Apatinib in Neoadjuvant Therapy for Patients With Breast Cancer

• ClinicalTrials.gov Identifier: NCT03580395
• Recruitment Status: Enrolling by invitation
• First Posted: July 9, 2018
• Last Update Posted: July 9, 2021
• Sponsor: Hebei Medical University Fourth Hospital
• Information provided by (Responsible Party): Liu Yunjiang, Hebei Medical University Fourth Hospital

Study Description

Brief Summary:

To verify the role of apatinib in neoadjuvant therapy for breast cancer, the investigators designed a prospective, randomized, parallel-controlled phase II/III trial, to investigate the efficacy and safety of apatinib combined with TP (paclitaxel + cisplatin) or TP regimen alone as neoadjuvant therapy for stage II-III breast cancer treatment. 100 cases of eligible patients were diagnosed by core needle biopsy and immunohistochemistry, with the molecular subtypes of triple-negative, HER2+ or Luminal B, evaluated by pathological complete remission (pCR), objective response rate (ORR), adverse events, disease free survival (DFS) and OS, aiming at providing a new way for neoadjuvant therapy in breast cancer and anti-angiogenic treatment of malignant tumors.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Apatinib; Drug: paclitaxel; Drug: cisplatin	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Apatinib Added to Docetaxel and Cisplatin Neoadjuvant Therapy for Patients With Breast Cancer: a Randomized, Parallel Controlled Phase II Trial
• Actual Study Start Date: June 1, 2017
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: apatinib+TP; TP neoadjuvant chemotherapy (paclitaxel 165mg/m2 day 1, cisplatin 40mg, day 1-3) combined with apatinib (received TP concurrently with apatinib 500mg, day1-21).	Drug: Apatinib; 500mg, day1-21,neoadjuvant therapy; Drug: paclitaxel; paclitaxel 165mg/m2 day 1; Drug: cisplatin; cisplatin 40mg, day 1-3
Sham Comparator: TP; TP neoadjuvant chemotherapy alone (paclitaxel 165mg/m2 day 1, cisplatin 40mg, day 1-3).	Drug: paclitaxel; paclitaxel 165mg/m2 day 1; Drug: cisplatin; cisplatin 40mg, day 1-3

Outcome Measures

Primary Outcome Measures :

1. The primary endpoint is pathological complete remission (pCR) [ Time Frame: 4 months ]
   pCR was defined as no histological evidence of invasive tumor cells in the surgical breast specimen and draining nodes. The presence of residual ductal carcinoma-in situ was not included in the pCR category after neoadjuvant treatment.

Secondary Outcome Measures :

1. The second endpoint includes the objective response rate (ORR) [ Time Frame: 4 months ]
   Evaluation of tumor response was performed by independent evaluators who were blinded to the arm assignment consisted of 2 oncologists and 2 pathologists. Tumor response status was defined according to the Response Evaluation Criteria in Solid Tumors Committee (RECIST). Specifically, the complete response (CR) was defined as the disappearance of all the lesions both in breast specimen and draining nodes; The primary endpoint ORR composed of tumor response classifications of CR and partial response (PR).
2. Adverse events (AE) [ Time Frame: 4 months ]
   Adverse events (AE) were monitored on an ongoing basis and classified according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0. Patients were assessed for toxicities before each administration., and toxicity was graded accordingly.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. breast invasive carcinoma diagnosed by core needle biopsy, without previous treatments for breast cancer;
2. with the molecular subtypes of triple-negative, HER2+ or Luminal B, confirmed by immunohistochemistry;
3. breast cancer within stage IIb-IIIc, planned to receive neoadjuvant therapy;
4. women aged from 18 to 70 years old;
5. required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1;
6. left ventricular ejection fraction (LVEF) greater than 55% without clinical symptoms or signs of heart failure;
7. Adequate bone marrow, with white blood cell ≥4.0×109 /L，neutrophils ≥2.0×109 /L, platelet ≥100×109 /L, hemoglobin ≥ 90 g/L；
8. Serum creatinine ranges from 44 to 133 mol/L;
9. Glutamic pyruvic transaminase and Glutamic-oxalacetic Transaminase ≤2 times to superior limit of normal value;
10. bilirubin ≤ superior limit of normal value;
11. Expected survival ≥ 12 months;
12. pregnancy tests must be negative, and the couples of patients should agree to use effective contraception during treatment and the following one year;
13. approved by the institutional ethnics committee of the Fourth Hospital of Hebei Medical University, with signature to the Informed consent.

Exclusion Criteria:

1. severe systemic infection;
2. being allergic or intolerant to apatinib, paclitaxel, cisplatin;
3. having received any testing drugs, radiotherapy or other chemotherapy drugs within 30 days before being enrolled in this trial;
4. uncontrolled hypertension, severe heart function;
5. researchers believe that participating in the test does not meet the best interests of the patients (e.g. cause adverse health) or may interfere with the evaluation of response.

Contacts and Locations

Locations

China, Hebei

Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province

Shijiazhuang, Hebei, China, 050011

Sponsors and Collaborators

Hebei Medical University Fourth Hospital

Investigators

• Principal Investigator: Yunjiang Liu, MD.,PhD; Fourth Hospital of Hebei Medical University, Tumor Hospital of Hebei Province

More Information

• Responsible Party: Liu Yunjiang, Professor, Director and Vice-president, Hebei Medical University Fourth Hospital
• ClinicalTrials.gov Identifier: NCT03580395
• Other Study ID Numbers: HebeiMUFH
• First Posted: July 9, 2018
• Last Update Posted: July 9, 2021
• Last Verified: July 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

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

Keywords provided by Liu Yunjiang, Hebei Medical University Fourth Hospital:

apatinib; neoadjuvant therapy; breast cancer

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Paclitaxel; Apatinib; Antineoplastic Agents, Phytogenic; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Protein Kinase Inhibitors; Enzyme Inhibitors