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An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC. (FUTURE-SUPER)

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ClinicalTrials.gov Identifier: NCT04395989
Recruitment Status : Recruiting
First Posted : May 20, 2020
Last Update Posted : May 20, 2020
Sponsor:
Information provided by (Responsible Party):
Fudan University

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.

Condition or disease Intervention/treatment Phase
TNBC - Triple-Negative Breast Cancer Drug: A1: Pyrotinib with Capecitabine Drug: A2: nab-paclitaxel Drug: B1: everolimus with nab-paclitaxel Drug: B2: nab-paclitaxel Drug: C1: PD-1 with nab-paclitaxel and famitinib Drug: C2: nab-paclitaxel Drug: D1: VEGFR and nab-paclitaxel Drug: D2: nab-paclitaxel Drug: E1: Everolimus with nab-paclitaxel Drug: E2: nab-paclitaxel Phase 2

Detailed Description:
This is a Phase II, open-label, randomized controlled umbrella trial evaluating the efficacy and safety of multiple targeted treatment vs. traditional chemotherapy in patients with unresectable locally advanced or metastatic triple negative breast cancer. The specific grouping of patients' depends on FUSCC 500+ gene panel testing and IHC subtype staining.These tests would be done on their rebiopsy tumor specimen. Specifically, as to TNBC molecular subtyping,FUSCC data identified the genomic aberrations that drive each TNBC subtype by applying an integrative analysis combining somatic mutation, copy number aberrations (CNAs) and gene expression profiles, which classified TNBC patients into four subtypes, namely luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune suppressed (BLIS), and mesenchymal-like (MES). Then, FUSCC conducted a IHC subtyping model to replace complex genomic sequencing, which have been validated in FUSCC cohort.FUSCC 500+ gene panel was developed combining public database(TCGA, METABRIC, 560WES, MSKCC-IMPACT ect.) and FUSCC private TNBC database.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Umbrella Trial Based on Molecular Pathway for Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer (FUTURE SUPER)
Estimated Study Start Date : May 15, 2020
Estimated Primary Completion Date : November 15, 2022
Estimated Study Completion Date : November 15, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: LAR-HER2+
If patients were LAR subtype with HER2 gene activated mutation
Drug: A1: Pyrotinib with Capecitabine
A1: pyrotinib(EGFR-TKI) 400mg qd and capecitabine 1000mg/m2 bid (d1-d14)
Other Name: SHR1258

Drug: A2: nab-paclitaxel
A2: nab-paclitaxel 100mg qw (three week on one week off)

Experimental: LAR-PAM+
If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation
Drug: B1: everolimus with nab-paclitaxel
B1: everolimus 10mg qd combined with nab-paclitaxel 100mg qw (three week on one week off)

Drug: B2: nab-paclitaxel
B2: nab-paclitaxel 100mg qw (three week on one week off)

Experimental: IM
If patients were IM subtype (CD8 positive T cell more than 20%)
Drug: C1: PD-1 with nab-paclitaxel and famitinib
C1: PD-1 antibody SHR1210 200mg q2w and nab-paclitaxel 100mg qw (three week on one week off) and famitinib 20mg qd
Other Names:
  • Camrelizumab
  • SHR1210

Drug: C2: nab-paclitaxel
C2: nab-paclitaxel 100mg qw (three week on one week off)

Experimental: BLIS
If patients were BLIS subtype or MES subtype and without PI3K/AKT/mTOR pathway activation
Drug: D1: VEGFR and nab-paclitaxel
D1: VEGFR BP102 10mg/kg q2w and nab-paclitaxel 100mg qw (three week on one week off).
Other Name: BP102

Drug: D2: nab-paclitaxel
D2: nab-paclitaxel 100mg qw (three week on one week off)

Experimental: MES-PAM+
If patients were MES subtype and had PI3K/AKT/mTOR pathway activation
Drug: E1: Everolimus with nab-paclitaxel
E1: Everolimus 10mg qd with nab-paclitaxel 100mg qw (three week on one week off)

Drug: E2: nab-paclitaxel
E2: nab-paclitaxel 100mg qw (three week on one week off)




Primary Outcome Measures :
  1. PFS of Each Arm [ Time Frame: approximately 3 years ]
    Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study time to progressive disease (according to RECIST1.1) of each arm

  2. PFS of Precision Treatment [ Time Frame: approximately 3 years ]
    Randomization until the first occurrence of disease progression or death from any cause, which ever occurs first, through the end of study (approximately 3 years) ] time to progressive disease of precision treatment


Secondary Outcome Measures :
  1. OS of Each Arm [ Time Frame: approximately 3 years ]
    Randomization to death from any cause, through the end of study of Each Arm

  2. OS of Precision Treatment [ Time Frame: approximately 3 years ]
    Randomization to death from any cause, through the end of study of Precision Treatment

  3. Objective Response Rate [ Time Frame: approximately 3 years ]
    Percentage of Participants With an Objective Response of Complete Response (CR) or Partial Response (PR) According to RECIST v1.1 in all Participants



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04395989


Contacts
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Contact: Zhimin Shao, M.D. 86-021-64175590 ext 88807 zhimingshao@yahoo.com
Contact: Lei Fan, M.D. 86-021-64175590 ext 66088 drfanlei@gmail.com

Locations
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China, Shanghai
Cancer Hospital Affiliated to Fudan University Recruiting
Shanghai, Shanghai, China, 200032
Contact: Zhimin Shao, MD, PhD    +86-021-64175590 ext 88807    zhimingshao@yahoo.com   
Sponsors and Collaborators
Fudan University
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Responsible Party: Fudan University
ClinicalTrials.gov Identifier: NCT04395989    
Other Study ID Numbers: SCHBCC-N031
First Posted: May 20, 2020    Key Record Dates
Last Update Posted: May 20, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Fudan University:
TNBC
Molecular Subtype
Precision Treatment
Umbrella Trial
First Line
Additional relevant MeSH terms:
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Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Capecitabine
Everolimus
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs