Guided Treatment Based on Mini-PDX in Metastatic Triple Negative Breast Cancer

NCT ID: NCT04745975

Last Updated: 2022-04-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-01
• Study Completion Date: 2023-01-31

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.

Conditions

Triple Negative Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Personalized treatment guided by Mini-PDX

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.

Group Type: EXPERIMENTAL

Personalized treatment guided by mini-PDX and RNA sequencing

Intervention Type: DRUG

Personalized treatment guided by mini-PDX and RNA sequencing

Treatment of Physician's Choice (TPC)

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.

Group Type: ACTIVE_COMPARATOR

Nab paclitaxel

Intervention Type: DRUG

Nab-paclitaxel 125 mg/m2，ivgtt，d1, 8, 15, q4w

Eribulin

Intervention Type: DRUG

Eribulin 1.4 mg/m2, d1,8 q3w

Vinorelbine

Intervention Type: DRUG

Vinorelbine 25mg/m2 d1,8, q3w

Gemcitabine

Intervention Type: DRUG

Gemcitabine 1000 mg/m2, d1,8, q3w

Capecitabine

Intervention Type: DRUG

Capecitabine 1250 mg/m2 bid po

Interventions

Personalized treatment guided by mini-PDX and RNA sequencing

Personalized treatment guided by mini-PDX and RNA sequencing

Intervention Type: DRUG

Nab paclitaxel

Nab-paclitaxel 125 mg/m2，ivgtt，d1, 8, 15, q4w

Intervention Type: DRUG

Eribulin

Eribulin 1.4 mg/m2, d1,8 q3w

Intervention Type: DRUG

Vinorelbine

Vinorelbine 25mg/m2 d1,8, q3w

Intervention Type: DRUG

Gemcitabine

Gemcitabine 1000 mg/m2, d1,8, q3w

Intervention Type: DRUG

Capecitabine

Capecitabine 1250 mg/m2 bid po

Intervention Type: DRUG

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.

1. Hb ≥ 90 g/L (no transfusion within 14 days); ANC ≥ 1.5 × 109 /L; PLT ≥ 75 × 109 /L.

2. Liver function: total bilirubin TBIL ≤ 1.5×ULN (upper limit of normal); ALT and AST ≤ 3×ULN.

3. 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fudan University

OTHER

Sponsor Role: lead

Responsible Party

Xichun Hu

Director of Medical Oncology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Xichun Hu, M.D.

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xichun Hu, M.D.

Role: CONTACT

xchu2009@hotmail.com

021-54561523

Jian Zhang, M.D.

Role: CONTACT

syner2000@163.com

021-54561523

Facility Contacts

Jian Zhang, M.D.

Role: primary

syner2000@163.com

021-54561523

Other Identifiers

GUMPTION

Identifier Type: -

Identifier Source: org_study_id