Cancer of CervixCRACxNCT00193791
Concomitant Chemoradiation in Advanced Stage Carcinoma Cervix
A study testing CT + RT in people with Cancer of Cervix, run by Tata Memorial Hospital at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Cancer of Cervix
- What is being tested?
- CT + RT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 850 participants
- Where
- 1 siteIndia
- Study dates
- 7 Jul 2003to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Concomitant Chemo-radiation in Advanced Stage Carcinoma Cervix: A Phase III Randomized Trial
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.
Read the 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.
- Conditions
- Cancer of Cervix
- Being tested
- CT + RT
- Keywords
- Carcinoma Cervix, FIGO Stage IIIB, Radiation therapy, Chemoradiation, Treatment related toxicities, Cervical Cancer, Cervix Cancer
- Medical subject headings
- Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CT + RTOther
Injection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Radiation (RT) Alone | No intervention | Standard radical radiation therapy alone |
| CT + RT | Experimental | Injection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy Receives: Other: CT + RT |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the disease free survivals.
Measured: December 2009
Secondary outcomes (4)
To compare the overall survivals
Measured: December 2010
To compare the distant metastasis rates
Measured: December 2010
To compare the quality of life in both the groups
Measured: December 2010
To compare the normal tissue toxicities (Acute & Late) of standard radiation therapy with concomitant chemo-radiation.
Measured: June 2017
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Sep 2005 (estimated)
- Study start7 Jul 2003
- Primary completionMay 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cancer of CervixStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Concomitant chemo-radiation versus radiation alone
- Masking
- None (open label)
- Enrolment
- 850 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tata Memorial Hospital
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Sk Shrivastava, Tata Memorial Hospital
- Investigators
- Shyamkishore J Shrivastava, MD,DNB(RT), Principal investigator, Professor & Head, Department of Radiation Oncology, Tata Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00193791
- Sponsor's protocol ID
- TMH/114/2003/CRACX TRIAL
- Acronym
- CRACx
- Status last verified
- Sep 2019
- First submitted
- 13 Sep 2005
- Last updated
- 17 Sep 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Individual patient data (IPD) related to patient characteristics, treatment and outcome variables.
Publications
Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6. doi: 10.1016/S0140-6736(01)05965-7.
PubMed 11564482Lukka H, Hirte H, Fyles A, Thomas G, Elit L, Johnston M, Fung MF, Browman G; Cancer Care Ontario Practice Guidelines Initiative Gynecology Disease Site Group. Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis. Clin Oncol (R Coll Radiol). 2002 Jun;14(3):203-12. doi: 10.1053/clon.2002.0076.
PubMed 12109823Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, Kerkar RA, Maheshwari A, Shylasree TS, Ghosh J, Bajpai J, Gurram L, Gulia S, Gupta S; Gynecologic Disease Management Group. Cisplatin Chemoradiotherapy vs Radiotherapy in FIGO Stage IIIB Squamous Cell Carcinoma of the Uterine Cervix: A Randomized Clinical Trial. JAMA Oncol. 2018 Apr 1;4(4):506-513. doi: 10.1001/jamaoncol.2017.5179.
PubMed 29423520
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Concomitant Chemo-radiation in Advanced Stage Carcinoma Cervix: A Phase III Randomized Trial
- ClinicalTrials.gov ID
- NCT00193791
- Acronym / sponsor ID
- CRACx / TMH/114/2003/CRACX TRIAL
- Conditions
- Cancer of Cervix
- Keywords
- Carcinoma Cervix, FIGO Stage IIIB, Radiation therapy, Chemoradiation, Treatment related toxicities, Cervical Cancer, Cervix Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 850 participants (actual)
- Lead sponsor
- Tata Memorial HospitalOther government
- Study start
- 7 Jul 2003 (actual)
- Primary completion
- May 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 19 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Concomitant chemo-radiation versus radiation alone
| Arm | Type | Receives |
|---|---|---|
| Radiation (RT) Alone | No intervention | –Standard radical radiation therapy alone |
| CT + RT | Experimental | Other: CT + RTInjection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CT + RTInjection Cisplatin 40mg/m2 weekly for 5 weeks during the entire course of external radiation therapy | Other | CT + RT |
Primary outcome
To compare the disease free survivals.
Time frame: December 2009
4 secondary outcomes
To compare the overall survivals
Time frame: December 2010
To compare the distant metastasis rates
Time frame: December 2010
To compare the quality of life in both the groups
Time frame: December 2010
To compare the normal tissue toxicities (Acute & Late) of standard radiation therapy with concomitant chemo-radiation.
Time frame: June 2017
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2019.
- Background: PubMed 11564482Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001 Sep 8;358(9284):781-6. doi: 10.1016/S0140-6736(01)05965-7.
- Background: PubMed 12109823Lukka H, Hirte H, Fyles A, Thomas G, Elit L, Johnston M, Fung MF, Browman G; Cancer Care Ontario Practice Guidelines Initiative Gynecology Disease Site Group. Concurrent cisplatin-based chemotherapy plus radiotherapy for cervical cancer--a meta-analysis. Clin Oncol (R Coll Radiol). 2002 Jun;14(3):203-12. doi: 10.1053/clon.2002.0076.
- Derived from this study: PubMed 29423520Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, Kerkar RA, Maheshwari A, Shylasree TS, Ghosh J, Bajpai J, Gurram L, Gulia S, Gupta S; Gynecologic Disease Management Group. Cisplatin Chemoradiotherapy vs Radiotherapy in FIGO Stage IIIB Squamous Cell Carcinoma of the Uterine Cervix: A Randomized Clinical Trial. JAMA Oncol. 2018 Apr 1;4(4):506-513. doi: 10.1001/jamaoncol.2017.5179.
- Individual participant dataSharing planned: Yes. Individual patient data (IPD) related to patient characteristics, treatment and outcome variables.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shyamkishore J Shrivastava, MD,DNB(RT) principal investigator
Professor & Head, Department of Radiation Oncology, Tata Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CT + RT in people with Cancer of Cervix, run by Tata Memorial Hospital at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the disease free survivals. (time frame: December 2009). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00193791, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2019.