NCT04395989

Brief Summary

This is a Phase II, open-label, randomized controlled umbrella trial evaluating the efficacy and safety of multiple targeted treatment in patients with metastaticTNBC.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
139

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2020

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 15, 2020

Completed
5 days until next milestone

First Posted

Study publicly available on registry

May 20, 2020

Completed
2 months until next milestone

Study Start

First participant enrolled

July 28, 2020

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2023

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2024

Completed
Last Updated

December 22, 2023

Status Verified

December 1, 2023

Enrollment Period

2.8 years

First QC Date

May 15, 2020

Last Update Submit

December 17, 2023

Conditions

Keywords

TNBCMolecular SubtypePrecision TreatmentUmbrella TrialFirst Line

Outcome Measures

Primary Outcomes (1)

  • Progression Free Survival (PFS)

    Refers to the time between the patient's enrollment and any recorded tumor progression or death from any cause.

    approximately 3 years

Secondary Outcomes (5)

  • Overall Survival (OS)

    approximately 3 years

  • Objective response rate (ORR)

    approximately 3 years

  • Duration of Response (DoR)

    approximately 3 years

  • Disease Control Rate (DCR)

    approximately 3 years

  • Safety: Adverse Events (AE)

    approximately 3 years

Study Arms (5)

LAR-HER2mut

EXPERIMENTAL

If patients were LAR subtype with HER2 gene activated mutation

Drug: A1: Pyrotinib with nab-paclitaxelDrug: A2: nab-paclitaxel

LAR-PI3K/AKTmut

EXPERIMENTAL

If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation

Drug: B1: everolimus with nab-paclitaxelDrug: B2: nab-paclitaxel

IM

EXPERIMENTAL

If patients were IM subtype (CD8 positive T cell more than 10%)

Drug: C1: PD-1 with nab-paclitaxel and famitinibDrug: C2: nab-paclitaxel

BLIS/MES-PI3K/AKTWT

EXPERIMENTAL

If patients were BLIS subtype or MES subtype without PI3K/AKT/mTOR pathway activation

Drug: D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabineDrug: D2: nab-paclitaxel, with maintenance of capecitabine

MES-PI3K/AKTmut

EXPERIMENTAL

If patients were MES subtype and had PI3K/AKT/mTOR pathway activation

Drug: E1: everolimus with nab-paclitaxelDrug: E2: nab-paclitaxel

Interventions

A1: pyrotinib(EGFR-TKI) 400mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

Also known as: SHR1258
LAR-HER2mut

A2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

LAR-HER2mut

B1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

LAR-PI3K/AKTmut

B2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

LAR-PI3K/AKTmut

C1: PD-1 antibody SHR1210 200mg d1,15 ivgtt + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt + famitinib 20mg po qd, 4 weeks as a cycle

Also known as: Camrelizumab, SHR1210
IM

C2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

IM

D1: VEGFR bevacizumab 10mg/kg d1,15 ivgtt + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle. Capecitabine with bevacizumab maintenance if intolerable toxicity was observed with no progression. Capecitabine maintenance 1000mg/m2 po bid d1-d14 every 3 weeks and bevacizumab 10mg/kg d1,15 ivgtt every 4 weeks.

Also known as: Bevacizumab (BP102)
BLIS/MES-PI3K/AKTWT

D2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle. Capecitabine maintenance if intolerable toxicity was observed with no progression. Capecitabine maintenance 1000mg/m2 po bid d1-d14 every 3 weeks.

BLIS/MES-PI3K/AKTWT

E1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

MES-PI3K/AKTmut

E2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

MES-PI3K/AKTmut

Eligibility Criteria

Age18 Years - 70 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ECOG Performance Status of 0-1
  • Expected lifetime of not less than three months
  • Metastatic or locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
  • Cancer stage: recurrent or metastatic breast cancer; Local recurrence be confirmed by the researchers could not be radical resection.
  • Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)
  • Patients had received no previous chemotherapy or targeted therapy for metastatic triple-negative breast cancer
  • For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm
  • Have the cognitive ability to understand the protocol and be willing to participate and to be followed up.

You may not qualify if:

  • Symptomatic, untreated, or actively progressing CNS metastases
  • Active or history of autoimmune disease or immune deficiency
  • Active hepatitis B or hepatitis C
  • Significant cardiovascular disease
  • History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
  • Treatment with taxel-based chemotherapy within 6 months
  • Treatment with chemotherapy, radiotherapy,immunotherapy or surgery (outpatient clinic surgery excluded)within3 weeks prior to initiation of study treatment.
  • Pregnancy or breastfeeding, or intention of becoming pregnant during the study
  • Previous received anti-VEGFR small molecule tyrosine kinase inhibitors (e.g. famitinib, sorafenib, Sunitinib, regorafenib, etc.) for treatment of the patients .
  • A history of bleeding, any serious bleeding events.
  • Important blood vessels around tumors has been infringed and high risk of bleeding.
  • Long-term unhealing wound or incomplete healing of fracture
  • Urine protein ≥2+ and 24h urine protein quantitative \> 1 g.
  • Arrhythmia for long-term use of anti-arrhythmic drugs and New York heart association class II or higher cardiac insufficiency

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Cancer Hospital Affiliated to Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (1)

  • Fan L, Wang ZH, Ma LX, Wu SY, Wu J, Yu KD, Sui XY, Xu Y, Liu XY, Chen L, Zhang WJ, Jin X, Xiao Q, Shui RH, Xiao Y, Wang H, Yang YS, Huang XY, Cao AY, Li JJ, Di GH, Liu GY, Yang WT, Hu X, Xia Y, Liang QN, Jiang YZ, Shao ZM. Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial. Lancet Oncol. 2024 Feb;25(2):184-197. doi: 10.1016/S1470-2045(23)00579-X. Epub 2024 Jan 8.

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

130-nm albumin-bound paclitaxelfamitinibcamrelizumabCapecitabineBevacizumab

Condition Hierarchy (Ancestors)

Breast NeoplasmsNeoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

DeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsFluorouracilUracilPyrimidinonesDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of General Surgery of Fudan Shanghai Cancer Center

Study Record Dates

First Submitted

May 15, 2020

First Posted

May 20, 2020

Study Start

July 28, 2020

Primary Completion

May 31, 2023

Study Completion

December 31, 2024

Last Updated

December 22, 2023

Record last verified: 2023-12

Locations