Radiotherapy + Metronidazole vs Radiotherapy Alone In Improving Treatment Outcomes in Advanced Cervical Cancer in Uganda
Information source: Makerere University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cervix Carcinoma
Intervention: Radiotherapy plus metronidazole (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: Makerere University Official(s) and/or principal investigator(s): Peter Kibuuka, MBChB, Principal Investigator, Affiliation: Makerere University Mike Kagawa, MMed, Study Director, Affiliation: Makerere University Anthony Okoth, MMed, Study Director, Affiliation: Mulago National Referral Hospital Joseph Kigula-Mugambe, MMed, Study Director, Affiliation: Mulago National Referral Hospital
Summary
The objective of the study was to determine whether there was a difference in the
effectiveness of Radiotherapy alone compared with Radiotherapy plus Metronidazole in the
treatment of women with advanced cancer of the cervix in Mulago hospital. It was a
randomized controlled trial composed of 38 women altogether, with one group composed of
randomly selected women with advanced cancer of the cervix treated with radiotherapy alone
and the other group composed of similar women but treated with radiotherapy and
metronidazole.
Clinical Details
Official title: A Randomized Clinical Trial of Radiotherapy and Metronidazole Versus Radiotherapy Alone in Anaemic Patients With Advanced Cervical Cancer In Mulago
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Caregiver, Investigator), Primary Purpose: Treatment
Primary outcome: Percentage reduction in tumor volume as compared to baseline
Secondary outcome: To determine the safety of metronidazole and radiotherapy as measured by number of complications in both arms
Detailed description:
Methods A double blinded placebo controlled trial was used to determine the efficacy and
safety of metronidazole as an adjunct to radiotherapy compared to radiotherapy alone for the
treatment of anemic patients with advanced cancer of the cervix as measured by clinical
response.
The unit of randomization was a woman with cancer of the cervix from stage IIIB to IVB and
hemoglobin level of 12g/dl or less. The ones who consented to the study were enrolled and
randomized to either the radiotherapy and metronidazole (RT+MX) or the radiotherapy and
placebo (RT) arms.
The study was conducted in both the Department of Radiotherapy and the Department of
Obstetrics and Gynecology of Mulago hospital, Kampala, Uganda.
Women eligible for inclusion in the study were those with cancer of the cervix who had
histologically proven stage IIB to IVB, fit for radiotherapy and an Hb of 12g/dl or less.
Women taking metronidazole treatment for other reasons other than
radio-sensitization and those with a history of neuropathy or with hypersensitivity to
metronidazole were excluded.
A randomization code was generated by an independent statistician who did not participate in
the study nor visit the study site. The randomization code was then placed in an opaque and
sealed envelope and sent a copy to the pharmacist in the study centre so that he got to know
what to put in each envelope for study participants. The envelopes were kept by the study
pharmacist who dispensed the drugs. The code was to be broken when the principal
investigator felt that the blinded treatment was harmful to the patient, either because of
the side effects or failure to respond in which case he would urgently notify the data
safety and review board with the view of breaking the code for that particular patient.
The total number of study participants was 40. In view of the need for equal numbers at
equally spaced points in the sequence of the study, random permuted blocks of four patients
each were used. Letter A was used for Radiotherapy & Metronidazole (RT+MX) and B for
Radiotherapy alone (RT) assignment. The blocks were as follows:
AABB - block number 1 ABBA- block number 2 BBAA - block number 3 ABAB - block number 4 BAAB
- block number 5 BABA - block number 6 Treatment modalities included radiotherapy
administration plus Metronidazole or paracetamol administration. Radiotherapy administration
was in two phases using tele-therapy and brachy-therapy. The first phase was tele-therapy
via parallel-opposed portals (half the dose in antero-posterior and the other half in the
postero-anterior direction) from Co-60 radiation source, with a total dose of 50 Gy given in
25 fractions of 2 Gy/day (Monday to Friday and weekend rest) for five weeks. The patients
were then given a break of 1-4 weeks before getting the second phase of treatment. The
second phase was brachy-therapy from a Cs-137 source, whereby a single dose of 30Gy was
delivered at point A at a rate of 2. 55 Gy/ hour for 7 hours and 50 minutes, via a uterine
Tandem and two vaginal Ovoids. In case of severe vaginal stenosis during the first phase, a
cylindrical applicator would be used.
Participants in the study arm received 1gm (two suppositories) of metronidazole per rectum
30 minutes before radiotherapy for every other radiotherapy session and it was omitted in
the two rest days of Saturday and Sunday. Participants in the control arm received 500mg
(two suppositories) of paracetamol as a placebo on similar days. The study was conducted
during day time.
The metronidazole and paracetamol suppositories looked identical in colour, smell and shape.
Although the packaging was similar it had different labels. They were therefore dispensed
when ready to use and out of the packaging and each patient got two suppositories in a
session.
Subjective assessment of the clinical symptom response among study patients was done every
day on the Mulago radiotherapy department grading system for cancer response (Kigula-Mugambe
2001). Response was graded into 4 grades as follows; Grade 1: Complete response (no tumour
clinically seen and all the symptoms and signs have subsided) Grade 2: Partial response
(at least 50% of the symptoms and signs have subsided) Grade 3: No response (symptoms and
signs have not changed with treatment) Grade 4: Disease progression with treatment
(symptoms and signs at the end of treatment worse than the beginning of treatment)
Measurement of tumour regression was done by a trans-abdominal real time B-mode ultrasound
scan which was both at the beginning and the end of tele-therapy. It was aimed at measuring
the widest transverse diameter, the thickness and length of the cervical tumour. The tumour
volume was then computed by the ultrasound machine. Patients needed to have a full urinary
bladder before ultrasound was done. Local tumour response was measured using the formula
below Local tumour response = {(Volume A - Volume B)/Volume A} X 100% Where A was the tumour
volume at the beginning of treatment and B was the tumour volume after the course of
teletherapy.
Complications were subjectively assessed using the Franco-Italian (Fl) glossary for
radiotherapy complications of March 1990 as follows:
Grade 0: No complication. Grade 1: Mild complications (minor symptoms/signs not requiring
treatment or requiring simple outpatient treatment) Grade 2; Moderate complications (these
require hospitalization but without a treatment break).
Grade 3: Severe complication (distressing complications which lead to a treatment break and
or life threatening morbidity e. g. fistula formation) Grade 4: Complications leading to
death/fatal
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
Criteria:
Inclusion Criteria:
- Women with cancer of the cervix who had histologically proven stage IIB to IVB
cancer of the cervix.
- Women with cancer of the cervix who had been assessed and found fit for radiotherapy
- Women with cancer of the cervix who had Hb 12g/dl and below.
Exclusion Criteria:
- Women who were already on metronidazole treatment for other reasons
other than radio sensitization
- Women who had a history of neuropathy
Locations and Contacts
Additional Information
Starting date: June 2009
Last updated: September 4, 2013
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