Clinical trial NCT04138342: Topical Fluorescent Nanoparticles Conjugated Somatostatin Analog for Suppression and Bioimaging Breast Cancer
Official title: Fluorescent Nanoparticles Conjugated Long-acting Somatostatin Analog for Potent Suppression and Bioimaging Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Breast Cancer
Skin Cancer
Skin Diseases
Lead sponsor: Al-Azhar University
Sponsor class: OTHER
First posted: 2019-10-24
Enrollment: 30
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Breast cancer is a communal malignant disease between Saudi females, with a popularity of 21.8%. Since binding to somatostatin receptors (SSTR) induces no immunogenicity in vivo, somatostatin analog (veldoreotide) (VELD) may be suitable for delivering anti-cancer drugs to target and bioimaging the cancer cells. This work aimed to deliver CdS/ZnS core-shell type quantum dots with carboxylic acid-functionalized (QDs-COOH) which is bioimaging and anticancer nanoparticles decorated VELD as SSTR agonist with anti-cancer activity in the form of topical cream to be deposited deep in the breast periphery.

Detailed description: QDs-COOH will be conjugated to the N terminal of phenylalanine of VELD when the reaction proceeded at pH 7. Topical cream will be adapted to deliver the conjugated system for maximum deposition through breast cancer cells using emulsion technology. The formulated nanoparticles and cream will be characterized for size using dynamic light scattering, drug-polymer interaction using FTIR, and morphology using SEM. Cellular uptake, permeability and cell viability study of the successful system of interest will be studied in cell culture models using different breast cell lines. Moreover, the in vivo study will also proceed on rats induced breast cancer. Finally, the nanoparticles loaded in a topical cream will be applied with clinical trial approvement on the human breast cancer for bioimaging and treating breast cancer. This work is to present a novel formulation for treatment and bioimaging of breast cancer which can deliver safely to the patients in a high dose to the affected tumor cells.

Eligibility criteria: Inclusion Criteria:

1. Women, 25 to 60 years old.
2. Breast biopsy within 60 days of registration (dosing) without proof of aggressive cancer in any specimen;
3. Invasive breast cancer verified by histology of ER ≥ 10% (all test results should be checked and validated by the Pathology Department of the involved institution);
4. Participants performed traditional regional radical therapy (modified or moderate radical mastectomy) with or without neoadjuvant/adjuvant chemotherapy or radiotherapy;
5. Hemoglobin ≥ 90 g / L, neutrophils ≥ 1.5 × 109/L, platelets ≥ 75 × 109/L, AST and ALT ≤ 2.5 times the upper limit for natural (ULN), creatinine serum and urea nitrogen ≤ ULN.

Exclusion Criteria:

1. Patients have previously received any other treatment or have begun adjuvant therapy.
2. There are any comorbidities that may increase the level of sex hormones: pituitary adenomas, ovarian cancers, thymic carcinomas, etc.
3. There are any comorbidities that may decrease sex hormone rates such as hyperthyroidism, hypothyroidism, cirrhosis, extreme obesity, Turner syndrome, lack of sex hormone synthetase, intracranial tumors, pituitary atrophy, etc. Patients have undergone and expected suppression of ovariectomy and ovarian activity.
4. Patients have been diagnosed with other test drugs for the next 2 months.
5. People of child-bearing age who are not willing to take effective contraception through therapy. Serious non-maligned tumor comorbidities can impair long-term follow-up.
6. Patients have a family history of endometrial, reproductive or other gynecological malignancies. Transvaginal testing indicated more severe ovary defects and endometrial thickening.
7. Patients had thrombotic incidents such as a cerebrovascular injury (including a transient ischemic attack), deep venous thrombosis, and pulmonary embolism within 6 months of the start of the research.
8. Serious insufficiency of the liver with Child-Pugh C class. Serious heart disease of New York Heart Association (NYHA) class ≥III. Patients are considered to be severely allergic to medications.
9. Patients have a record of other malignancies over the last five years, with the exception of cutaneous basal cell carcinoma and cervical in situ carcinoma that has been healed. In other instances, investigators do not feel the topics are acceptable for study participants.
10. Pregnant or lactating women (women of childbearing age should receive a negative pregnancy test within 14 days of the first dosage or, if pregnant, clinicians are required to undergo an ultrasound review to exclude childbirth).

Primary outcomes:
measure: Growth inhibition was measured using the sulforhodamine B-based assay.
timeFrame: 6 months
measure: Amount of QDs-VELD fluorescent QDs-VELD in the breast periphery due to the fluorescence of QDs using flow cytometry.
timeFrame: 6 months
measure: Growth inhibition was measured by visual determination of breast cancer cells.
timeFrame: 6 months
Secondary outcomes:
measure: Stable topical quantum dots coated veldoreotide
timeFrame: three months
Other outcomes:
Locations:
city: Assiut
country: Egypt
facility: Assiut Clinic
city: Buraidah
country: Saudi Arabia
facility: Buraidah Clinic
state: Al Qassim
city: Buraidah
country: Saudi Arabia
facility: Faculty of Pharmacy
state: Qassim
city: Buraidah
country: Saudi Arabia
facility: Pharmaceutics dept., Faculty of Pharmacy, Qassim University
state: Qassim
Study officials:
affiliation: Qassim University
name: Ahmed AH Abdellatif, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Clive S, Gardiner J, Leonard RC. Miltefosine as a topical treatment for cutaneous metastases in breast carcinoma. Cancer Chemother Pharmacol. 1999;44 Suppl:S29-30. doi: 10.1007/s002800051114.
citation: Doroshow JH. Redox modulation of chemotherapy-induced tumor cell killing and normal tissue toxicity. J Natl Cancer Inst. 2006 Feb 15;98(4):223-5. doi: 10.1093/jnci/djj065. No abstract available.