Type I Interferon Alfa-2a in Postmastectomy Breast Reconstruction

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: IFNα-2a

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Shicheng Su

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental: Participants with breast cancer enrolled in grou	Drug: IFNα-2a; After mastectomy, it is used in the cavity of breast before conducting implantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity (DLT)	Dose-limiting toxicity (DLT), defined as certain grade II toxicity such as nephrotoxicity and cardiotoxicity, grade III non-hematologic toxicity and grade IV hematologic toxicity.	7 days after surgery
Maximal tolerable dose (MTD)	Maximal tolerable dose (MTD), defined as a dose level where 2 or more subjects among 6 subjects suffering DLT. If the experiment reached the set maximum dose without any DLT occurring, the maximum dose was defined as MTD.	7 days after surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events (AE)	7 days after surgery
Server adverse events (SAE)	7 days after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Investigators: Principal Investigator: Shicheng Su, M.D.,Ph.D., Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2020
• Primary Completion (Actual): July 14, 2021
• Study Completion (Actual): July 14, 2021

Study Registration Dates

• First Submitted: August 18, 2020
• First Submitted That Met QC Criteria: August 18, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Actual): February 9, 2022
• Last Update Submitted That Met QC Criteria: February 8, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Breast reconstruction; Implants; Interferon (IFN)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferon alpha-2
• Other Study ID Numbers: 2020-KY-051

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No