Study on Early Stage Bulky Cervical Cancers

Randomised Phase III Clinical Trial on Concurent Chemoradiation vs. Neoadjuvant Chemoradiation and Surgery vs. Neoadjuvant Chemotherapy and Surgery in Early Stage Bulky Cervical Cancers (FIGO Stages IB2, IIA2 and IIB)

The aim of this study is to establish the role of neoadjuvant chemotherapy and chemo irradiation in carcinoma cervix and to compare its results with the concurrent chemo irradiation in terms of overall survival, disease free survival and quality of life.

Study Overview

• Status: Unknown
• Conditions: Carcinoma Cervix
• Intervention / Treatment: Drug: Chemotherapy; Radiation: External Beam Radiotherapy; Radiation: Brachytherapy; Procedure: Radical Hysterectomy

Detailed Description

Early stage bulky cancers of the cervix, (defined as FIGO Stages IB2, IIA2 and IIB) form a distinctive subset of "curable" cervical cancers with good 5 year survival rates with adequate treatment. Concurrent chemo radiation with or without salvage surgery is at present the standard of care for this group of cervical cancers. However, when pelvic recurrences occur, the morbidity of salvage surgery after radiotherapy, especially brachytherapy is often higher than the morbidity of salvage radiotherapy following radical surgery. The advantages of downsizing the disease without the use of brachytherapy are tempting and open a completely new philosophy in radical treatment for "curable" early stage bulky cancers of the cervix. This approach is appealing especially in developing countries where the load of cervical cancers is high and radiotherapy (brachytherapy) resources are scarce.

The results of two Phase II trials conducted at Govt. Royapettah Hospital, Chennai (Neoadjuvant Chemotherapy followed by Radical Hysterectomy: Cisplatin + 5FU vs. Cisplatin +Paclitaxel) and at Govt. General Hospital,Chennai (Neoadjuvant Chemoradiation with weekly cisplatin and 50 EBRT followed by radical Hysterectomy) and one retrospective study ( Preoperative 50 GY EBRT followed by Radical Hysterectomy) have shown similar response rates and acceptable toxicity profiles when compared to concurrent chemoradiation (EBRT + Brachytherapy+ Chemotherapy). Similar studies have been published elsewhere with similar results.

With this in mind we are planning to conduct a Phase III Randomised control trial comparing Neoadjuvant Chemotherapy + Radical Hysterectomy and Neoadjuvant Chemoradiation + Radical Hysterectomy with concurrent chemoradiation in this subset of cervical cancers

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 600014IndiaNaduI6
      • Recruiting
      • Government Royapettah Hospital
      • Contact: Rajaraman Ramamurthy, MS MCh; Phone Number: +919444046168; Email: rajaanu1@rediffmail.com
      • Contact: Subbiah Shanmugam, MS MCh; Phone Number: +919360206030; Email: subbiah_doctor@yahoo.co.uk
      • Principal Investigator: Rajaraman Ramamurthy, MS MCh
      • Sub-Investigator: Subbiah Shanmugam, MS MCh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients with histologically confirmed bulky cervical Squamous cell carcinoma (FIGO stage IB2, II A2, IIB).
2. Age 18-60 years
3. Karnofsky performance status of ≥70%; ECOG PS ≤ 2

Exclusion Criteria:

1. Nonsquamous Histologies
2. Other systemic diseases, comorbidities precluding full participation in the study
3. Concomitant treatment with any experimental drug
4. Pregnant or nursing women
5. Previous or concomitant malignant diseases other than non-melanoma skin cancer
6. Previous radiation to the pelvis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Concurrent Radical Chemoradiation; Paclitaxel(175 mg/sq.m) + Cisplatin (75 mg/sq.m) chemotherapy - 2 cycles of 3 weekly cycle Concurrent Radiotherapy - 50 Gy EBRT + Brachytherapy (7Gy HDR x 3 doses) All to be completed within 8-10 weeks	Drug: Chemotherapy; cisplatin 75 mg/m2 Paclitaxel 175 mg/m2; Radiation: External Beam Radiotherapy; 50 Gy/2 Gy/25 # external beam RT to cervix. four field technique. given concurrently with chemotherapy weeks 1 - 5; Radiation: Brachytherapy; Ir - 192 HDR Brachytherapy - intracavitary. 7Gy x 3#. given after completion of chemoRT.
EXPERIMENTAL: Neoadjuvant Chemoradiation + Radical Hysterectomy; Paclitaxel(175 mg/m2) + Cisplatin(75 mg/m2) chemotherapy - 2 cycles of 3 weekly cycle Concurrent Radiotherapy - 50 Gy EBRT - completed within 5 weeks Radical Hysterectomy - 3 weeks after completion of RT All to be completed within 8-10 weeks	Drug: Chemotherapy; cisplatin 75 mg/m2 Paclitaxel 175 mg/m2; Radiation: External Beam Radiotherapy; 50 Gy/2 Gy/25 # external beam RT to cervix. four field technique. given concurrently with chemotherapy weeks 1 - 5; Procedure: Radical Hysterectomy; Type III Radical Hysterectomy + Bilateral Pelvic Node Dissection
EXPERIMENTAL: Neoadjuvant Chemotherapy + Radical Hysterectomy; Paclitaxel(175 mg/m2) + Cisplatin (75 mg/m2) chemotherapy - 3 cycles of 3 weekly cycle Radical Hysterectomy - 3 weeks after completion of chemotherapy All to be completed within 8-10 weeks	Drug: Chemotherapy; cisplatin 75 mg/m2 Paclitaxel 175 mg/m2; Procedure: Radical Hysterectomy; Type III Radical Hysterectomy + Bilateral Pelvic Node Dissection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall and Disease free Survival	3 year
Overall and Disease free Survival	5 year

Secondary Outcome Measures

Outcome Measure	Time Frame
Acute Adverse reactions and complications	Less than 10 weeks
SubAcute Adverse reactions and complications	10 weeks - 6 months
Chronic Adverse reactions and complications	6 months to 5 years

Other Outcome Measures

Outcome Measure	Time Frame
Quality of Life	3,5 years

Collaborators and Investigators

• Sponsor: Rajkumar Kottayasamy Seenivasagam
• Investigators: Study Chair: Rajaraman Ramamurthy, MS MCh, centre for oncology, Government Royapettah Hospital

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ANTICIPATED): August 1, 2018
• Study Completion (ANTICIPATED): August 1, 2018

Study Registration Dates

• First Submitted: August 3, 2013
• First Submitted That Met QC Criteria: August 5, 2013
• First Posted (ESTIMATE): August 7, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): August 13, 2015
• Last Update Submitted That Met QC Criteria: August 11, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Neoadjuvant Chemotherapy; Neoadjuvant Chemoradiotherapy; Bulky cervical cancers
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms
• Other Study ID Numbers: GRHCO-01