Safety and Efficacy Evaluation of the P2Et Extract in Patients With Breast Cancer

NCT05007444 | Unknown Phase 2

• 1 other identifier: CS003-BC
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, the study of many extracts in different types of cancer has allowed the validation of scientific knowledge either as a therapy that reduces the size of the tumor or that helps to improve the quality of life of the patient by reducing the associated effects of the treatment. In the Immunobiology and Cell Biology group of the Pontificia Universidad Javeriana, a standardized extract of Caesalpinia spinosa (Dividivi) called P2Et has been obtained. This extract has been shown to have cytotoxic activity in different human and murine tumor cell lines, favoring the induction of immunogenic cell death with the release of danger signals such as calreticulin, HMGB1 and ATP. Additionally, treating mice with murine melanoma and sinus tumors significantly reduces tumor size and metastases. On the other hand, induction of complete autophagic flux and synergistic effects with anthracycline-type chemotherapeutics have been shown in human cell lines and in animal models of breast cancer. With this background, and the results of the Phase I clinical study carried out in healthy volunteers that showed that the extract is safe, the investigators propose that treatment with the P2Et extract in patients with breast cancer could improve their general condition, impacting their quality of life. , and induce antitumor immune response, improving the immune infiltrate and acting as a transforming agent from a cold tumor to a warm tumor. This would lead to an improvement in the long-term survival of patients treated with the phytomedicine in conjunction with the chemotherapeutic treatment selected by the treating oncologist. In order to advance on this path, and responding to the adjustments suggested in the phase I study in healthy individuals, it is proposed to carry out a clinical study that allows determining the optimal biological dose of the P2Et extract in a design based on randomized simulations of adaptive form and considering the safety of the extract as an objective in patients with breast cancer. Additionally, those parameters that allow defining the best indicators of effectiveness of P2Et in this group of patients will be evaluated, such as modulation of the immune response, quality of life, reduction of adverse effects and progression-free survival.

Conditions

Breast Cancer; Quality of Life; Tumor, Breast

Outcome Measures

Primary Outcomes (1)

• Toxicological profile

  Determination of the optimal Biological Dose according to the toxicological profile

  18 months

Secondary Outcomes (4)

• Clinical and pathological response in the tumor of the patients

  18 months

• Survival

  24 months

• Quality of life in breast cancer patients

  24 months

• Adverse events

  18 months

Study Arms (2)

Placebo comparator

PLACEBO COMPARATOR

Patients in the placebo group will receive the stable daily dose divided into 2 doses with meals of the optimal biological dose determined in stage I every 12 hours for the duration of standard therapy. The patient will self-administer the phytomedicine until completing the established treatment days. The taking of the phytomedicine will only be suspended 3 days before each cycle of standard therapy and will restart 3 days after having passed the cycle. That is, in the anthracycline and cyclophosphamide (AC) phase, the patient will start taking the phytomedicine 3 days after having received their standard chemotherapy cycle and will suspend it 3 days before the next cycle begins. For the taxane phase, the patient will take the P2Et without suspension during the treatment cycles.

Drug: Placebo

Active comparator P2Et

ACTIVE COMPARATOR

Patients in the P2Et group will receive the stable daily dose divided into 2 doses with meals of the optimal biological dose determined in stage I every 12 hours for the duration of standard therapy. The patient will self-administer the phytomedicine until completing the established treatment days. The taking of the phytomedicine will only be suspended 3 days before each cycle of standard therapy and will restart 3 days after having passed the cycle. That is, in the anthracycline and cyclophosphamide (AC) phase, the patient will start taking the phytomedicine 3 days after having received their standard chemotherapy cycle and will suspend it 3 days before the next cycle begins. For the taxane phase, the patient will take the P2Et without suspension during the treatment cycles.

Drug: P2Et (Caesalpinia spinosa extract)

Interventions

P2Et (Caesalpinia spinosa extract) DRUG

Patients who meet inclusion criteria will begin taking 4000mg daily, distributed in 2 doses with meals of 2000mg of P2Et extract during neoadjuvant treatment. In case of presenting toxicity, it will be lowered to the next dose level, that is, 2000 mg under the same dosage schedule and 1000 mg following the same principle. The taking of the phytomedicine will only be suspended 3 days before each cycle of standard neoadjuvant therapy and will restart 3 days after having passed the cycle. That is, in the anthracyclines and cyclophosphamide (AC) phase, the patient will start taking the phytomedicine 3 days after having received their standard chemotherapy cycle and will suspend it 3 days after the next cycle begins. For the taxane phase, the patient will take the P2Et without suspension during the treatment cycles.

Active comparator P2Et

Placebo DRUG

After determining the optimal biological dose (OBD), the patients will be divided into the placebo arm or the treatment arm. In the anthracyclines and cyclophosphamide (AC) phase, the patient will start taking according to the asignation as stated in the drug intervention.

Placebo comparator

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult women over 18 years of age.
• Patients with a diagnosis of histopathologically confirmed stage II-III invasive breast cancer who are candidates for treatment with standard neoadjuvant chemotherapy.
• Documented results of the status of estrogen receptors (ER), progesterone (RP), KI 67, and epidermal growth factor receptor 2 (HER-2).
• Patients eligible for neoadjuvant treatment with AC (Doxorubicin / cyclophosphamide) every 2 or 3 weeks followed by taxanes (paclitaxel for 12 weeks or docetaxel every 3 weeks for 4 cycles)
• ECOG scale status from 0 to 1 with survival greater than 3 months.
• Subject is able to swallow and retain oral medication and does not have uncontrolled emesis or persistent diarrhea.
• Adequate renal, hematological, and hepatic function at the discretion of the investigator.
• No uncontrolled or significant comorbidities determined by medical history, physical examination and screening laboratories at the discretion of the investigator. (Leukocytes greater than 2000 / mm3, neutrophils greater than 1500 / mm3, hemoglobin greater than 9 g / dl, creatinine less than 1.5 times the upper limit, transaminases less than 3 times the upper limit, bilirubin less than 1.5 times the upper limit).
• Patients of childbearing age and without safe non-hormonal planning methods should have a negative pregnancy test before screening and each treatment cycle.
• Fertile female subjects (those who are not postmenopausal for at least 12 months or are surgically sterile by bilateral tubal ligation, bilateral oophorectomy or hysterectomy) and their male partners, must use at least one of the contraceptive methods that are listed below during study entry, throughout the study, and for at least 6 months after use of the P2Et extract (the effects of the P2Et extract on the developing human fetus are unknown):
• to. Complete abstinence from sexual intercourse, beginning at least one complete menstrual cycle before administration of study drug; (It should be noted: sexual abstinence as a contraceptive method should be limited to those cases in which it is already established as the choice of the patient's pre-existing lifestyle).
• b. Vasectomy in the partner of a female subject c. Intrauterine device (IUD) d. Double barrier method (condom, contraceptive sponge, diaphragm or vaginal ring with jelly or spermicidal cream).
• k) Desire to complete the study and follow-up interventions.

You may not qualify if:

• Subjects treated in any other clinical therapeutic protocol in the 30 days prior to study entry or during study participation.
• Patients who are receiving other agents under investigation.
• History of allergic reactions attributed to polyphenol-type compounds similar to those found in green tea.
• The subject is a pregnant or breastfeeding woman.
• Patients who due to their clinical condition should receive anti-HER2 antibodies
• Concomitant severe morbidity, active at the discretion of the investigator
• Subjects with malabsorption syndrome or another condition that affects the enteral route of administration
• Subjects with confirmed HIV diagnosis prior to enrollment or HIV positive diagnosis at the time of screening.
• Solid organ transplant recipients or hematopoietic component.
• The use of other phytomedicines, vitamins or herbal supplements must have been suspended at least one week before entering the study.
• Previous malignant disease active within the previous 3 years, except for locally curable cancers that have apparently been cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or mother
• Any condition that at the discretion of the principal investigator renders the subject ineligible to participate in this study

Sponsors & Collaborators

• Hospital Universitario San Ignacio: lead
• Pontificia Universidad Javeriana: collaborator

Study Sites (1)

Pontificia Universidad Javeriana

Bogotá, 110221, Colombia

RECRUITING

Related Publications (7)

• Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, Bonaventure A, Valkov M, Johnson CJ, Esteve J, Ogunbiyi OJ, Azevedo E Silva G, Chen WQ, Eser S, Engholm G, Stiller CA, Monnereau A, Woods RR, Visser O, Lim GH, Aitken J, Weir HK, Coleman MP; CONCORD Working Group. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018 Mar 17;391(10125):1023-1075. doi: 10.1016/S0140-6736(17)33326-3. Epub 2018 Jan 31.

  PMID: 29395269 BACKGROUND

• Bardia A, Baselga J. Neoadjuvant therapy as a platform for drug development and approval in breast cancer. Clin Cancer Res. 2013 Dec 1;19(23):6360-70. doi: 10.1158/1078-0432.CCR-13-0916.

  PMID: 24298066 BACKGROUND

• Bayet-Robert M, Kwiatkowski F, Leheurteur M, Gachon F, Planchat E, Abrial C, Mouret-Reynier MA, Durando X, Barthomeuf C, Chollet P. Phase I dose escalation trial of docetaxel plus curcumin in patients with advanced and metastatic breast cancer. Cancer Biol Ther. 2010 Jan;9(1):8-14. doi: 10.4161/cbt.9.1.10392. Epub 2010 Jan 21.

  PMID: 19901561 BACKGROUND

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res. 1970;13:1-27. doi: 10.1159/000386035. No abstract available.

  PMID: 4921480 BACKGROUND

• Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, Earl HM, Poole CJ, Hiller L, Dunn JA, Bowden SJ, Twelves C, Bartlett JM, Mahmoud SM, Rakha E, Ellis IO, Liu S, Gao D, Nielsen TO, Pharoah PD, Caldas C. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014 Aug;25(8):1536-43. doi: 10.1093/annonc/mdu191. Epub 2014 Jun 9.

  PMID: 24915873 RESULT

• Ballesteros-Ramirez R, Pinilla P, Sanchez J, Torregrosa L, Aschner P, Uruena C, Fiorentino S. Safety and efficacy of P2Et extract from Caesalpinia spinosa in breast cancer patients: study protocol for a randomized double blind phase II clinical trial (CS003-BC). BMC Complement Med Ther. 2023 Sep 5;23(1):309. doi: 10.1186/s12906-023-04139-w.

  PMID: 37670337 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study is a design based on adaptive randomized simulations (BOIN12) (Zhou, Lee, \& Yuan, 2019). Each of the patients included in the different groups will undergo the analysis of the immune response parameters described in Annex 1. With the optimal biological dose calculated in stage 1, it will go to stage 2 where 40 randomized breast cancer patients will be enrolled in treatment with the P2Et extract or placebo. In these patients, parameters related to the immune response, progression-free survival, quality of life and tumor reduction will be evaluated.

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 16, 2021
• Study Start: March 1, 2022
• Primary Completion: June 1, 2023
• Study Completion: June 30, 2023
• Last Updated: August 9, 2022

Record last verified: 2022-08

Locations

CO (1)