agents, atezolizumab and pembrolizumab, have been approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for patients with triple-negative MBC. The primary efficacy endpoints for Cohort 1 are ORR and PFS in patients with PD-L1 positive status. The secondary efficacy endpoints are ORR and PFS in all patients, duration of response (DoR) and overall survival (OS).

Cohort 2:

Approximately 60 elderly patients with HER2-negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy dosed orally at 27 mg/m2 Q3W. The primary efficacy endpoints for Cohort 2 are ORR and PFS in patients with HR-positive, HER2-negative disease. The secondary efficacy endpoints are ORR and PFS in patients with triple-negative disease, DoR and OS.

Cohort 3:

Approximately 60 non-elderly adult patients with HER2-negative MBC who have not received prior chemotherapy for advanced disease will receive tesetaxel monotherapy dosed orally at 27 mg/m2 Q3W. The primary efficacy endpoints for Cohort 3 are ORR and PFS in patients with HR positive, HER2-negative disease. The secondary efficacy endpoints are ORR and PFS in patients with triple negative disease, DoR and OS.

Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC

A Multicenter, Phase 2 Study of Tesetaxel Plus Three Different PD-(L)1 Inhibitors in Patients With Triple-Negative, Locally Advanced or Metastatic Breast Cancer and Tesetaxel Monotherapy in Elderly and Non-Elderly Adult Patients With HER2-Negative, Locally Advanced or Metastatic Breast Cancer

Odonate Therapeutics, Inc.

Nervous System Diseases

Neoplasms, Second Primary

Brain Neoplasms

Neoplastic Processes

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Temozolomide

Topotecan

Antineoplastic Agents, Alkylating

Alkylating Agents

Topoisomerase I Inhibitors

Enzyme Inhibitors

Temozolomide pills are to be taken on an empty stomach at night and should not be chewed. Patients receive Temozolomide on days 1-5 of a 28-day schedule. Patients will receive Topotecan intravenous treatment days 2-6 of each 28-day cycle at The Mehthodist Hospital Outpatient Infusion Center.

Patients will receive Topotecan intravenous treatment days 2-6 of each 28-day cycle at The Mehthodist Hospital Outpatient Infusion Center.

Temozolomide is taken on an empty stomach at night and should not be chewed. Patients receive Temozolomide on days 1-5 of a 28-day schedule.

Pamela Z New, M.D.

The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with Temozolomide and Topotecan in patients with CNS metastases of solid tumors. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years and will receive 8 cycles of chemotherapy. The primary endpoint is the determinant median overall survival and progression-free survival of this regimen, time to progression of the brain metastases, and assessment of toxicity levels in this regimen.

The long-term objective of this research project is to develop chemotherapy-based approach to the treatment of brain metastases. The specific purpose of this study is to obtain data on safety and efficacy of combination chemotherapy with temozolomide and topotecan in patients with central nervous system (CNS) metastases of solid tumors. Patients with brain metastases of solid tumors have a poor prognosis, despite improvements in survival achieved with modern neurosurgical and radiation techniques. Chemotherapy does not play any significant role in this disease, but may have application in salvage of patients who have failed radiation therapy. In patients who are not surgical candidates, do not require immediate XRT to relieve symptoms and have controlled systemic disease, effective chemotherapy as an alternative to XRT might decrease the risk of radiation induced neurotoxicity.

Recent advances in treatment of systemic disease with the use of modern chemotherapy and pathobiologic agents have significantly improved overall survival of cancer patients, putting them at risk for CNS metastases and radiation induced neurotoxicity. Both, temozolomide and topotecan have good blood-brain barrier penetration and have shown activity in CNS malignancies. Preclinical studies suggest synergy of this drug combination. This is a single-arm, open-label phase II drug study. All patients will receive the chemotherapy combination. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years. Patients will receive up to 8 cycles of chemotherapy. The primary endpoint is the rate of radiologic response of brain metastases and secondary endpoints are median overall survival, progression-free survival, time to progression of brain metastases and toxicity. The study is expected to provide data to be used in generating further research hypotheses.

Phase II Trial of Chemotherapy With Temodar With Topotecan for CNS Metastasis of Solid Tumors

Phase II Trial of Chemotherapy With Temozolomide in Combination With Topotecan for Central Nervous System (CNS) Metastasis of Solid Tumors

The primary objective of this study is to determine the overall rate of radiologic response of brain metastases to combination chemotherapy with temozolomide and topotecan in patients with CNS metastases of solid tumors

Secondary objectives are to determine median overall survival and progression-free survival on this regimen, to determine time to progression of the brain metastases, and to assess toxicity of this regimen

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC	NCT03952325	Breast Cancer	Tesetaxel Tesetaxel Tesetaxel Nivolumab Pembrolizumab Atezolizumab Tesetaxel	18 Years -	Odonate Therapeutics, Inc.
Phase II Trial of Chemotherapy With Temodar With Topotecan for CNS Metastasis of Solid Tumors	NCT01736800	Central Nervous... Brain Metastase...	Topotecan Temozolomide	18 Years - 79 Years	The Methodist Hospital Research Institute
Tesetaxel Plus 3 Different PD-(L)1 Inhibitors in Patients With Triple-Negative MBC and Tesetaxel Monotherapy in Patients With HER2-Negative MBC	NCT03952325	Breast Cancer	Tesetaxel Tesetaxel Tesetaxel Nivolumab Pembrolizumab Atezolizumab Tesetaxel	18 Years -	Odonate Therapeutics, Inc.

Spots Global Cancer Trial Database for central nervous system (cns) metastases