Back to resultsGuided Treatment Based on Mini-PDX in Metastatic Triple Negative Breast Cancer
Primary Purpose
Triple Negative Breast Cancer
Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Personalized treatment guided by mini-PDX and RNA sequencing
Nab paclitaxel
Eribulin
Vinorelbine
Gemcitabine
Capecitabine
Sponsored by
About this trial
This is an interventional treatment trial for Triple Negative Breast Cancer
Eligibility Criteria
Inclusion Criteria:
- 1) Women aged 18-70 years;
- 2) an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- 3) Estimated lifetime is ≥ 3 months;
- 4) Histopathologically confirmed recurrent (unresectable) or metastatic triple-negative breast cancer; ER and PR negative is defined as ER <1% positive, PR <1% positive. HER-2 negative is defined as HER-2 (-) or (1+) by immunohistochemistry, HER-2 (2+) must be tested by FISH with negative result, HER-2 (1+) (1+), FISH is optional and negative;
- 5) Have at least one measurable target lesion according to RECIST 1.1 criteria;
- 6) Biopsy of the tumor lesion and the specimen passes laboratory quality control;
- 7) A minimum of 2 prior cytotoxic chemotherapy regimens (including at least one line of platinum-containing regimen) in metastatic settings are required prior to enrollment in this trial;
8) Adequate organ function, i.e. meeting the following criteria.
- Hb ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 109 /L; PLT ≥ 75 × 109 /L.
- Liver function: total bilirubin TBIL ≤ 1.5×ULN (upper limit of normal); ALT and AST ≤ 3×ULN.
- serum Cr ≤ 1.5×ULN.
- 9) Subjects voluntarily joined the study, signed the informed consent form, were compliant and cooperated with the follow-up.
Exclusion Criteria:
- 1）Pregnancy or lactation；
- 2）History of autoimmune disease；
- 3）Anticancer- and radiation therapy-related toxicities have not resolved or downgraded to Grade 1 or less;
- 4) Symptomatic central nervous system (CNS) disease;
- 5) Previous treatment of Immune checkpoint inhibitors;
- 6) History of other malignancies within the past five years, with the exception of cured non-malignant melanoma of the skin and carcinoma in situ of the cervix.
Sites / Locations
- Fudan University Shanghai Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Personalized treatment guided by Mini-PDX
Treatment of Physician's Choice (TPC)
Arm Description
The tumor tissue is used for drug sensitivity test by Mini-PDX, and acquiring the genetic information by RNA-sequence. Patients with mTNBC will receive personalized treatment guided by the experimental results of mini-PDX and RNA sequencing.
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
Outcomes
Primary Outcome Measures
Objective response rate
To compare the Objective Response Rate (ORR) of patients who recieve persionalized treatment based on mini-PDX model with ORR of patients who receive Treatment of Physician's Choice (TPC). ORR is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1. ORR will be calculated based on the Investigator assessment of response. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Secondary Outcome Measures
Overall Survival
Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis.
Progression-Free Survival
Progression-free survival is defined as the time from the date of randomization to the first evidence of documented disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Adverse events
Number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04745975
Brief Title
Guided Treatment Based on Mini-PDX in Metastatic Triple Negative Breast Cancer
Official Title
GUided Treatment Based on Mini-PDX in metastaTIc refractOry Triple Negative Breast Cancer(GUMPTION)：a Prospective Randomized Controlled Single Center Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2021 (Actual)
Primary Completion Date
January 2023 (Anticipated)
Study Completion Date
January 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Triple-negative breast cancer constitutes 15-20% of cases of breast cancer and is defined by the absence of estrogen receptors, progesterone receptors, and overexpression or gene amplification of HER2. Although the addition of immune checkpoint inhibitors could improve the outcome of patients with metastatic triple-negative breast cancer (mTNBC), chemotherapy has been the standard of care for systemic treatment for patients with mTNBC. Prognoses remain poor, with reported median overall survival estimates of approximately 18 months or less with available treatments. A meta-analysis of seven clinical trials showed that the median objective response rate (ORR) of second or later line of chemotherapy in mTNBC was only 11%.
Patient-derived xenograft (PDX) tumor model, which preserves the histologic and genetic characteristics of patients' tumors, has shown its predictive value of clinical outcomes and are used for preclinical drug evaluation, biomarker identification, biological studies, and personalized medicine strategies. However, long time period and low success rate has limited its application in clinical practice.
Mini patient derived xenograft (miniPDX) offers an effective alternative as it only takes about 7 days for drug sensitivity test and could thus provide guidance for prompt personalized treatment for each patient.
Thus, the investigators conduct this single-center, prospective, randomized controlled clinical study to investigate the efficacy of guided treatment based on Mini-PDX in patients with metastatic refractory triple negative breast cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Triple Negative Breast Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Personalized treatment guided by Mini-PDX
Arm Type
Experimental
Arm Description
The tumor tissue is used for drug sensitivity test by Mini-PDX, and acquiring the genetic information by RNA-sequence. Patients with mTNBC will receive personalized treatment guided by the experimental results of mini-PDX and RNA sequencing.
Arm Title
Treatment of Physician's Choice (TPC)
Arm Type
Active Comparator
Arm Description
TPC will be administered per standard of care. Patients randomized to TPC will receive chemotherapy, including but not limited to the following agents: nab-paclitaxel, eribulin, vinorelbine, gemcitabine, capecitabine.
Intervention Type
Drug
Intervention Name(s)
Personalized treatment guided by mini-PDX and RNA sequencing
Intervention Description
Personalized treatment guided by mini-PDX and RNA sequencing
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
Nab-paclitaxel 125 mg/m2，ivgtt，d1, 8, 15, q4w
Intervention Type
Drug
Intervention Name(s)
Eribulin
Intervention Description
Eribulin 1.4 mg/m2, d1,8 q3w
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Intervention Description
Vinorelbine 25mg/m2 d1,8, q3w
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Intervention Description
Gemcitabine 1000 mg/m2, d1,8, q3w
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine 1250 mg/m2 bid po
Primary Outcome Measure Information:
Title
Objective response rate
Description
To compare the Objective Response Rate (ORR) of patients who recieve persionalized treatment based on mini-PDX model with ORR of patients who receive Treatment of Physician's Choice (TPC). ORR is defined as the proportion of patients with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST 1.1. ORR will be calculated based on the Investigator assessment of response. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame
Through study completion, an expected average of 1 year
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis.
Time Frame
Through study completion, an expected average of 1 year
Title
Progression-Free Survival
Description
Progression-free survival is defined as the time from the date of randomization to the first evidence of documented disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
Time Frame
Through study completion, an expected average of 1 year
Title
Adverse events
Description
Number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v 5.0
Time Frame
Through study completion, an expected average of 1 year
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
1) Women aged 18-70 years;
2) an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
3) Estimated lifetime is ≥ 3 months;
4) Histopathologically confirmed recurrent (unresectable) or metastatic triple-negative breast cancer; ER and PR negative is defined as ER <1% positive, PR <1% positive. HER-2 negative is defined as HER-2 (-) or (1+) by immunohistochemistry, HER-2 (2+) must be tested by FISH with negative result, HER-2 (1+) (1+), FISH is optional and negative;
5) Have at least one measurable target lesion according to RECIST 1.1 criteria;
6) Biopsy of the tumor lesion and the specimen passes laboratory quality control;
7) A minimum of 2 prior cytotoxic chemotherapy regimens (including at least one line of platinum-containing regimen) in metastatic settings are required prior to enrollment in this trial;
8) Adequate organ function, i.e. meeting the following criteria.
Hb ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 109 /L; PLT ≥ 75 × 109 /L.
Liver function: total bilirubin TBIL ≤ 1.5×ULN (upper limit of normal); ALT and AST ≤ 3×ULN.
serum Cr ≤ 1.5×ULN.
9) Subjects voluntarily joined the study, signed the informed consent form, were compliant and cooperated with the follow-up.
Exclusion Criteria:
1）Pregnancy or lactation；
2）History of autoimmune disease；
3）Anticancer- and radiation therapy-related toxicities have not resolved or downgraded to Grade 1 or less;
4) Symptomatic central nervous system (CNS) disease;
5) Previous treatment of Immune checkpoint inhibitors;
6) History of other malignancies within the past five years, with the exception of cured non-malignant melanoma of the skin and carcinoma in situ of the cervix.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xichun Hu, M.D.
Phone
021-54561523
Email
xchu2009@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Jian Zhang, M.D.
Phone
021-54561523
Email
syner2000@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Xichun Hu, M.D.
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jian Zhang, M.D.
Phone
021-54561523
Email
syner2000@163.com
12. IPD Sharing Statement
Plan to Share IPD
No
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Guided Treatment Based on Mini-PDX in Metastatic Triple Negative Breast Cancer
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