TITLE: Phase I Randomized Study of Jatyadi Oil Enema for Preventing or Reducing the Severity of Radiotherapy-Induced bleeding P/R or Piles in Patients With Anal or Rectal Cancer, cervical cancer or any pelvic tumor. Cancer is a latin word means a crab. Cancer incidence:.
TITLE:Phase I Randomized Study of Jatyadi Oil Enema for Preventing or Reducing the Severity of Radiotherapy-Induced bleeding P/R or Piles in Patients With Anal or Rectal Cancer, cervical cancer or any pelvic tumor.
Atharva Ayurveda Hospital
and cancer research center.
OBJECTIVESPrimaryDetermine the ability of Jatyadi oil enema to prevent the incidence of severe or life-threatening radiotherapy-induced bleeding P/R and piles in patients with anal or rectal cancer.SecondaryCompare the quality of life of patients treated with this drug vs placebo. Compare treatment delays and/or dose reductions (radiotherapy) in patients treated with these drugs.
2 Modified Jatyadi Oil - Background and Therapeutic RationaleThe Ayurvedic Formulary of India Part I, Govt. of India, Ministry of Health and Family Planning Department of Health. Jatyadi Taila ( Ref: Sarangdhara Samhita, Madhyamkhand, Adhyaya 9/168-170)No. Name (part) Botanical name Proportion 1.Jati pallava(Lf.) Jasminum officinale 1 part 2.Nimba pallava (Lf.) Azadirachta indica 1 part 3.Patola pallava (Lf.) Trichosanthes dioica 1 part 4.Naktamala pallava(Lf.) Pongamia pinnata 1 part 5.Siktha(bee wax) Bee wax 1 part 6.Yastimadhu (Rt.) Glycyrrhiza glabra 1 part 7.Kushtha (Rt.) Saussuria lappa 1 part 8.Haridra(Rz.) Curcuma longa 1 part 9.Daru haridra(St.) Berberis aristata 1 part10 Katurohini (Rz.) Picrorhiza kurroa 1 part11 Manjishtha (Rz.) Rubia cordifola 1 part 12 Padmaka (Ht. Wd.) Prunus cerasoides 1 part13 Lodhra (St.Bk.) Symplocos racemosa 1 part14 Abhaya (Ft. P.) Terminalia chebula 1 part15 Nilotpala (Fl.) Nymphaea stellata 1 part16 Tutthaka Copper sulphate 1 part 17 Sariva (Rt.) Hemidesmus indicus 1 part18 Naktamala bija (Sd.) Pongamia pinnata 1 part19 Kumari Aloe Barbadensis 1 part20 Punarnava Boerhaavia Diffusa 1 part21 Nagkeshar Mesua Ferrea 1 part22 Haritaki Terminalia Chebula 1 part23 Aswagandha Withenia Somnifera 1 part 24 Taila Sesamum indicum seeds 72 parts 25 Water 288 parts
ENTRY CRITERIADisease Characteristics:Histologically confirmed primary Anal or Rectal Cancer, cervical cancer or any pelvic tumor.Must be scheduled to receive radiotherapyPrior/Concurrent Therapy:Biologic therapyNot specifiedEndocrine therapyNot SpecifiedNo prior pelvic radiotherapy .No prior intensity-modulated radiotherapy No brachytherapy prior to or after completion of all external beam radiotherapy
SurgeryNo prior abdominal-perineal resection or other surgical procedure leaving the patient without a functioning rectum No colostomyOtherMore than 30 days since other prior investigational drugs No prior treatment for cancer therapy-related bleeding P/R or piles. No concurrent prophylactic bleeding P/R or piles medicationAge 18 and overPerformance statusNot specifiedLife expectancyNot specifiedHematopoieticNot specified
RenalNot specifiedGastrointestinalNo prior chronic or acute regional enteritis No malabsorption syndrome No prior inflammatory bowel disease that may exacerbate the radiotherapy toxicity No grade 2 or greater uncontrollable diarrhea at baseline No prior cholecystitis or gallstones, unless a cholecystectomy has been performed No prior incontinence of stoolOtherNot pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No uncontrolled diabetes (e.g., fasting glucose > 250 mg/dL) No prior allergy or hypersensitivity to study drug or other related drug or compound
Study Design OverviewPresent study is to evaluate the efficacy and tolerability of Medicated Enema 30 ml./day before exetarnal radiation for Preventing or Reducing the Severity of radiotherapy-Induced bleeding P/R or Piles, skin reactions, constipation etc in Patients With Anal or colorectal Cancer, cervical cancer or any pelvic tumor.A fixed schedule of randomization will assign equal numbers of patients to each treatment arm.Eligible patients will take either modified Jatyadi oil enema before Radiotherapy or standard symptomatic treatment for side effects. Clinical and laboratory parameters will be assessed to evaluate disease response and tolerability of treatment
Arm I: Patients receive anyallopathic medicines when the start of bleeding P/R OR piles during Radiotherapy.Arm II: Patients receive Jatyadi oil enema for 20/days during Radiotherapy induced bleeding P/R or piles.
In both arms, treatment continues in the absence of unacceptable toxicity.Quality of life is assessed at baseline, at the completion of radiotherapy, and at 3 and 6 months from the start of chemotherapy.Patients are followed at 3 to 6 months from the start of chemotherapy.
Dosing SchedulesPatients will be randomized to one of two treatment arms:The Matra Basti i.e. enema treatment will be performed for 5 weeks along with chemotherapy, with follow-up observation for 1 month.During the study, patients will be divided in two equal groups.Group A will receive 30ML Medicated enema of Ayurvedic oil preparation consisting of modified Jatyadi Tail (oil) Group B will receive only the symptomatic aloapathy treatment.
Efficacy ParametersPrimary: Response rate and time to manage side effects of chemotherapy. Secondary: Response duration and patient survival.Effects of treatment on patients' quality of life measured by the EORTC QLQ
Safety ParametersQualitative tolerability and any quantitative toxicities of study medications will be evaluated. While there is no single universally fitting prescription for cancer treatment in Ayurveda, work of attentive physicians during the millennia has identified powerful anti-cancer herbs and wound healing herbs that have the potential of treating colorectal bleeding. These herbal medicinal can be successfully delivered through the oil enemas to the affected site. The oil itself serves both as a vehicle and as a medicinal treatment that promotes wound healing and re-sealing of the ruptured epithelial layer of the colon and rectum.
4 Clinical StudiesA Phase I study of modified Jatyadi oil enema along with Standard Radiotherapy in any pelvic tumor was conducted by the ACC in 20 patients. Of these patients, 14 patients had very less side effects of Radiotherapy in compare to other patients. The present treatment also improves the quality of the life of patient.These preclinical data suggest that Modified Jatyadi oil could be active even at any stages..
Exclusion CriteriaThe exclusion criteria for this study are: Known hypersensitivity to Radiotherapy. Patients with life threatning side effects.Unco-operative patients can be withdrowal from the study.
Outline of Study ProceeduresPatients will be screened prior to receiving study medication to determine eligibility for entry into the study. Eligible patients will be randomized to receive a Jatyadi oil enema 30 ml./day before exetarnal Radiotherapy in Pelvic area for 3 weeks.Patients will be evaluated every week..
Study EvaluationsThe following evaluations will be performed at every scheduled daily visit:Interim history.Complete physical examination including weight and performance status.Assessment of treatment tolerability/toxicity.The Quality of Life questionnaire, EORTC QL also should be completed at scheduled visits every week as long as the patient remains on study. Diagnostic imaging studies for complete disease/response assessment will be performed.
Diagnostic imaging studies for complete disease/response assessmentwill be performed.a specified study visits every month the investigator will record the current response for the patient, that is, complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). When possible, the same physician will evaluate the patient's response at each visit..
Follow-Up and Evaluation of Response/ResponseDurationAt the completion of the study for each patient the investigator will assess that patient's evaluability and characterize their best overall response by WHO criteria (Complete Response, Partial Response, Stable Disease or Progression). All patients will be followed at regular intervals .
Assessment Of Toxicity Gradereport the toxicity grade using the following criteria.Grade 1 = Mild, an adverse experience which is easily tolerated by the patient, causing minimal discomfort and not interfering with everyday activities.Grade 2 = Moderate, an adverse experience which is sufficiently discomforting to interfere with normal everyday activities.Grade 3 = Severe, an adverse experience which prevents normal everyday activities.Grade 4 = Life Threatening, an adverse experience which places the patient at immediate risk of death.
Outcomes Measurement and AnalysisQuality of life will be assessed using the EORTC QLQ-C30 (Version 2.0). The questionnaire consists of the items which assess the impact of the disease and of treatment on the patient's daily activities. The analysis of the quality of life data will comprise comparisons of the change in scores over time (longitudinal change) and overall QOL scores for each of the two treatment groups
Administrative MattersTo comply with Good Clinical Practice, important administrative obligations relating to investigator responsibilities, monitoring, archiving data, audits, confidentiality and publications must be fulfilled.
APPENDIX BNCIC CTG EXPANDED COMMON TOXICTTY CRITERIA* Denotes NCTC CTG specific criteria. Any toxicity which causes death should be given grade 5GRADEo 11234ALLERGYALLER Allergynonetransient rash, fever <38°c, 100.4TUrticaria, fever^38°c, 100.4°F, mild bronchospasmserum sickness, bronchospasm, req parenteral medsanaphylaxisFever felt to be caused bv drug allergy should be coded as ALLERGY f AL LER). Non allergic drug fever (eg. as from biologies') should be coded under ELU-UKE SYMPTOMS (FL EEV). If fever is due to infection, code INFECTION only (IN FEC 01 IN NEU).NB: Protocols requiring detailed reporting of hvpersensinvity reactions, will include a Hypersensitivity Reaction module.AL OTH Other *none jMildModerateseverelife thp*?^»»njKgBLOOD/BONE MARROW (SI UNITS)BL WBC White Blood Count (WBC)24.0 10*/L3.0-3.92.0-2.91.0-1.9<1.0BLPLT PlateletsWNL VflL75-0-normal50.0-74.925.0-49.9<25.0BLHGB Hemoglobin (Hgb)WNL g/L100-nonnal80-9965-79<65BLGRAGrannlocytes (i.e nents + bands)22.0 \<PlL1.5-1.91.0-1.405-0.9<0.5BLLYM Lymphocytes22.0 10/L1.5-1.91.0-1.405-0.9<0.5BLHEM Hemorrhage resulting from thrombocytopenia [clinical)nonemild, do transfusion (includes bruiseyheinatoma, petechiae)gross, 1-2 units transfusion per episodegross, 3-4 units transfusion per episodemassive, >4 units transfusion per episodeBL OTH other*noneMildmoderateseverelife threateningCANCER RELATED SYMPTOMSCA DEA Death from malignantDisease within 30 days of treatment * (grade =5)CAPAI Cancer pain*nonepain, but no treatment leqpain controlled with non-opioidspain controlled with opioidsuncontrollable painCA SEC Second malignancy *none—present—CAOTH*noneMildmoderateseverelife threateningCARDIOVASCULARCD ART Arterial* (non my ocar dial)none"*transient events (eg. transient ischemia attack)permanent event (eg. cerebral vascular accident)CD VEN Venous*noneSuperficial (excludes IV site reaction -code SK LTD)deep vein thrombosis not req anticoagulant therapydeep vein thrombosis req anticoagulant therapypulmonary embolismCDDYS DysrhythmiasnoneAsymptomatic, transient, req no therapyrecurrent or persistent, req no therapyreq therapyreq monitoring, or hypotension, or ventricular tachycardia, or fibrillation
References:Alberts DS, Martinez ME, et al, and the Phoenix Colon Cancer PreventionPhysicians' Network: Lack of effect of a high-fiber cereal supplement on therecurrence of colorectal adenomas. New England Journal of Medicine 342(16):1156-1162, 2000.Augustsson K, Skog K, Jagerstad M, et al.: Dietary heterocyclic amines andheterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population study. and kidney: a population-based study.Lancet 353(9154): 703-707, 1999.Bjelke E: Epidemiology of colorectal cancer, with emphasis on diet.Cancer Causes and Control 2(5): 325-357, 1991.Cancer Causes and Control 2(6): 427-442, 1991.cancer of the colon, rectum, bladder, and kidney: a population-based study.Cheah PY: Hypotheses for the etiology of colorectal cancer--an overview.consumption. Cancer 58(11): 2363-2371, 1986.Hirayama T, Tannenbaum SR, Reddy BS, et al.: A large-scale cohort study onthe relationship between diet and selected cancers of the digestive organs.Banbury Report 7: 409-429, 1981.Hirayama T, Tannenbaum SR, Reddy BS, et al.: A large-scale cohort study onin Cancer. New York: Marcel Dekker, 1992, pp 55-84.
Kampman E, Giovannucci E, van't Veer P, et al.: Calcium, vitamin D, dairyfoods, and the occurrence of colorectal adenomas among men and women in twoprospective studies. American Journal of Epidemiology 139(1): 16-29, 1994.Kritchevsky D: Dietary guidelines: the rationale for intervention. CancerLack of effect of a low-fat, high-fiber diet on the recurrence of colorectalLancet 353(9154): 703-707, 1999.Kritchevsky D: Dietary guidelines: the rationale for intervention. Cancer72(Suppl 3): 1011-1014, 1993.Lee HP, Gourley L, Duffy SW, et al.: Colorectal cancer and diet in an AsianNutrition and Cancer 14(1): 5-13, 1990.Lee HP, Gourley L, Duffy SW, et al.: Colorectal cancer and diet in an Asianpopulation--a case-control study among Singapore Chinese. InternationalJournal of Cancer 43(6): 1007-1016, 1989.Patel NG. Ayurveda: The Traditional Medicine of India.in Folk Medicine:The Art and