Study of Guanábana Leaves for The Treatment of Patients With Gastric, Gastroesophageal Junction, Pancreatic and Colorectal Adenocarcinomas; Hepatocellular Carcinoma, and Low Grade Lymphomas

NCT04773769 | Unknown

• 1 other identifier: CCAM 18-01
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Guanabana, known also as Graviola or Annona muricata is a tropical fruit which has been commonly used as complimentary/alternative medicine in Latin American countries. The main compounds in Graviola are the annonaceous acetogenins. These acetogenins have been shown to be selective and toxic against various types of cancer cells in-vitro and in-vivo experimental animal models. In spite of this evidence of anti tumor activity of Graviola, no prospective clinical studies have been carried out to determine if it also has clinical activity.The Investigator have observed two patients at Auxilio Mutuo Cancer Center who experienced significant tumor shrinkage while taking a tea made of Graviola leaves. Neither of these patients were taking any other treatment for their cancer. The investigator propose to conduct a study using guanabana leaves extract in patients with Gastroesophageal junction(GEJ) adenocarcinoma, as well as in Gastric adenocarcinoma, Hepatocellular carcinoma, Pancreatic adenocarcinoma, Low Grade Lymphomas and Colorectal adenocarcinoma.

Conditions

Gastric Adenocarcinoma; Adenocarcinoma of the Gastroesophageal Junction; Hepatocellular Carcinoma; Pancreatic Adenocarcinoma; Low Grade Lymphoma; Colorectal Adenocarcinoma

Outcome Measures

Primary Outcomes (3)

• RECIST criteria

  RECIST criteria will be used to measure response in solid tumors.

  Through study completion, an average of 3 years.

• Cheson criteria

  Cheson criteria will be used for lymphomas.

  Through study completion, an average of 3 years.

• Blood Counts

  Cases with Chronic Lymphocytic Leukemia will have their Complete Blood Counts monitored and the Absolute lymphocyte count will be followed for response.

  Through study completion, an average of 3 years.

Study Arms (1)

Overall Statistical design

EXPERIMENTAL

We will treat 9 patients of each tumor type with a tea made of Graviola Leaves. If no responses are observed then the trial will be closed for that particular histological type. Should a response occur, then the trial will continue to the second stage for that cell type until 24 patients are accrued. If 3 or more responses are observed out of 24 cases, then the result will be considered promising.

Dietary Supplement: Tea Made of Graviola Leaves

Interventions

Tea Made of Graviola Leaves DIETARY_SUPPLEMENT

Graviola leaves will be supplied to the patient with instructions on how to prepare the tea which will consist of 10 guanabana leaves which the patient will boil in 1 liter of water for 3 minutes. Once boiled, the formulation will be stores in the refrigerator and once cool enough the patient will start drinking 100 cc two times per day. The Treatment Period begins with Cycle 1 Day 1 dosing. Patients will take the tea continuously during a 28-day cycles, until there is an indication for treatment change based on response assessment.

Overall Statistical design

Eligibility Criteria

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

You may qualify if:

• Understand and voluntarily sign an informed consent form.
• Age \> 18 years at the time of signing the informed consent form.
• Willing and able to adhere to the study visit schedule and other protocol requirements.
• Must have measurable or evaluable disease.
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 2 weeks prior to treatment in this study.
• Performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale at study entry.

You may not qualify if:

• Patients actively taking guanabana or guanabana tea daily or who have used it at some point after their diagnosis of cancer.
• Patients with Parkinson's disease.
• Serum Total Bilirubin ≥ 3.0 mg/dL
• Serum Creatinine level ≥ 3.0 mg/dL
• Central Nervous System (CNS) involvement.
• Known human immunodeficiency virus (HIV) infection; Known active hepatitis B or hepatitis C infection.
• Females who are pregnant (positive urine test) or breast-feeding females.
• Any history of a medical condition or a concomitant medical condition that, in the opinion of the investigator, would compromise the subject's ability to safely complete the study.

Sponsors & Collaborators

• Auxilio Mutuo Cancer Center: lead

Study Sites (1)

Auxilio Mutuo Cancer Center

San Juan, 00918, Puerto Rico

RECRUITING

Related Publications (15)

• Chamcheu JC, Rady I, Chamcheu RN, Siddique AB, Bloch MB, Banang Mbeumi S, Babatunde AS, Uddin MB, Noubissi FK, Jurutka PW, Liu YY, Spiegelman VS, Whitfield GK, El Sayed KA. Graviola (Annona muricata) Exerts Anti-Proliferative, Anti-Clonogenic and Pro-Apoptotic Effects in Human Non-Melanoma Skin Cancer UW-BCC1 and A431 Cells In Vitro: Involvement of Hedgehog Signaling. Int J Mol Sci. 2018 Jun 16;19(6):1791. doi: 10.3390/ijms19061791.

  PMID: 29914183 BACKGROUND

• Deep G, Kumar R, Jain AK, Dhar D, Panigrahi GK, Hussain A, Agarwal C, El-Elimat T, Sica VP, Oberlies NH, Agarwal R. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity. Sci Rep. 2016 Mar 16;6:23135. doi: 10.1038/srep23135.

  PMID: 26979487 BACKGROUND

• Magadi VP, Ravi V, Arpitha A, Litha, Kumaraswamy K, Manjunath K. Evaluation of cytotoxicity of aqueous extract of Graviola leaves on squamous cell carcinoma cell-25 cell lines by 3-(4,5-dimethylthiazol-2-Yl) -2,5-diphenyltetrazolium bromide assay and determination of percentage of cell inhibition at G2M phase of cell cycle by flow cytometry: An in vitro study. Contemp Clin Dent. 2015 Oct-Dec;6(4):529-33. doi: 10.4103/0976-237X.169863.

  PMID: 26681860 BACKGROUND

• Paul J, Gnanam R, Jayadeepa RM, Arul L. Anti cancer activity on Graviola, an exciting medicinal plant extract vs various cancer cell lines and a detailed computational study on its potent anti-cancerous leads. Curr Top Med Chem. 2013;13(14):1666-73. doi: 10.2174/15680266113139990117.

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• Sun S, Liu J, Kadouh H, Sun X, Zhou K. Three new anti-proliferative Annonaceous acetogenins with mono-tetrahydrofuran ring from graviola fruit (Annona muricata). Bioorg Med Chem Lett. 2014 Jun 15;24(12):2773-6. doi: 10.1016/j.bmcl.2014.03.099. Epub 2014 Apr 18.

  PMID: 24780120 BACKGROUND

• Sun S, Liu J, Zhou N, Zhu W, Dou QP, Zhou K. Isolation of three new annonaceous acetogenins from Graviola fruit (Annona muricata) and their anti-proliferation on human prostate cancer cell PC-3. Bioorg Med Chem Lett. 2016 Sep 1;26(17):4382-5. doi: 10.1016/j.bmcl.2015.06.038. Epub 2015 Jun 25.

  PMID: 27499453 BACKGROUND

• Yang C, Gundala SR, Mukkavilli R, Vangala S, Reid MD, Aneja R. Synergistic interactions among flavonoids and acetogenins in Graviola (Annona muricata) leaves confer protection against prostate cancer. Carcinogenesis. 2015 Jun;36(6):656-65. doi: 10.1093/carcin/bgv046. Epub 2015 Apr 11.

  PMID: 25863125 BACKGROUND

• Torres MP, Rachagani S, Purohit V, Pandey P, Joshi S, Moore ED, Johansson SL, Singh PK, Ganti AK, Batra SK. Graviola: a novel promising natural-derived drug that inhibits tumorigenicity and metastasis of pancreatic cancer cells in vitro and in vivo through altering cell metabolism. Cancer Lett. 2012 Oct 1;323(1):29-40. doi: 10.1016/j.canlet.2012.03.031. Epub 2012 Apr 1.

  PMID: 22475682 BACKGROUND

• Li Y, Ye J, Chen Z, Wen J, Li F, Su P, Lin Y, Hu B, Wu D, Ning L, Xue Q, Gu H, Ning Y. Annonaceous acetogenins mediated up-regulation of Notch2 exerts growth inhibition in human gastric cancer cells in vitro. Oncotarget. 2017 Mar 28;8(13):21140-21152. doi: 10.18632/oncotarget.15502.

  PMID: 28416750 BACKGROUND

• Prabhakaran K, Ramasamy G, Doraisamy U, Mannu J, K R, Murugesan JR. Polyketide Natural Products, Acetogenins from Graviola (Annona muricata L), its Biochemical, Cytotoxic Activity and Various Analyses Through Computational and Bio-Programming Methods. Curr Pharm Des. 2016;22(34):5204-5210. doi: 10.2174/1381612822666160531163144.

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• Caparros-Lefebvre D, Elbaz A. Possible relation of atypical parkinsonism in the French West Indies with consumption of tropical plants: a case-control study. Caribbean Parkinsonism Study Group. Lancet. 1999 Jul 24;354(9175):281-6. doi: 10.1016/s0140-6736(98)10166-6.

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• Hollerhage M, Rosler TW, Berjas M, Luo R, Tran K, Richards KM, Sabaa-Srur AU, Maia JG, Moraes MR, Godoy HT, Hoglinger GU, Smith RE. Neurotoxicity of Dietary Supplements from Annonaceae Species. Int J Toxicol. 2015 Nov-Dec;34(6):543-50. doi: 10.1177/1091581815602252. Epub 2015 Sep 24.

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Related Links

• Graviola: A Systematic Review on Its Anticancer Properties

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Fernado Cabanillas, MD

  Hospital Español Auxilio Mutuo Inc.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fernando Cabanillas, MD

CONTACT

787-758-2000; cabanillasmd@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medicine Doctor/Medical Director

Study Record Dates

• First Submitted: December 4, 2018
• First Posted: February 26, 2021
• Study Start: November 7, 2018
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: February 26, 2021

Record last verified: 2021-02

Locations

PR (1)