Secondary lymphedema associated with the treatment of breast cancer MedDRA version: 20.0 Level: LLT Classification code 10036389 Term: Postmastectomy lymphedema syndrome System Organ Class: 100000004863 MedDRA version: 20.0 Level: LLT Classification code 10025233 Term: Lymphedema System Organ Class: 100000004866 MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Lymfactin
Product Code: LX-1101
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Not known
Current Sponsor code: LX-1101
Other descriptive name: AdAptVEGF-C adenoviral ve
Sponsors
Herantis Pharma Plc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female or male patients with secondary lymphedema associated with the treatment of breast cancer and a. Has undergone sentinel lymph node biopsies and/or lymph node resection in the axilla on the affected side of their breast cancer with initial N1-N2a staging and lymph node metastasis in = 9 axillary lymph nodes. b. Requires garment use as a compression treatment for the lymphedema in the affected arm. c. Has the volume of the affected arm at least 10% greater than the unaffected arm following 7 days without compression garment. d. Has the presence of pitting edema in the affected arm without compression garment. e. Has had lymphedema for less than 5 years. 2. No evidence of recurrent or active breast cancer for at least 2 years after the breast cancer surgery and/or the end of chemotherapy and/or radiotherapy (excluding endocrine treatment). 3. The patient understands and voluntarily signs the written informed consent prior to any screening procedure. 4. 18-70 years of age at time of the informed consent. 5. ECOG Performance Status of 0 or 1. 6. BMI between 18 and 32 inclusive. 7. PET CT scan of the chest and the abdomen within 45 days before the study treatment without signs of active breast cancer or any other malignancy. 8. Adequate hematologic and end-organ function: a. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 x the institutional upper limit of normal (ULN) b. Bilirubin = 1.5 x ULN (except in patients with previously documented Gilbert’s syndrome, in which case total bilirubin = 3 x ULN) c. INR and aPTT = 1.5 x ULN (for patients requiring therapeutic anticoagulation therapy, a stable INR = 2,5) d. Serum creatinine = 1,5 x ULN or creatinine clearance = 50 ml/min e. Absolute neutrophil count (ANC) = 1,5 E9/l f. Platelet count = 100 E9/l g. Hemoglobin = 100 g/l 9. Willingness to comply with scheduled visits, laboratory assessments, and other study-related procedures due to the regulatory requirements related to gene based therapies. 10. Non-smoker or willing to stop smoking or use of nicotine-containing products for at least 4 weeks prior to the study entry. 11. Negative urine pregnancy test (only patients with childbearing potential) at screening and use of adequate contraceptive measures from screening until six months after the study treatment administration: a) A patient with childbearing potential should be using a reliable contraception method: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal, progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. b) A male patient is not allowed to donate sperm.?? c) A patient with no current heterosexual relationship may be included according to the judgement of the Investigator. d) For a patient in postmenopausal state neither contraception nor a pregnancy test is required. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal
Exclusion criteria
Exclusion criteria: 1. Diagnosed for T4 and/or N2b/N3 stage breast cancer at the time of the original diagnosis. 2. Evidence (clinical, laboratory or imaging) or history of a neoplasm other than breast cancer (except basal cell carcinoma or cervical in situ carcinoma). 3. Diagnosed for metastatic breast cancer. 4. Pregnancy, lactation or a positive or indeterminate pregnancy test. 5. Current treatment with COX-2 inhibitors should be interrupted from 2 weeks prior until 4 weeks posttreatment. 6. Previous treatment with, or participation in a trial of a gene therapy product. 7. Participation in a clinical trial, which has included interventions in the preceding 6 months or will involve future interventions. Participation in a noninterventional clinical trial, or in a non-interventional follow-up of any clinical trial, does not make the patient inappropriate for the entry into this study. 8. Current treatment with systemic immunosuppressive drugs. 9. Current history of drug abuse, including nicotinecontaining products, or alcohol abuse. 10. Known human immunodeficiency virus- or acquired immunodeficiency syndrome-related illness. 11. History of hepatic dysfunction, cirrhosis, or hepatitis. 12. Allergy to any ingredients of the Lymfactin® solution for injection (glycerol, N-2-hydroxyethylpiperazine- N´-2-ethanesulfonic acid (HEPES), sodium hydroxide). 13. Other concurrent severe acute and/or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with the study participation or study drug administration, that would, in the Investigator’s judgement, affect the patient's ability to follow study-related procedures, or that may interfere with the interpretation of study results and would make the patient inappropriate for the entry into this study. 14. Doubtful availability, in the opinion of the Investigator, to complete the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of Lymfactin® in patients with secondary lymphedema associated with the treatment of breast cancer by comparing the effects of active study treatment Lymfactin® to placebo. Efficacy of Lymfactin® will be evaluated by the change in the volume of the affected arm, quantitative lymphoscintigraphy and patient quality of life assessment.;Secondary Objective: To assess the safety and tolerability of Lymfactin® by comparing the effects of active study treatment to placebo, to investigate the biodistribution of Lymfactin® in blood and in wound secretion, the development of anti-Lymfactin® antibodies, the VEGF-C concentration in wound secretion and the systemic VEGF-C concentration after Lymfactin® administration. Exploratory Study Objectives: To evaluate two new methods in the assessment of lymphedema: MRI lymphangiography, and PWC measurement for water content and edema in tissue (MoistureMeterD Compact, Delfin Technologies).;Primary end point(s): Efficacy is the primary endpoint of this study. The effects of the treatment on the signs and symptoms of lymphedema will be assessed by comparing the effects of the active study treatment Lymfactin® to placebo up to 36 months post-treatment by: • The measurement of the volume of the affected arm and the unaffected arm. • Quantitative lymphoscintigraphy (99Tc-nanocolloid clearance rate) with calculation of transport index (change from baseline) • Patient quality of life assessment using the Lymphedema Quality of Life Inventory (LQOLI) filled out by the patients (change from baseline).;Timepoint(s) of evaluation of this end point: as spesified | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety endpoints To assess the safety of Lymfactin® treatment by: • Incidence, type and severity of clinically significant adverse events (based on NCI CTCAE v4.0) up to 5 years post-treatment. • Incidence, type and severity of serious adverse events up to 5 years post-treatment. • Physical examination, vital signs (blood pressure, heart rate, weight), 12-lead electrocardiogram (ECG) and laboratory tests including clinical chemistry, hematology and urinalysis up to 24 months. Physical examination, weight and laboratory tests also at the 36 months visit. • Annual CT scan (chest and abdomen) with radiocontrast up to 5 years post-treatment with a brief medical history. • To evaluate the potential development of edema at the donor site/limb, volume measurements of both legs will be performed (change from baseline and comparison to the unaffected/contralateral limb) up to 12 months. Pharmacological Endpoints • To assess the biodistribution (presence and titer) of Lymfactin® in blood up to 30 days and in wound secretion up to 5-7 days (until hospital discharge) through qPCR post-treatment. • To assess the presence and titer of anti-Lymfactin® antibodies in serum up to 12 months posttreatment. • To assess the concentration of VEGF-C in wound secretion up to 5-7 days (until hospital discharge) post-treatment. • To assess the systemic concentration of VEGF-C in serum up to 30 days post-treatment. Exploratory Study Endpoints • Newly developed MRI lymphangiography assessment and comparison of the correlation of the method to the already established lymphoscintigraphy in the assessment of lymphedema up to 24 months post-treatment. • PWC measurement of water content and edema in tissue by a sensitive, non-invasive device (MoistureMeterD Compact, Delfin Technologies) up to 24 months post-treatment.;Timepoint(s) of evaluation of this end point: as spesified | — |
Countries
Finland, Sweden
Contacts
Public ContactSponsor Study Contact
Herantis Pharma Plc
Outcome results
None listed