Evaluation of the Safety and Efficacy of Esperanza Extract (PA001)

Study Overview
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Brief Summary
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This is a phase Ib/II clinical study that has two phases. In phase Ib, the safety evaluation of the extract of Petiveria alliacea (Esperanza) will be carried out in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and biliary tract) and patients with newly diagnosed and relapsed acute leukemia. In phase IIb, the safety will continue to be evaluated, and the efficacy of the Esperanza extract will be explored in combination with chemotherapy in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and biliary tract) with newly diagnosed acute leukemias and relapses.

Detailed Description
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Anamú, Petiveria alliacea, has been used by traditional medicine to treat leukemia and breast cancer. However, its activity on tumor metabolism makes it a therapeutic candidate for many tumors with alterations in glycolytic metabolism, but also uses the mitochondria to produce energy. Given the glycolytic nature of some tumor cells, the modulating activity of cell metabolism exerted by anamú extract may be partly responsible for the anti-tumor activity. Previous reports show that some patients with ALL or AML whose response to treatment was evaluated in vitro are sensitive to a standardized extract of Petiveria alliacea. Even more interesting is the fact that when we treat the cells with allopathic therapy, explicitly established for each of these pathologies, the sensitivity of the blasts increases when they are treated concomitantly with the extract, which suggests that the intrinsic resistance of each one of tumor cells in the different tissues evaluated can be reduced by the action of the phytomedicine. The same thing was observed when spheres obtained from human breast cancer were co-treated with the anamú extract and anthracyclines. These observations allow to validate the traditional use of anamú in the treatment of some tumors, such as leukemia and breast cancer, among others. However, to observe the safety and effects on patients, it is necessary to develop a clinical study that would allow the anamú phytomedicine produced in the appropriate pharmaceutical conditions, to be included as a complementary therapy based on a standardized extract of the plant and that can overcome the resistance of tumor cells to conventional treatments, improving response and increasing overall survival of patients in Colombia. Although the explosion of new therapies in solid tumors and hematological alterations is not so high, countries such as Germany, France, and Italy have used traditional medicine from which herbal pharmaceutical preparations are derived in the treatment of different types of diseases, including cancer. , estimating the use of these products between 30 and 75% of patients worldwide. These herbal products are mainly used to reduce allopathic therapies' side effects and organic toxicity, protect and stimulate the immune system, or prevent future neoplasms or their recurrence. Currently, various extracts from natural products are in clinical trials in the United States, and there is significant evidence about some plants' role in leukemia's evolution. This is a phase Ib/II clinical study that has two phases. In phase Ib, the safety evaluation of the extract of Petiveria alliacea (Esperanza) will be carried out in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and biliary tract) and patients with newly diagnosed and relapsed acute leukemia. In phase IIb, the safety will continue to be evaluated, and the efficacy of the Esperanza extract will be explored in combination with chemotherapy in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and biliary tract) with newly diagnosed acute leukemias and relapses.

Official Title
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Evaluation of the Safety and Efficacy of Esperanza Extract (Petiveria Alliacea) in Patients With Metastatic Gastrointestinal Tumors and Acute Leukemia

Conditions
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Acute Leukemia, Neoplasm, Stomach, Gastric Neoplasms Malignant, Pancreatic Neoplasms, Colorectal Neoplasms, Acute Leukemia in Relapse, Acute Leukemia Lymphoid, Acute Myeloid Leukemia, Acute Myeloid Leukemia, in Relapse

Intervention / Treatment
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* Drug: Petiveria Alliacea Preparation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Solid Tumors: Patients must be over 18 years of age, with no upper age limit Histological diagnosis of gastrointestinal cancer may include stomach, colon, bile ducts, and pancreas. Measurable disease through diagnostic tests and who will receive chemotherapy as primary treatment for their disease. At least one discrete metastatic site identified ECOG scale status from 0 to 2 with survival more significant than two months. Subject can swallow and retain oral medication and does not have uncontrolled emesis or persistent diarrhea. Adequate renal, hematological, hepatic, and cardiac function at the investigator's discretion. Without uncontrolled or significant comorbidities determined by clinical history, physical examination, and screening laboratories at the investigator's discretion. Patients of childbearing age and without safe non-hormonal planning methods must have a negative pregnancy test before the screening. Fertile female subjects (those who have not been 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 listed below during study entry, throughout the study, and for at least six months after use of the P2Et extract (the effects of the P2Et extract on the developing human fetus are unknown): a. 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 where it is already established as the patient's pre-existing lifestyle choice). 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 spermicidal jelly or cream). k) Desire to complete the study and follow-up interventions. Inclusion Criteria Acute Leukemia: Patients must be over 18 years of age, with no upper age limit Patients who have had a new diagnosis of acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) will be eligible for the study and are eligible for chemotherapy treatment. Patients must be newly diagnosed Patients must have failed initial therapy, which may manifest in any of the following ways: Demonstration of primary refractory disease (primary induction failure) as evidenced by mid-cycle bone marrow analysis showing lack of complete tumor clearance (CTC). Relapse of the initial disease after a period of achieving complete remission. Subject can swallow and retain oral medication and does not have uncontrolled emesis or persistent diarrhea. Adequate renal, hematological, and hepatic function at the investigator's discretion. Without uncontrolled or significant comorbidities determined by clinical history, physical examination, and screening laboratories at the investigator's discretion. Patients of childbearing age and without safe non-hormonal planning, methods must have a negative pregnancy test before the screening. Fertile female subjects (those who have not been 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 listed below. Listed below during study entry, throughout the study, and for at least six months after use of the P2Et extract (the effects of the P2Et extract on the developing human fetus are unknown): a. 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 where it is already established as the patient's pre-existing lifestyle choice). 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 spermicidal jelly or cream). h) Desire to complete the study and follow-up interventions. Exclusion Criteria: The exclusion criteria apply to solid tumors as well as hematological tumors. Subjects with one or more conditions are not eligible for this study. Subjects treated in any other therapeutic clinical protocol 30 days prior to study entry or during study participation. Patients receiving other investigational agents. The female subject is pregnant or nursing. A negative serum or urine pregnancy test obtained at screening should confirm that the woman is not pregnant. Pregnancy tests are not required for postmenopausal or surgically sterilized women. Serious concomitant morbidity, active at the discretion of the investigator Subjects with a confirmed diagnosis of HIV before enrollment or a positive diagnosis of HIV at the time of screening. Recipients of solid organ transplants. Any condition that, in the opinion of the principal investigator, makes the subject ineligible to participate in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: This is a phase Ib/II clinical study that has two phases. In phase Ib, the safety evaluation of the extract of Petiveria alliacea (Esperanza) will be carried out in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach and biliary tract) and patients with newly diagnosed and relapsed acute leukemia. In phase IIb, the safety will continue to be evaluated and the efficacy of the Esperanza extract will be explored in combination with chemotherapy in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach and biliary tract) and patients with newly diagnosed acute leukemias and relapses
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metastatic gastrointestinal tumors and acute leukemia patients<br>Patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and bile ducts) and newly diagnosed/relapse acute leukemias who meet the inclusion criteria will take the anamu extract with chemotherapy to evaluate the adverse drug-related side effects. | Drug: Petiveria Alliacea Preparation<br>* Petiveria Alliacea Preparation in pill<br>|
| Experimental: Stage II Metastatic gastrointestinal tumors including pancreas<br>For solid metastatic tumors, 30 patients will be recruited, which can be from the colon, pancreas, stomach, and bile ducts, divided into two groups of 15 patients, an intervention group and a placebo group. The intervention group will receive the Esperanza extract at DMT for three continuous treatment cycles (approximately 12 weeks), and the other group will receive the placebo. | Drug: Petiveria Alliacea Preparation<br>* Petiveria Alliacea Preparation in pill<br>|
| Placebo Comparator: Stage II Placebo Metastatic gastrointestinal tumors including pancreas<br>For solid metastatic tumors, 30 patients will be recruited, which can be from the colon, pancreas, stomach, and bile ducts, divided into two groups of 15 patients, an intervention group and a placebo group. The intervention group will receive the Esperanza extract at DMT for three continuous treatment cycles (approximately 12 weeks), and the other group will receive the placebo. Both groups will receive standard chemotherapy treatment for their underlying disease. The safety evaluation will be carried out in each treatment cycle, and the efficacy evaluation will be carried out at the end of the three cycles. | Drug: Placebo<br>* Placebo in pill<br>|
| Experimental: Acute leukemia (Newly/Relapse)<br>For newly diagnosed hematological tumors, 28 patients will be recruited and will receive the Esperanza extract at DMT. The intervention group will continuously receive the Esperanza extract at DMT for four weeks with the standard chemotherapy regimen for their underlying disease. The safety and efficacy evaluation will be carried out at the end of the treatment cycle. Patients with relapsed or refractory acute leukemias will be admitted to receive the calculated DMT in phase Ib; A total of 6 patients will be recruited, and safety and efficacy evaluations will be performed during three treatment cycles or progression and death of the patient. For the analysis of the response in patients with acute leukemia, a comparison will be made with a group followed historically. A propensity score matching will be performed for statistical analysis in case of differences in their baseline characteristics. | Drug: Petiveria Alliacea Preparation<br>* Petiveria Alliacea Preparation in pill<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and efficacy | Evaluate the adverse drug reactions of cancer patients treated with anamú extract and chemotherapy through the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life in patients | Changes of at least 5 points above the difference between the groups of the functional scales of the patients evaluated using the EORTC QLQ-C-30 scale | 12 months | 
| Tumor response | To determine the impact of treatment with Esperanza extract in combination with chemotherapy on the number and size of metastases. | 12 months | 
| Survival | To determine event/progression-free survival in patients with metastatic gastrointestinal tumors (colon, pancreas, stomach, and bile ducts) and patients with newly diagnosed and relapsed acute leukemias. | 12 months |