Concomitant Chemoradiation in Advanced Stage Carcinoma Cervix (CRACx)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2008 by Tata Memorial Hospital.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Tata Memorial Hospital
ClinicalTrials.gov Identifier:
NCT00193791
First received: September 13, 2005
Last updated: July 20, 2011
Last verified: July 2008
  Purpose

A study to evaluate the efficacy of concomitant chemoradiation as compared to radiotherapy alone. Concomitant chemoradiation is not a new treatment modality for carcinoma cervix. Studies have shown improvement in survivals with chemoradiation, but majority of the patients was in early stages. Since this treatment modality has not been tested adequately in advanced stages in our setting, the present study is being undertaken. The study arm of chemoradiation has the potential to improve the survivals by 10%, but is associated with additional 5% risk of toxicities, which are treatable. In the study arm, apart form the standard radiotherapy treatment, you will receive weekly chemotherapy injections (Cisplatin) during external radiation therapy. The study arm is associated with additional 5% acute hematological and gastrointestinal toxicities, which are treatable with medications, blood transfusions, modifications in the ongoing treatment etc.


Condition Phase
Cancer of Cervix
Phase 3

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Concomitant Chemo-radiation in Advanced Stage Carcinoma Cervix: A Phase III Randomized Trial

Resource links provided by NLM:


Further study details as provided by Tata Memorial Hospital:

Primary Outcome Measures:
  • To evaluate the single agent concomitant chemotherapy (Cisplatin) in Stage IIIB carcinoma cervix [ Time Frame: December 2008 ] [ Designated as safety issue: No ]
  • To compare the disease free survivals. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]
  • To compare the normal tissue toxicities (Acute & Late) of standard radiation therapy with concomitant chemo-radiation. [ Time Frame: December 2009 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To compare the overall survivals [ Time Frame: December 2010 ] [ Designated as safety issue: No ]
  • To compare the distant metastasis rates [ Time Frame: December 2010 ] [ Designated as safety issue: No ]
  • To compare the quality of life in both the groups [ Time Frame: December 2010 ] [ Designated as safety issue: No ]

Estimated Enrollment: 850
Study Start Date: October 2003
Estimated Study Completion Date: December 2011
Groups/Cohorts
1
Standard radical radiation therapy alone
2
Injection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy

Detailed Description:

Carcinoma cervix is the commonest malignancy seen in Asian women and constitutes approximately 30% of all cancers (1). It is also the leading cause of cancer mortality in India. Nearly 50% of the patients present with advanced stages (FIGO Stage III/IV). The main stay of treatment has traditionally been radical radiation therapy and over decades the survival rates have achieved a plateau of 30 - 45% at 5 years. In developing countries the socioeconomic problems, illiteracy, late presentation and irregular follow-up have further compromised our survivals. Over the last decade there have been studies on the use of chemo-radiotherapy in carcinoma cervix. Over 19 randomized trials have been published addressing the issue of chemo-radiotherapy. However, heterogeneous data, poor randomization, inadequate number of patients, sub-optimal radiotherapy, non-uniform use of chemotherapeutic drugs, its sequencing and poor documentation have not yet provided the evidence to substantially alter the practice. Hence, meta-analysis of these trials was undertaken to further evaluate the role of chemo-radiotherapy in carcinoma cervix (2,3).

The first meta-analysis published by Cochrane Collaborative Group of 4580 randomized patients (19 randomized trials) suggested that chemo-radiation did show an absolute survival benefit improvement both in progression free and overall survivals by 16% and 12% respectively (p<0.0001). The survivals were significantly better with Cisplatin based concomitant chemo-radiation (p<0.0001). Incidentally, the distant metastasis rates were also significantly lower in chemo-radiation (p<0.0001). However, all these benefits were seen only in early stages. In addition, acute grade 3/4 hematological and gastro-intestinal toxicities were higher with chemo-radiation (additional 8% and 5% respectively). The data was insufficient to report on late toxicity (2).

The second meta-analysis of 9 randomized trials, recently published by the Canadian Group to evaluate only cisplatin based concomitant chemo-radiation confirms the improvement in overall survival (4year survival data) in advanced stages, bulky IB tumors (prior to surgery) and high risk early disease (post-surgery). Although acute grade 3/4 hematological and gastro-intestinal toxicities were higher in chemo-radiation, they were short-lived, with only 2 deaths and the remaining resolved with medical treatment. There was no significant increase in the late toxicity from the data available.

Both the Cochrane and Canadian meta-analysis have to a large extent tried to address the role of concomitant chemo-radiation, but Carcinoma Cervix Stage III accounted for only 30-35% and moreover evaluation with optimal radiation schedules and comparison of late toxicities still remains unanswered. What is more important is that the cisplatin is relatively inexpensive and is available worldwide. This means that cisplatin-based chemo-radiation is affordable in the developing countries where carcinoma cervix still forms the major cancer. However, the role of chemo-radiation in Carcinoma Cervix Stage IIIB in a developing countries including India still remains unexplored. We propose this randomized study to evaluate the role and benefit of chemo-radiation in-patients with cervical cancer.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with histologically proven (SQ CA) cervical cancer FIGO Stage IIIB suitable for the study will be invited for the study

Criteria

Inclusion Criteria:

  • Histologically proven squamous carcinoma of cervix
  • Performance index WHO grade 0 or 1
  • Patients below 65 years of age
  • FIGO Stage IIIB
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00193791

Contacts
Contact: Shyamkishore J Shrivastava, MD,DNB(RT) +91-22-2417 7163 sshyam@mtnl.net.in
Contact: Umesh M Mahantshetty, DMRT,MD,DNB +91-22-2417 7168 drumeshm@yahoo.com

Locations
India
Tata Memorial Hospital Recruiting
Mumbai, Maharastra, India, 400 012
Contact: Shyamkishore J Shrivastava, MD, DNB    +91-22-2417 7163    sshyam@mtnl.net.in   
Contact: Umesh M Mahantshetty, MD,DNB (RT)    +91-22-2417 7168    drumeshm@yahoo.com   
Principal Investigator: Shyamkishore J Shrivastava, MD, DNB (RT)         
Sponsors and Collaborators
Tata Memorial Hospital
Investigators
Principal Investigator: Shyamkishore J Shrivastava, MD,DNB(RT) Professor & Head, Department of Radiation Oncology, Tata Memorial Hospital
  More Information

No publications provided

Responsible Party: Dr Sk Shrivatsava, Tata Memorial Hospital
ClinicalTrials.gov Identifier: NCT00193791     History of Changes
Other Study ID Numbers: TMH/114/2003/CRACX TRIAL
Study First Received: September 13, 2005
Last Updated: July 20, 2011
Health Authority: India: Department of Atomic Energy

Keywords provided by Tata Memorial Hospital:
Carcinoma Cervix
FIGO Stage IIIB
Radiation therapy
Chemoradiation
Treatment related toxicities
Cervical Cancer
Cervix Cancer

Additional relevant MeSH terms:
Carcinoma
Uterine Cervical Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female

ClinicalTrials.gov processed this record on September 30, 2014