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Advanced Cervical Cancer Trial in India

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Louisville
Information provided by (Responsible Party):
James Graham Brown Cancer Center
ClinicalTrials.gov Identifier:
NCT01276730
First received: November 2, 2010
Last updated: April 23, 2014
Last verified: April 2014
  Purpose

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.

Condition Intervention Phase
Cervical Cancer
Drug: Interferon, Retinoic Acid and radiation
Drug: Cisplatin and radiation
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by James Graham Brown Cancer Center:

Primary Outcome Measures:
  • Survival [ Time Frame: 3 years or death ] [ Designated as safety issue: Yes ]
    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).


Secondary Outcome Measures:
  • Response rate [ Time Frame: 3 years or death ] [ Designated as safety issue: No ]
    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.

  • Overall toxicity [ Time Frame: 3 years or death ] [ Designated as safety issue: Yes ]
    Fisher's exact test will be used to compare the incidences of WHO toxicities and response rates between the treatment groups.

  • Determine immune response to Human Papillomavirus HPV [ Time Frame: 3 years to death ] [ Designated as safety issue: No ]
    By estimating serum IgGl and IgG2 antibodies against E7 protein of HPV types 16 and 18 before and after treatment.


Estimated Enrollment: 200
Study Start Date: October 2007
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT01276730

Locations
India
Chittaranjan National Cancer Institute
Kolkata, India, 700026
Sponsors and Collaborators
James Graham Brown Cancer Center
University of Louisville
Investigators
Principal Investigator: Partha S Basu, MD Chittaranjan National Cancer Institute
  More Information

No publications provided

Responsible Party: James Graham Brown Cancer Center
ClinicalTrials.gov Identifier: NCT01276730     History of Changes
Other Study ID Numbers: 464.05
Study First Received: November 2, 2010
Last Updated: April 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by James Graham Brown Cancer Center:
Advanced cervical cancer
India

Additional relevant MeSH terms:
Uterine Cervical Neoplasms
Genital Neoplasms, Female
Neoplasms
Neoplasms by Site
Urogenital Neoplasms
Uterine Cervical Diseases
Uterine Neoplasms
Genital Diseases, Female
Uterine Diseases
Cisplatin
Interferons
Tretinoin
Anti-Infective Agents
Antineoplastic Agents
Antiviral Agents
Dermatologic Agents
Keratolytic Agents
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014