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Concomitant Chemoradiation in Advanced Stage Carcinoma Cervix (CRACx)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00193791
Recruitment Status : Completed
First Posted : September 19, 2005
Last Update Posted : September 17, 2019
Information provided by (Responsible Party):
Sk Shrivastava, Tata Memorial Hospital

Brief Summary:
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 or disease Intervention/treatment Phase
Cancer of Cervix Other: CT + RT Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 850 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Concomitant chemo-radiation versus radiation alone
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Concomitant Chemo-radiation in Advanced Stage Carcinoma Cervix: A Phase III Randomized Trial
Actual Study Start Date : July 7, 2003
Actual Primary Completion Date : May 2017
Actual Study Completion Date : December 2017

Arm Intervention/treatment
No Intervention: Radiation (RT) Alone
Standard radical radiation therapy alone
Experimental: CT + RT
Injection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy
Other: CT + RT
Injection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy

Primary Outcome Measures :
  1. To compare the disease free survivals. [ Time Frame: December 2009 ]

Secondary Outcome Measures :
  1. To compare the overall survivals [ Time Frame: December 2010 ]
  2. To compare the distant metastasis rates [ Time Frame: December 2010 ]
  3. To compare the quality of life in both the groups [ Time Frame: December 2010 ]
  4. To compare the normal tissue toxicities (Acute & Late) of standard radiation therapy with concomitant chemo-radiation. [ Time Frame: June 2017 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologically proven squamous carcinoma of cervix
  • Performance index world health organization (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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00193791

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Tata Memorial Hospital
Mumbai, Maharastra, India, 400 012
Sponsors and Collaborators
Tata Memorial Hospital
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Principal Investigator: Shyamkishore J Shrivastava, MD,DNB(RT) Professor & Head, Department of Radiation Oncology, Tata Memorial Hospital
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Sk Shrivastava, Professor and Head, Radiation Oncology, Tata Memorial Hospital Identifier: NCT00193791    
Other Study ID Numbers: TMH/114/2003/CRACX TRIAL
First Posted: September 19, 2005    Key Record Dates
Last Update Posted: September 17, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual patient data (IPD) related to patient characteristics, treatment and outcome variables.
Keywords provided by Sk Shrivastava, Tata Memorial Hospital:
Carcinoma Cervix
Radiation therapy
Treatment related toxicities
Cervical Cancer
Cervix Cancer
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases