Cervical CancerPhase 2NCT01276730
Advanced Cervical Cancer Trial in India
A Phase 2 study testing Interferon, Retinoic Acid and radiation and Cisplatin and radiation in people with Cervical Cancer, run by University of Louisville at 1 site in India.
Trial summary
The study objective: To evaluate the response and survival rates after treating stage III cervical cancer with retinoic acid and interferon-α combined with radiotherapy in the study group. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Cervical Cancer
- What is being tested?
- Interferon, Retinoic Acid and radiation and Cisplatin and radiation
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 209 participants
- Where
- 1 siteIndia
- Study dates
- Oct 2007to Aug 2015
- Phase
- Phase 2
- 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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Advanced cervical cancer
Who cannot join
- Previously treated for cancer of the cervix
- Karnofsky Performance Score less than 50
- Renal dysfunction ( Serum creatinine > 2.0mg/dl)
- Hepatic dysfunction (Serum bilirubin> 2.0 mg/dl, transaminases > 1.5 times normal)
- Pregnant or lactating women: Women will be tested by pregnancy test for possibility of existing pregnancy. Those that meet criteria of trial will be asked to promise that they don't become pregnant; barrier contraception will be recommended.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Phase II Two-Arm, Randomized Clinical Trial of Concomitant Immunotherapy (With Interferon-Alpha and Retinoic Acid) and Radiation Therapy for the Treatment of Advanced Cervical Cancer in India
The study objective:
- To evaluate the response and survival rates after treating stage III cervical cancer with retinoic acid and interferon-α combined with radiotherapy in the study group.
- To evaluate the response and survival rates after treating stage III cervical cancer patients with concomitant cisplatin and radiotherapy in the control group.
- To evaluate the safety and tolerability of the combination of retinoic acid, interferon-α and radiation therapy compared with concomitant chemo-radiation therapy.
- To determine if there is an immune response to Human Papillomavirus (HPV) by estimating serum IgG1 and IgG2 antibodies against E7 proteins of HPV types 16 and 18 before and after treatment.
Read more
The study hypothesis:
- The response rates and survival rates of retinoic acid and interferon-α combination with radiation will be better than chemo-radiation to treat stage III cervical cancer.
- Treatment with the retinoic acid, interferon-α and radiation combination therapy will be less toxic and better tolerated than chemo-radiation therapy.
Read the detailed description
A total of 200 women with confirmed diagnosis of invasive cervical cancer, stage III, will be recruited into the study. The patients will be recruited from the Gynecologic Oncology Department of the Chittaranjan National Cancer Institute that registers more than 600 cases of cancer of the cervix per year. Computer-generated numbers will randomize patients into the two treatment arms.
This trial is designed to treat stage III cervical cancer patients with concomitant immunotherapy (with cis-retinoic acid and interferon-α) and radiotherapy in the study arm.
Cancer of the uterine cervix is the second most common cancer among women worldwide and is the cause of the largest number of cancer-related deaths among women in the developing countries. In India, cervical cancer is the commonest cancer among women (126,000 new cases, 71,000 deaths in 2000), accounting for more than a quarter of the global burden of cervical cancer (471,000 new cases and 233,000 deaths).1,2 In contrast, in the U.S., although, there were only 12,200 new cases of cervical cancer and 4,100 deaths in 2003, the United States spends $5 billion per year screening and treating cervical cancer and precancerous lesions.
Advanced cervical cancer is relatively rare in the developed world because of routine PAP testing. However, in a developing country like India, because of the absence of any population based cervical cancer screening programs (HPV testing, PAP smears), nearly 80% of the patients are initially detected at stage III or higher. Cisplatin-based chemotherapy administered along with surgery and radiation is the recommended treatment for advanced cervical cancer in the US and other developed countries.
- Conditions
- Cervical Cancer
- Being tested
- Interferon, Retinoic Acid and radiation, Cisplatin and radiation
- Keywords
- Advanced cervical cancer, India
- 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.
Interferon, Retinoic Acid and radiationDrug
Interferon-α2b will be administered 3 times a week for four weeks at a dose of 3 x 106 IU subcutaneously concomitant with radiotherapy. The first dose will be administered on the day the subject starts radiotherapy; 13-cis-retinoic acid will be administered orally at a dose of 40 mg/day for 1 month starting from day 1 of radiotherapy; a total of 40 to 45 Gy whole pelvis irradiation will be delivered in conventional fractions to both the study group and the control group. Additional parametrial dosages will be delivered to complete 55 Gy. This will be followed by two intracavitary applications of approximately 40-50 Gy, depending on the volume.
Cisplatin and radiationDrug
Weekly cisplatin will be administered concurrent with external beam radiation at a dose of 40mg/m2/week for 5 weeks; a total of 40 to 45 Gy whole pelvis irradiation will be delivered in conventional fractions. Additional parametrial dosages will be delivered to complete 55 Gy. This will be followed by two intracavitary applications of approximately 40-50 Gy, depending on the volume.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | Treatment consists of Interferon, given as a sub-cutaneous injection, 3 times per week for 4 weeks, 20 mg Retinoic Acid tablets, 2 times a day for 30 days. starting from the first day of radiation. Receives: Drug: Interferon, Retinoic Acid and radiation |
| Group B | Active comparator | Treatment consists of radiation and chemotherapy using Cisplatin. Cisplatin, given intravenously, will be administered on the first day of each week, mixed with saline solution, before and after the Cisplatin infusion.
Radiation will be given for a few minutes daily, five days a week, for approximately 5 weeks.
Two weeks after completion of external radiotherapy, subject will receive internal radiation (brachytherapy) once a week for two weeks. For this internal radiation a specially designed instrument will be inserted into the vagina that will be connected to a machine for a few minutes. Receives: Drug: Cisplatin and radiation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Overall survival curves will be computed using the method of Kaplan and Meyer. The difference in survival between the two groups will be compared by log rank test with the O'Brien-Fleming boundaries to control for alpha spending at a planned interim analysis (50% of the total accrual).
Measured: 3 years or death
Secondary outcomes (3)
Response rate
Response rate will be compared between the arms. Response will be determined by radiological imaging and defined to include Complete Response, the disappearance of all gross evidence of disease, and Partial Response, more than 50% reduction in the two largest dimensions of the measurable tumor.
Measured: 3 years or death
Overall toxicity
Fisher's exact test will be used to compare the incidences of WHO toxicities and response rates between the treatment groups.
Measured: 3 years or death
Determine immune response to Human Papillomavirus HPV
By estimating serum IgGl and IgG2 antibodies against E7 protein of HPV types 16 and 18 before and after treatment.
Measured: 3 years to death
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startOct 2007
- Primary completionAug 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cervical CancerStudies of the same condition, open and under way.
- More trials run by University of LouisvilleThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Louisville
- Sponsor type
- University, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Responsible party
- Sponsor
- Investigators
- Partha S Basu, MD, Principal investigator, Chittaranjan National Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276730
- Sponsor's protocol ID
- 464.05
- Status last verified
- Dec 2017
- First submitted
- 2 Nov 2010
- Last updated
- 29 Dec 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Basu P, Jenson AB, Majhi T, Choudhury P, Mandal R, Banerjee D, Biswas J, Pan J, Rai SN, Ghim SJ, Miller D. Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma. Int J Radiat Oncol Biol Phys. 2016 Jan 1;94(1):102-110. doi: 10.1016/j.ijrobp.2015.09.040.
PubMed 26700705
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Phase II Two-Arm, Randomized Clinical Trial of Concomitant Immunotherapy (With Interferon-Alpha and Retinoic Acid) and Radiation Therapy for the Treatment of Advanced Cervical Cancer in India
- ClinicalTrials.gov ID
- NCT01276730
- Acronym / sponsor ID
- 464.05
- Conditions
- Cervical Cancer
- Keywords
- Advanced cervical cancer, India
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- University of LouisvilleUniversity, hospital or other
- Collaborators
- James Graham Brown Cancer Center
- Study start
- Oct 2007
- Primary completion
- Aug 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 13 Jan 2011 (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.
The study objective:
- To evaluate the response and survival rates after treating stage III cervical cancer with retinoic acid and interferon-α combined with radiotherapy in the study group.
- To evaluate the response and survival rates after treating stage III cervical cancer patients with concomitant cisplatin and radiotherapy in the control group.
- To evaluate the safety and tolerability of the combination of retinoic acid, interferon-α and radiation therapy compared with concomitant chemo-radiation therapy.
- To determine if there is an immune response to Human Papillomavirus (HPV) by estimating serum IgG1 and IgG2 antibodies against E7 proteins of HPV types 16 and 18 before and after treatment.
The study hypothesis:
- The response rates and survival rates of retinoic acid and interferon-α combination with radiation will be better than chemo-radiation to treat stage III cervical cancer.
- Treatment with the retinoic acid, interferon-α and radiation combination therapy will be less toxic and better tolerated than chemo-radiation therapy.
Detailed description
A total of 200 women with confirmed diagnosis of invasive cervical cancer, stage III, will be recruited into the study. The patients will be recruited from the Gynecologic Oncology Department of the Chittaranjan National Cancer Institute that registers more than 600 cases of cancer of the cervix per year. Computer-generated numbers will randomize patients into the two treatment arms.
This trial is designed to treat stage III cervical cancer patients with concomitant immunotherapy (with cis-retinoic acid and interferon-α) and radiotherapy in the study arm.
Cancer of the uterine cervix is the second most common cancer among women worldwide and is the cause of the largest number of cancer-related deaths among women in the developing countries. In India, cervical cancer is the commonest cancer among women (126,000 new cases, 71,000 deaths in 2000), accounting for more than a quarter of the global burden of cervical cancer (471,000 new cases and 233,000 deaths).1,2 In contrast, in the U.S., although, there were only 12,200 new cases of cervical cancer and 4,100 deaths in 2003, the United States spends $5 billion per year screening and treating cervical cancer and precancerous lesions.
Advanced cervical cancer is relatively rare in the developed world because of routine PAP testing. However, in a developing country like India, because of the absence of any population based cervical cancer screening programs (HPV testing, PAP smears), nearly 80% of the patients are initially detected at stage III or higher. Cisplatin-based chemotherapy administered along with surgery and radiation is the recommended treatment for advanced cervical cancer in the US and other developed countries.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Drug: Interferon, Retinoic Acid and radiationTreatment consists of Interferon, given as a sub-cutaneous injection, 3 times per week for 4 weeks, 20 mg Retinoic Acid tablets, 2 times a day for 30 days. starting from the first day of radiation. |
| Group B | Active comparator | Drug: Cisplatin and radiationTreatment consists of radiation and chemotherapy using Cisplatin. Cisplatin, given intravenously, will be administered on the first day of each week, mixed with saline solution, before and after the Cisplatin infusion. Radiation will be given for a few minutes daily, five days a week, for approximately 5 weeks. Two weeks after completion of external radiotherapy, subject will receive internal radiation (brachytherapy) once a week for two weeks. For this internal radiation a specially designed instrument will be inserted into the vagina that will be connected to a machine for a few minutes. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Advanced cervical cancer
Key exclusion criteria (5 listed)
- Previously treated for cancer of the cervix
- Karnofsky Performance Score less than 50
- Renal dysfunction ( Serum creatinine > 2.0mg/dl)
- Hepatic dysfunction (Serum bilirubin> 2.0 mg/dl, transaminases > 1.5 times normal)
- Pregnant or lactating women: Women will be tested by pregnancy test for possibility of existing pregnancy. Those that meet criteria of trial will be asked to promise that they don't become pregnant; barrier contraception will be recommended.
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 |
|---|---|---|
| Interferon, Retinoic Acid and radiationInterferon-α2b will be administered 3 times a week for four weeks at a dose of 3 x 106 IU subcutaneously concomitant with radiotherapy. The first dose will be administered on the day the subject starts radiotherapy; 13-cis-retinoic acid will be administered orally at a dose of 40 mg/day for 1 month starting from day 1 of radiotherapy; a total of 40 to 45 Gy whole pelvis irradiation will be delivered in conventional fractions to both the study group and the control group. Additional parametrial dosages will be delivered to complete 55 Gy. This will be followed by two intracavitary applications of approximately 40-50 Gy, depending on the volume. | Drug | Group A |
| Cisplatin and radiationWeekly cisplatin will be administered concurrent with external beam radiation at a dose of 40mg/m2/week for 5 weeks; a total of 40 to 45 Gy whole pelvis irradiation will be delivered in conventional fractions. Additional parametrial dosages will be delivered to complete 55 Gy. This will be followed by two intracavitary applications of approximately 40-50 Gy, depending on the volume. | Drug | Group B |
Primary outcome
Survival
Time frame: 3 years or death
Overall survival curves will be computed using the method of Kaplan and Meyer. The difference in survival between the two groups will be compared by log rank test with the O'Brien-Fleming boundaries to control for alpha spending at a planned interim analysis (50% of the total accrual).
3 secondary outcomes
Response rate
Time frame: 3 years or death
Overall toxicity
Time frame: 3 years or death
Determine immune response to Human Papillomavirus HPV
Time frame: 3 years to death
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 29 Dec 2017.
- Derived from this study: PubMed 26700705Basu P, Jenson AB, Majhi T, Choudhury P, Mandal R, Banerjee D, Biswas J, Pan J, Rai SN, Ghim SJ, Miller D. Phase 2 Randomized Controlled Trial of Radiation Therapy Plus Concurrent Interferon-Alpha and Retinoic Acid Versus Cisplatin for Stage III Cervical Carcinoma. Int J Radiat Oncol Biol Phys. 2016 Jan 1;94(1):102-110. doi: 10.1016/j.ijrobp.2015.09.040.
Related trials for Cervical Cancer
Not yet recruitingObservational study
Development and Validation of a Biopsy Decision Model for Nasopharyngeal Carcinoma Based on Serological Markers and Endoscopic Features
Nasopharyngeal Carcinoma (NPC)
RecruitingObservational study
Prospective Comprehensive Molecular Analysis of Endocrine Neoplasms
Endocrine Tumors, Thyroid Neoplasms
Active, not recruitingPhase 2
Study of Proton Versus Photon Beam Radiotherapy in the Treatment of Head and Neck Cancer
Head and Neck Cancer
RecruitingPhase 2
Zemetostat With Anlotinib in Patients With Recurrent/Metastatic Head and Neck Soft Tissue Sarcoma
Soft Tissue Sarcoma
RecruitingObservational study
Genetic Analysis of Pheochromocytomas, Paragangliomas and Associated Conditions
Pheochromocytoma, Paraganglioma
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.
Partha S Basu, MD principal investigator
Chittaranjan National Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Interferon, Retinoic Acid and radiation and Cisplatin and radiation in people with Cervical Cancer, run by University of Louisville 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 1 inclusion and 5 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 29 Dec 2017. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Survival (time frame: 3 years or death). 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 NCT01276730, which also lists 1 linked publication.
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 29 Dec 2017.