Clinical trial NCT04522557: Type I Interferon Alfa-2a in Postmastectomy Breast Reconstruction
Official title: Type I Interferon Alfa-2a in Postmastectomy Breast Reconstruction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Neoplasms
Keywords: Breast reconstruction
Implants
Interferon (IFN)
Lead sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 21
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Implant-based reconstruction have become the most popular choices of reconstruction for women undergoing breast mastectomy. Postoperative complications like infection and tumor recurrence limit its application. Interferons (IFNs) are pleiotropic cytokines that involve in immunoregulatory, anticancer and restricting infection. Especially, type I IFN signaling is reported favourable for the success of conventional chemotherapeutics, radiotherapy and immunotherapy. In addition, type I IFN can regulate the activity of almost all immune cell types (including T cells, macrophages and innate lymphocytes), creating a well-established immune environment to defense infectious and relapsing disease. Implants are rapidly coated with extracellular matrix proteins and immune protein components for the formation of a typical capsule. At the specific time point before implantation, the locally utilized of IFN in intracavity breast is assumed to modify cellular immune responses thus contributing to decreasing infection and tumor recurrence.

PURPOSE: This non-randomized phase I trial aims to explore dose range of IFNα-2a. Adverse events are observed to assess drug safety and human tolerance index.


Eligibility criteria: Inclusion Criteria:

1. Signed the informed consent.
2. Female aged between 18 and 70 years.
3. Pathologically diagnosed operable breast cancer.
4. WHO Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
5. Newly diagnosed breast cancer.
6. The important organ functions meet the following criteria:

   * WBC \>=3.0 x 10\^9/L; Neutrophilic granulocytes \>=1.5×10\^9/L; Platelet \>=100 x 10\^9/L; Hb \>=9 g/dL;
   * Total bilirubin no more than 1.5 times the normal upper limit (ULN); AST and ALT no more than 1.5 times ULN; AKP no more than 2.5 times ULN;
   * Serum creatinine no more than 1.5 times ULN or Clearance rate of creatinine \>= 60ml/min;
   * Thyroid stimulating hormone (TSH) \<= ULN (T3, T4 levels need to be detected simultaneously if abnormalities, the patient can be included if T3, T4 levels is normal);
   * LVEF basement \>= 50%.

Exclusion Criteria:

1. Evidence of distant metastasis.
2. Any contraindication of nipple-areolar complex (NAC) saving mastectomy (NSM):

   * Intraoperative biopsy revealed carcinoma invasion of NAC.
   * Paget's disease of breast.
   * Tumor distant from NAC less than 1 cm.
3. Any invasive malignancy diagnosed within previous 5 years (other than successfully treated cervical carcinoma in situ, skin basal cell carcinoma or cutaneous squamous cell carcinoma).
4. At least 4 months since prior interferon therapy.
5. At least 3 weeks since prior major surgery requiring general anesthesia.
6. At least 3 weeks since prior radiotherapy or chemotherapy.
7. Hypersensitivity to interferon or other components: urticaria, angioedema, bronchial stenosis, anaphylaxis, or Stevens-Johnson syndrome.
8. Prior organ allograft.
9. Use of an unlicensed or other investigational drug within 4 weeks.
10. Any severe comorbidities, inability to give informed consent or unavailability for follow-up, including but not limited to any of the following:

    * Heart failure above NYHA class 2 level; high-risk uncontrollable arrhythmia; unstable angina pectoris; myocardial infarction within 1 intervention.
    * Chronic obstructive pulmonary disease requires treatment.
    * Chronic liver disease (cirrhosis, chronic active hepatitis, etc.).
    * Cerebrovascular accident occurred within 6 months.
    * Severe epilepsy or central nervous system diseases.
    * Hypertension which cannot be well controlled by antihypertensive drugs.
    * Abnormal coagulation, bleeding tendency, or receiving thrombolysis or anticoagulant therapy.
    * Chronic renal insufficiency.
    * Active infection.
    * Psychiatric disability, etc.
11. Pregnant or lactating women.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: 7 days after surgery
measure: Maximal tolerable dose (MTD)
timeFrame: 7 days after surgery
Secondary outcomes:
measure: Adverse events (AE)
timeFrame: 7 days after surgery
measure: Server adverse events (SAE)
timeFrame: 7 days after surgery
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Shicheng Su
state: Guangdong
Study officials:
affiliation: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
name: Shicheng Su, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: