A Trial Comparing Intensity Modulated Radiation Therapy (IMRT) With Conventional Radiation Therapy in Stage IIB Carcinoma Cervix

• ClinicalTrials.gov Identifier: NCT00193804
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Last Update Posted: September 16, 2019
• Sponsor: Tata Memorial Hospital
• Collaborator: Varian Medical Systems
• Information provided by (Responsible Party): Sk Shrivastava, Tata Memorial Hospital

Tracking Information

• First Submitted Date: September 13, 2005
• First Posted Date: September 19, 2005
• Last Update Posted Date: September 16, 2019
• Study Start Date: February 2005
• Actual Primary Completion Date: June 20, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 26, 2017): To compare the normal tissue toxicities (Acute & Late) of standard radiation therapy with IMRT [ Time Frame: 2017 ]

Original Primary Outcome Measures (submitted: September 13, 2005)

• 1. To compare the normal tissue toxicities (Acute & Late) of standard radiation therapy with IMRT
• 2. To evaluate the IMRT in Stage IIB carcinoma cervix
• 3. To compare the disease free survivals

Current Secondary Outcome Measures (submitted: March 26, 2017)

• To compare the disease free survivals [ Time Frame: 2017 ]
• To compare the quality of life in both the groups [ Time Frame: 2017 ]
• To compare the overall survivals [ Time Frame: 2017 ]

Original Secondary Outcome Measures (submitted: September 13, 2005)

• 1. To compare the overall survivals
• 2. To compare the quality of life in both the groups

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial Comparing Intensity Modulated Radiation Therapy (IMRT) With Conventional Radiation Therapy in Stage IIB Carcinoma Cervix
• Official Title: A Phase II Randomized Trial Comparing Intensity Modulated Radiation Therapy (IMRT) With Conventional Radiation Therapy in Stage IIB Carcinoma Cervix
• Brief Summary: A study to evaluate the efficacy of Intensity Modulated Radiation Therapy (IMRT) as compared to Standard Conventional Radiotherapy Alone in the treatment of carcinoma cervix. Concomitant Weekly Cisplatin chemotherapy will be given as a routine, which is a standard of care today for early stage cervical cancers including stage IIB. The benefits of using IMRT in reducing radiation-induced toxicity are well known. Since this treatment modality has not yet been validated and studied in a randomized trial setting, the present study is being undertaken. The study arm of IMRT has the potential to reduce the toxicities by 15-20%, but is associated with labor intense procedure requiring many hospital visits before actual start of treatment.

Detailed Description

Carcinoma Cervix is the commonest malignancy seen in Indian women and constitutes approximately 10% of all cancers at Tata Memorial Hospital (1). It is also the leading cause of cancer mortality in India. Nearly 85% of the patients present with advanced stages (FIGO Stage II/III). The main stay of treatment has traditionally been radical radiation therapy with 80-90% of patients requiring radiation in their lifetime and over decades the survival rates have achieved a plateau of 30 - 55% at 5 years.

Radiation therapy is usually a combination of external beam and intracavitary brachytherapy. External beam radiation includes irradiation of primary tumor and nodal areas of risk. Higher Doses of external beam radiation is limited due to normal critical organs namely, small bowel, rectum and bladder. A major concern with pelvic radiation is the considerable volume of both small bowel and rectum is included in the radiation treatment fields. Unsurprisingly, gastrointestinal radiation reactions include diarrhea while late sequelae include small bowel obstruction, enteritis and diarrhea are common (2-4). The benefits of multiple fields, high energy beams, customized blocking and low fraction sizes are well known (4). Various methods have been used to reduce the small bowel complications. Surgical methods include absorbable meshes (5), tissue expanders (6) and omentoplasty (7). However, these approaches are not feasible in patients undergoing definitive radiation. Apart from small bowel toxicity, late rectal and bladder complications are also of a major concern. The clinical manifestations vary from mild proctitis, stricture, bleeding ulcers and fistula formation to hemorrhagic cystitis requiring cystectomy. Grade III radiation cystitis and proctitis reported are in the range of 3-15% with radiation alone.

Moreover, of late the pattern of practice is increasingly being emphasized on concomitant chemo radiation (8,9). The addition of chemotherapy though has no doubt improved the survivals, but has also led to increase in normal tissue toxicities. In the RTOG 90-01 and 92-10 there is alarming increase in the gastro intestinal (35% grade III and grade IV) and genitourinary (9% grade III and grade IV).

The changes in the treatment policies and the toxicities associated with wide pelvic radiation therapy demand for better normal tissue sparing radiation techniques or radioprotective agents. Three Dimensional Conformal Radiation Therapy (3D-CRT) to some extent has successfully achieved some normal tissue sparing. Intensity-modulated radiotherapy (IMRT) is an important recent advance in radiation therapy and is at the forefront of Translational Research. With 3DCRT the radiation intensity is generally uniform within the radiation portal whereas in IMRT the dose intensity within the portal varies with the use of beamlets, thereby allows a higher degree of conformation to the tumor than previously possible and allows concave isodose profiles to be generated.

Over last 10 years, IMRT has been successfully used in the treatment of prostate, head and neck and brain tumors. IMRT in pelvic radiation has the potential to reduce the dose as well as the volume of rectum, bladder and small bowel irradiated significantly and thereby translating into a decrease in the incidence and severity, of acute and late gastro-intestinal and genito-urinary toxicities. Several dosimetric studies have been reported to confirm the role of IMRT in reducing toxicities with pelvic radiation therapy (10,11). These dosimetric studies have reported that the volume of small bowel irradiated to the prescription dose by a factor of 2 compared with conventional radiation. The average volume of bladder and rectum irradiated is also reduced by 23% (12). In our series of 10 patients treated, IMRT in pelvic radiation therapy apart from reducing the hot spot volumes and better conformity index to the target volume, also significantly reduces the volumes of high dose regions in small bowel region (by 17%), rectum (by 50-60%) and bladder (by 40-50%) [unpublished data]. In another series of early report on outcome of 40 patients treated with IMRT to whole pelvis, Arno el al. have demonstrated that there is a significant reduction in acute radiation related toxicities, but it is too early to comment on late sequelae since the follow-up is short and has concluded that, this novel approach definitely needs to be validated in a trial setting. (13)

• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Probability Sample
• Study Population: Patients with histologically proven cervical cancers, FIGO Stage IIb eligible for the study will be invited for the study
• Condition: Cancer of Cervix

Intervention

Radiation: IMRT

IMRT in cervical cancers

Study Groups/Cohorts

2

Patients with histologically proven, cervical cancer FIGO Stage IIB eligible will be invited for the study. The patients will recieve either 3D conformal radiation or IMRT external radiation with concomitant cisplatin chemotherapy followed by brachytherapy.

Intervention: Radiation: IMRT

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 13, 2005): 200
• Original Enrollment: Same as current
• Actual Study Completion Date: June 30, 2019
• Actual Primary Completion Date: June 20, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically proven squamous carcinoma or adenocarcinoma of cervix
• Performance index WHO grade 0 or 1
• Patients below 65 years of age
• FIGO Stage IIB
• Normal ECG and Cardiovascular system
• Normal hematological parameters
• Normal renal and liver function tests

Exclusion Criteria:

• Co-morbid conditions like medical renal disease
• Medical or Psychological condition that would preclude treatment
• H/o Previous treatment / Pregnancy
• Patient unreliable for treatment completion and follow-up.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: India

Administrative Information

• NCT Number: NCT00193804
• Other Study ID Numbers: TMH/158/2004/Cx_IMRT TRIAL
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Sk Shrivastava, Tata Memorial Hospital
• Original Responsible Party: Not Provided
• Current Study Sponsor: Tata Memorial Hospital
• Original Study Sponsor: Same as current
• Collaborators: Varian Medical Systems

Investigators

• Principal Investigator: Shyamkishore J Shrivastava, MD, DNB (RT); Professor & Head, Radiation Oncology, Tata Memorial Hospital

• PRS Account: Tata Memorial Hospital
• Verification Date: September 2019