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

• ClinicalTrials.gov Identifier: NCT04395989
• Recruitment Status: Active, not recruiting
• First Posted: May 20, 2020
• Last Update Posted: December 22, 2023
• Sponsor: Fudan University
• Information provided by (Responsible Party): Zhimin Shao, Fudan University

Tracking Information

• First Submitted Date: May 15, 2020
• First Posted Date: May 20, 2020
• Last Update Posted Date: December 22, 2023
• Actual Study Start Date: July 28, 2020
• Actual Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 15, 2023)

Progression Free Survival (PFS) [ Time Frame: approximately 3 years ]

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

Original Primary Outcome Measures (submitted: May 19, 2020)

• 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
• 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

Current Secondary Outcome Measures (submitted: December 17, 2023)

• Overall Survival (OS) [ Time Frame: approximately 3 years ]
  Refers to the period from the date of the first study dose to the date of death for any reason.
• Objective response rate (ORR) [ Time Frame: approximately 3 years ]
  Defined as the proportion of patients whose tumors shrink to a certain amount and remain for a certain period of time, including cases of CR and PR.
• Duration of Response (DoR) [ Time Frame: approximately 3 years ]
  Defined as the date from the first recording of tumor response (assessed according to RECIST 1.1) to the first recording of the objective progression of the tumor (assessed according to RECIST 1.1) or to the date of death for any reason, whichever occurs first.
• Disease Control Rate (DCR) [ Time Frame: approximately 3 years ]
  The proportion of subjects who received treatment and whose best overall response (BOR) was assessed as complete response (CR), partial response (PR) and stable disease (SD) ≥4 weeks according to RECIST1.1.
• Safety: Adverse Events (AE) [ Time Frame: approximately 3 years ]
  AE refers to any untoward medical occurrence in a study subject administered an investigational product which does not necessarily have a causal relationship with the treatment. AE is assessed according to the NCI-CTC AE 5.0.

Original Secondary Outcome Measures (submitted: May 19, 2020)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Umbrella Trial Based on Molecular Pathway for Patients With Metastatic TNBC.
• Official Title: An Umbrella Trial Based on Molecular Pathway for Patients With Unresectable Locally Advanced or Metastatic Triple Negative Breast Cancer (FUTURE SUPER)
• 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: TNBC - Triple-Negative Breast Cancer

Intervention

• Drug: A1: Pyrotinib with nab-paclitaxel
  A1: pyrotinib(EGFR-TKI) 400mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
  Other Name: SHR1258
• Drug: A2: nab-paclitaxel
  A2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• Drug: B1: everolimus with nab-paclitaxel
  B1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• Drug: B2: nab-paclitaxel
  B2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• Drug: C1: PD-1 with nab-paclitaxel and famitinib
  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
  Other Names:

  • Camrelizumab
  • SHR1210
• Drug: C2: nab-paclitaxel
  C2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• Drug: D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine
  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.
  Other Name: Bevacizumab (BP102)
• Drug: D2: nab-paclitaxel, with maintenance of capecitabine
  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.
• Drug: E1: everolimus with nab-paclitaxel
  E1: everolimus 10mg po qd + nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle
• Drug: E2: nab-paclitaxel
  E2: nab-paclitaxel 100mg/m2 d1,8,15 ivgtt, 4 weeks as a cycle

Study Arms

• Experimental: LAR-HER2mut
  If patients were LAR subtype with HER2 gene activated mutation
  Interventions:

  • Drug: A1: Pyrotinib with nab-paclitaxel
  • Drug: A2: nab-paclitaxel
• Experimental: LAR-PI3K/AKTmut
  If patients were LAR subtype without HER2 gene activated mutation, but had PI3K/AKT/mTOR pathway mutation
  Interventions:

  • Drug: B1: everolimus with nab-paclitaxel
  • Drug: B2: nab-paclitaxel
• Experimental: IM
  If patients were IM subtype (CD8 positive T cell more than 10%)
  Interventions:

  • Drug: C1: PD-1 with nab-paclitaxel and famitinib
  • Drug: C2: nab-paclitaxel
• Experimental: BLIS/MES-PI3K/AKTWT
  If patients were BLIS subtype or MES subtype without PI3K/AKT/mTOR pathway activation
  Interventions:

  • Drug: D1: VEGFR and nab-paclitaxel, with maintenance of VEGFR and capecitabine
  • Drug: D2: nab-paclitaxel, with maintenance of capecitabine
• Experimental: MES-PI3K/AKTmut
  If patients were MES subtype and had PI3K/AKT/mTOR pathway activation
  Interventions:

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 14, 2023): 139
• Original Estimated Enrollment (submitted: May 19, 2020): 138
• Estimated Study Completion Date: December 31, 2024
• Actual Primary Completion Date: May 31, 2023 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT04395989
• Other Study ID Numbers: SCHBCC-N031
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Zhimin Shao, Fudan University
• Original Responsible Party: Fudan University
• Current Study Sponsor: Fudan University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Fudan University
• Verification Date: December 2023