A Phase II Study to Explore the Safety, Tolerability, and Preliminary Antitumor Activity of Sitravatinib Plus Tislelizumab or Combination With Nab-paclitaxel in Patients With Locally Recurrent or Metastatic Triple Negative Breast Cancer (TNBC) (SPARK)

November 17, 2023 updated by: Zhimin Shao, Fudan University
The purpose of this study is to assess the efficacy and safety of sitravatinib plus tislelizumab or combination with nab-paclitaxel in locally recurrent or metastatic triple-negative breast cancer (TNBC) patients.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a prospective, single-center, three cohorts, phase II clinical trial in locally recurrent or metastatic triple-negative breast cancer(TNBC) patients. Subjects will be divided into three cohorts by different treatment combination. Cohort A & Cohort B aim to explore the two dosages of sitravatinib in combination with tislelizumab in TNBC with prior ≤ 3 treatment line. Cohort A patients will receive 70mg sitravatinib (QD PO) in combination with 200mg tislelizumab (Q3W IV); Cohort B patients will receive 100mg sitravatinib (QD PO) in combination with 200mg tislelizumab (Q3W IV). Cohort C aims to explore the sitravatinib (QD PO) plus 200mg tislelizumab (Q3W IV) and 100 mg/m2 nab-paclitaxel (D1, D8 Q3W IV) in TNBC previously untreated for metastatic setting or recurred/metastasized after surgery. Subjects in the three cohorts will be treated until disease progression, intolerable toxicity, informed consent withdrawn, or investigators-determined medication termination. Drug efficacy and safety data will be collected.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
98

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

  • Name: Lei Fan, MD
  • Phone Number: 88603 86-021-64175590
  • Email: teddyfl@163.com

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
  • Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
  • Histologically confirmed diagnosis of TNBC characterized by estrogen-receptor negative (ER-), progesterone receptor negative (PR-) and human epidermal growth factor-2 receptor negative (HER2-);
  • ≤ 3 prior lines of systemic therapy
  • For patients refractory/resistant to anti-PD-1/PD-L1 antibodies, there should be no anti-PD-1/PD-L1 treatment-related toxicity from prior therapies
  • Previously untreated for metastatic setting or recurred/metastasized after surgery for locally recurrent or metastatic breast cancer (cohort C), and the time from previous neo-/adjuvant therapy to recurrence met the following requirements: ≥ 6 months interval between the end of neo-/adjuvant paclitaxel-based treatment and the onset of recurrence/metastasis; ≥ 6 months interval between the end of neo-/adjuvant anti-angiogenic treatment and the onset of recurrence/metastasis; ≥ 6 months interval between the end of neo-/adjuvant immunotherapy and recurrence/metastasis
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function
  • Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
  • Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)

Exclusion Criteria:

  • Active leptomeningeal disease or uncontrolled brain metastasis
  • Active autoimmune diseases or history of autoimmune diseases that may relapse
  • Any active malignancy ≤ 2 years
  • Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s)
  • History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc
  • Known history of human immunodeficiency virus (HIV) infection
  • Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers
  • Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
  • Prior allogeneic stem cell transplantation or organ transplantation
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic international normalized ratio (INR) monitoring
  • Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
  • Inability to swallow capsules or disease significantly affecting gastrointestinal function
  • Pregnant or breastfeeding woman NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort A
Subjects will receive 70mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Drug: Sitravatinib
Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Names:
  • MGCD516
Drug: Tislelizumab
Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
  • BGB-A317
Experimental: Cohort B
Subjects will receive 100mg sitravatinib in combination with 200mg tislelizumab until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Drug: Sitravatinib
Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Names:
  • MGCD516
Drug: Tislelizumab
Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
  • BGB-A317
Experimental: Cohort C
Subjects will receive sitravatinib in combination with 200mg tislelizumab and 100 mg/m2 nab-paclitaxel until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
Drug: Sitravatinib
Sitravatinib QD PO Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases
Other Names:
  • MGCD516
Drug: Tislelizumab
Tislelizumab Q3W IV Tislelizumab is a programmed death receptor-1 (PD-1) blocking antibody
Other Names:
  • BGB-A317
Drug: Nab-paclitaxel
Nab-paclitaxel D1, D8 Q3W IV Nab-paclitaxel is a chemotherapy drug which combines the chemotherapy drug paclitaxel with albumin
Other Names:
  • Nanoparticle albumin-bound paclitaxel

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR) by Investigator in Cohort A, Cohort B and Cohort C
Time Frame: Up to 12 months
The number of people with tumor responses according to RECIST (V1.1): the proportion of participants who achieves a best overall response of complete response (CR) or partial response (PR).
Up to 12 months
Number of participants experiencing ≥ Grade 3 TRAEs in Cohort B
Time Frame: Up to 12 months
TRAE are adverse events that occur during or after the first administration of the study drug until 30 days after the study drug is discontinued or the new anticancer treatment is initiated.
Up to 12 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) by Investigator in Cohort A, Cohort B and Cohort C
Time Frame: Up to 12 months
The time from the date that response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first.
Up to 12 months
Disease Control Rate (DCR) by Investigator in Cohort A, Cohort B and Cohort C
Time Frame: Up to 12 months
The proportion of participants who achieves a best overall response of CR, PR or stable disease(SD).
Up to 12 months
Progression-free Survival (PFS) by Investigator in Cohort A, Cohort B and Cohort C
Time Frame: Up to 12 months
Time from the date of randomization to the date of progressive disease (PD) or death, whichever occurs first.
Up to 12 months
One-year overall survival (OS) rate in Cohort A, Cohort B and Cohort C
Time Frame: Up to 12 months
OS defined as the time from the date of randomization to the date of death due to any reason. One-year survival rate (percentage of subjects alive at 1 year) was estimated from OS data.
Up to 12 months
Number of participants experiencing Adverse Events (AEs), Treatment-Related Adverse Events (TRAEs) or Serious Adverse Events (SAEs) in Cohort A, Cohort B and Cohort C
Time Frame: Up to 12 months
Adverse Events (AEs) according to CTCAE v5.0
Up to 12 months
Patient report outcomes (PROs) based on the EORTC QLQ-C30 (V.3) Quality of Life Questionnaire in Cohort B and Cohort C
Time Frame: Through study completion, an average of 1 year
Evaluating the Quality of Life of participants as assessed by EORTC QLQ-C30 Questionnaire
Through study completion, an average of 1 year
Potential biomarkers associated with efficacy, drug resistance, and/or disease progression (PD) in tumor tissues in Cohort A, Cohort B and Cohort C
Time Frame: Through study completion, an average of 1 year
Potential biomarkers in tumor tissues associated with efficacy
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fudan University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: ZhiMin Shao, MD, PhD, Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Lei Fan, Xiyu Liu, Xi Jin, Yunsong Yang, Li Chen, Xin Hu, Zhonghua Wang, Yizhou Jiang, and Zhimin Shao. The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer.Journal of Clinical Oncology 2022 40:16_suppl, 1070-1070
  • L. Liu, X. Jin, Y. Xu, S. Wu, Y. Yang, L. Chen, W. Zhang, L. Ma, X. Hu, Z. Wang, Y. Jiang, Z. Shao. The safety, tolerability, and preliminary antitumor activity of sitravatinib plus tislelizumab in patients (pts) with locally recurrent or metastatic triple negative breast cancer (TNBC): a multi-cohort, phase II trial. Annals of Oncology (2022) 16 (suppl_1): 100102-100102. 10.1016/iotech/iotech100102

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2021

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2021

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 20, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BGB-900-2001-IIT

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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