Docstoc

TITLE_ Phase III Randomized Study of Jatyadi Oil

Document Sample
TITLE_ Phase III Randomized Study of Jatyadi Oil Powered By Docstoc
					                 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:
• 1999 - 8.9 million American had cancer.
• NCRP: 7- 8 lacks new cancer pt. Per year
  in India.
• 30- 35000 new cancer pt. Diagnose in
  Gujarat.
• 3500 Apr. Pt. Visit at RCS.
        Causes            of cancer:
•   Physical factor.
•   Chemical factor.
•   Viral factor.
•   Genetic factor.
•   Industrial factor.
•   Ionizing radiation.
•   Life style factor.
    OTHER RISK FECTORS:
• CELL PHONE.
• TOBBACO IN ANY FORM.
• DIETARY FAT.
• LESS CONSUPTION OF VEG. AND
  FRUITS.
• LESS EXERCISE.
• HEAVY WEIGHT.
     SEVEN SIGNALS OF
       CANCER.
• ANY SORE THAT DOES NOT HEAL.
• BLEEDING FROM ANY SITE OF THE
  BODY.
• CHANGES IN WARTS / BIRTH MARKS.
• CHANGES IN HABIT OF STOOL AND
  URINE.
• CHANGE OF VOICE AND
  CONTINEIOUS COUGH.
• DIFFICULTY IN SWALLOWING.
Cancer treatment in Ayurveda

• PROPHYLACTIC
• PALLIATIVE
• SUPPORTIVE
• CURATIVE
Thanks. ………   a
   lot…….
Researcher:
Dr. Bhavna G. Joshi(Kansara)
M.D. Ayurveda Oncology

Dr. Gaurang Joshi
B.A.M.S. Immunology.



              Atharva Ayurveda Hospital
              and cancer research center.
                   Rajkot. Gujarat.
                           OBJECTIVES

                                 Primary
Determine 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.

                            Secondary
  Compare 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 Rationale

The 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 part
                10 Katurohini (Rz.)           Picrorhiza kurroa                               1 part
                11 Manjishtha (Rz.)           Rubia cordifola                                 1 part
                        12 Padmaka (Ht. Wd.)         Prunus cerasoides              1 part
                13 Lodhra (St.Bk.)            Symplocos racemosa                              1 part
                14 Abhaya (Ft. P.)            Terminalia chebula                              1 part
                        15 Nilotpala (Fl.)            Nymphaea stellata             1 part
                        16 Tutthaka                  Copper sulphate                1 part
                17 Sariva (Rt.)               Hemidesmus indicus                            1 part
                        18 Naktamala bija (Sd.)       Pongamia pinnata              1 part
                     19 Kumari                     Aloe Barbadensis                    1 part
          20 Punarnava                       Boerhaavia Diffusa                                          1 part
                21 Nagkeshar                  Mesua Ferrea                                  1 part
                22 Haritaki                        Terminalia Chebula                       1 part
23 Aswagandha                                  Withenia Somnifera                       1 part

                  24 Taila                      Sesamum indicum seeds                         72 parts
                 25 Water                                                                    288 parts
ENTRY CRITERIA

Disease Characteristics:
Histologically confirmed primary Anal or Rectal Cancer, cervical cancer or any pelvic
tumor.

Must be scheduled to receive radiotherapy

Prior/Concurrent Therapy:

Biologic therapy
Not specified

Endocrine therapy
Not Specified

No prior pelvic radiotherapy .
No prior intensity-modulated radiotherapy
No brachytherapy prior to or after completion of all external beam radiotherapy
Surgery
No prior abdominal-perineal resection or other surgical procedure leaving
the patient without a functioning rectum
No colostomy

Other
More 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 medication

Age   18 and over

Performance status
Not specified

Life expectancy
Not specified

Hematopoietic
Not specified
Renal
Not specified

Gastrointestinal
No 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 stool

Other
Not 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
                  PROJECTED ACCRUAL
A total of 30 patients (15 per treatment arm) will be accrued
               for this study within 3 months.
Study Design Overview

Present 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 any allopathic 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 Schedules

Patients 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 Parameters

Primary:      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 Parameters


Qualitative 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 Studies


A 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 Criteria
The 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 Proceedures

Patients 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 Evaluations


The 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 assessment will 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/Response
Duration

At 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 Grade

report 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 Analysis

Quality 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 Matters

To comply with Good Clinical Practice, important
administrative obligations relating to investigator
responsibilities, monitoring, archiving data, audits,
confidentiality and publications must be fulfilled.
APPENDIX B
NCIC CTG EXPANDED COMMON TOXICTTY CRITERIA
* Denotes NCTC CTG specific criteria. Any toxicity which causes death should be given grade 5
GRADE              o     1            1                  2                3                  4
                   ALLERGY
ALLER Allergy none                    transient rash, fever <38°c, 100.4T Urticaria, fever^38°c, 100.4°F, mild bronchospasm serum sickness,
bronchospasm, req parenteral meds anaphylaxis
                   Fever 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                     j                Mild             Moderate           severe            life thp*?^»»njKg
                   BLOOD/BONE MARROW (SI UNITS)
BL WBC White Blood Count (WBC)                           24.0        10*/L3.0-3.9            2.0-2.9           1.0-1.9           <1.0
BLPLT Platelets WNL              VflL                    75-0-normal      50.0-74.9          25.0-49.9         <25.0
BLHGB Hemoglobin (Hgb)                WNL           g/L 100-nonnal        80-99              65-79             <65
BLGRA
Grannlocytes (i.e nents + bands) 22.0              \<PlL 1.5-1.9          1.0-1.4            05-0.9            <0.5
BLLYM Lymphocytes                     22.0          10/L 1.5-1.9          1.0-1.4            05-0.9            <0.5
BLHEM Hemorrhage resulting from thrombocytopenia [clinical)               none               mild, do transfusion (includes bruiseyheinatoma,
petechiae)         gross, 1-2 units transfusion per episode               gross, 3-4 units transfusion per episode               massive, >4 units
transfusion per episode
BL OTH other* none                    Mild               moderate         severe             life threatening
                                      CANCER RELATED SYMPTOMS
CA DEA Death from malignant
Disease within 30 days of treatment * (grade =5)




CAPAI Cancer pain*                  none              pain, but no treatment leq           pain controlled with non-opioids pain controlled with
opioids           uncontrollable pain
CA SEC Second malignancy *          none              —                                                       present            —
CAOTH*            none              Mild              moderate           severe            life threatening
CARDIOVASCULAR
CD ART Arterial* (non my ocar dial)                   none               "                 *                  transient events (eg. transient ischemia
attack)           permanent event (eg. cerebral vascular accident)
CD VEN Venous*                      none              Superficial (excludes IV site reaction -code SK LTD) deep vein thrombosis not req
anticoagulant therapy               deep vein thrombosis req anticoagulant therapy         pulmonary embolism
CDDYS Dysrhythmias                  none              Asymptomatic, transient, req no therapy                 recurrent or persistent, req no therapy
                  req therapy       req monitoring, or hypotension, or ventricular tachycardia, or fibrillation
References:

Alberts DS, Martinez ME, et al, and the Phoenix Colon Cancer Prevention
Physicians' Network: Lack of effect of a high-fiber cereal supplement on the
recurrence of colorectal adenomas. New England Journal of Medicine 342(16):
1156-1162, 2000.
Augustsson K, Skog K, Jagerstad M, et al.: Dietary heterocyclic amines and
heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population stu
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 on
the 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 on
in Cancer. New York: Marcel Dekker, 1992, pp 55-84.
Kampman E, Giovannucci E, van't Veer P, et al.: Calcium, vitamin D,
dairy
foods, and the occurrence of colorectal adenomas among men and women
in two
prospective studies. American Journal of Epidemiology 139(1): 16-29,
1994.
Kritchevsky D: Dietary guidelines: the rationale for intervention. Cancer
Lack of effect of a low-fat, high-fiber diet on the recurrence of colorectal
Lancet 353(9154): 703-707, 1999.
Kritchevsky D: Dietary guidelines: the rationale for intervention. Cancer
72(Suppl 3): 1011-1014, 1993.
Lee HP, Gourley L, Duffy SW, et al.: Colorectal cancer and diet in an
Asian
Nutrition and Cancer 14(1): 5-13, 1990.
Lee HP, Gourley L, Duffy SW, et al.: Colorectal cancer and diet in an
Asian
population--a case-control study among Singapore Chinese. International
Journal of Cancer 43(6): 1007-1016, 1989.
Patel NG. Ayurveda: The Traditional Medicine of India.in Folk
Medicine:The Art and

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:2
posted:3/27/2014
language:English
pages:34