Clinical trial NCT01276730: Advanced Cervical Cancer Trial in India
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Keywords: Advanced cervical cancer
India
Lead sponsor: University of Louisville
Sponsor class: OTHER
Collaborators: name: James Graham Brown Cancer Center
First posted: 2011-01-13
Enrollment: 209
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.
* 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.

Eligibility 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.

Primary outcomes:
measure: Survival
timeFrame: 3 years or death
Secondary outcomes:
measure: Response rate
timeFrame: 3 years or death
measure: Overall toxicity
timeFrame: 3 years or death
measure: Determine immune response to Human Papillomavirus HPV
timeFrame: 3 years to death
Other outcomes:
Locations:
city: Kolkata
country: India
facility: Chittaranjan National Cancer Institute
Study officials:
affiliation: Chittaranjan National Cancer Institute
name: Partha S Basu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.