Advanced Cervical Cancer Trial in India

December 27, 2017 updated by: University of Louisville

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

209

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
      • Kolkata, India, 700026
        • Chittaranjan National Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Advanced cervical cancer

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
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.
Drug: Interferon, Retinoic Acid and radiation
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.
Active Comparator: Group B

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.
Drug: Cisplatin and radiation
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 years or death

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rate
Time Frame: 3 years or death
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.
3 years or death
Overall toxicity
Time Frame: 3 years or death
Fisher's exact test will be used to compare the incidences of WHO toxicities and response rates between the treatment groups.
3 years or death
Determine immune response to Human Papillomavirus HPV
Time Frame: 3 years to death
By estimating serum IgGl and IgG2 antibodies against E7 protein of HPV types 16 and 18 before and after treatment.
3 years to death

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Louisville

Collaborators

James Graham Brown Cancer Center

Investigators

  • Principal Investigator: Partha S Basu, MD, Chittaranjan National Cancer Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2007

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

November 2, 2010

First Submitted That Met QC Criteria

January 12, 2011

First Posted (Estimate)

January 13, 2011

Study Record Updates

Last Update Posted (Actual)

December 29, 2017

Last Update Submitted That Met QC Criteria

December 27, 2017

Last Verified

December 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 464.05

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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