Paclitaxel and Carboplatin Followed by Cisplatin and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

Phase II Study of Weekly Neoadjuvant Chemotherapy Followed by Radical Chemoradiation for Locally Advanced Cervical Cancer

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, carboplatin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving paclitaxel together with carboplatin followed by cisplatin and radiation therapy works in treating patients with stage IB, stage II, stage III, or stage IVA cervical cancer.

Study Overview

• Status: Unknown
• Conditions: Cervical Cancer
• Intervention / Treatment: Drug: carboplatin; Radiation: radiation therapy; Procedure: neoadjuvant therapy; Drug: cisplatin; Drug: paclitaxel; Radiation: brachytherapy

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate, in terms of clinical or radiologic response at 12 weeks after completion of study therapy, in patients with stage IB2-IVA cervical cancer treated with neoadjuvant chemotherapy comprising dose-dense paclitaxel and carboplatin followed by radical chemoradiotherapy comprising concurrent cisplatin and radiotherapy.

Secondary

• Determine the response rate in patients treated with this neoadjuvant chemotherapy regimen.
• Determine the toxicity of this neoadjuvant chemotherapy regimen in these patients.
• Assess the progression-free survival of patients treated with this regimen.
• Determine the overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Neoadjuvant chemotherapy: Patients receive neoadjuvant chemotherapy comprising paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on day 1. Treatment repeats weekly for up to 6 courses in the absence of disease progression or unacceptable toxicity.
• Chemoradiotherapy: Beginning in week 7, or as soon as blood counts recover, patients receive cisplatin IV over 1 hour on day 1. Treatment repeats weekly for 4-6 courses in the absence of disease progression or unacceptable toxicity. Patients also undergo concurrent radiotherapy comprising pelvic external beam radiotherapy once daily for 5½ weeks (5 weeks for patients with positive para-aortic lymph nodes) and 2 applications of high-dose rate intracavitary brachytherapy or low- or medium-dose rate brachytherapy. Patients with parametrial or pelvic sidewall disease extension also undergo external boost radiotherapy for 3 days.

After completion of study therapy, patients are followed periodically for 2 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • England
    • Leicester, England, United Kingdom, LE1 5WW
      • Recruiting
      • Leicester Royal Infirmary
      • Contact: R. Paul Symonds, MD, FRCP, FRCR; Phone Number: 44-116-258-6296
    • London, England, United Kingdom, SW3 6JJ
      • Recruiting
      • Royal Marsden - London
      • Contact: Peter R. Blake, MD; Phone Number: 44-20-7808-2581; Email: peter.blake@rmh.nthames.nhs.uk
    • London, England, United Kingdom, WIT 3AA
      • Recruiting
      • University College of London Hospitals
      • Contact: Mary McCormack, MD; Phone Number: 44-20-7380-9302

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed carcinoma of the cervix, including any of the following subtypes:

  • Squamous cell carcinoma
  • Adenocarcinoma
  • Adenosquamous cell carcinoma

• Locally advanced disease (i.e., FIGO stage IB2-IVA disease)

  • Stage confirmed by examination under anesthesia, cystoscopy, and sigmoidoscopy with biopsy of any suspicious lesions in the bladder, vagina, or rectum
• Disease suitable for treatment with radical intent using chemoradiotherapy

PATIENT CHARACTERISTICS:

• ECOG performance status 0-1
• Platelet count > 100,000/mm^3
• Hemoglobin > 12.5 g/dL
• WBC > 3,000/mm^3
• Absolute neutrophil count > 1,500/mm^3
• Bilirubin < 1.25 times upper limit of normal (ULN)
• Glomerular filtration rate (GFR) normal by ethylenediaminetetraacetic acid (EDTA) OR creatinine clearance ≥ 60 mL/min
• Placement of ureteric stents required for all patients with hydronephrosis, regardless of renal function
• ALT or AST < 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• No prior diagnosis of cancer, except basal cell skin cancer
• No active cardiac disease
• Deemed fit to receive chemoradiotherapy
• ECG normal

PRIOR CONCURRENT THERAPY:

• Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate at the end of chemoradiotherapy (i.e., 12 weeks after completion of study therapy)

Secondary Outcome Measures

Outcome Measure
Progression-free survival
Overall survival
Toxicity as assessed by NCI CTCAE v3.0
Response rate at the end of neoadjuvant treatment (i.e., 6 weeks after study entry)

Collaborators and Investigators

• Sponsor: University College London Hospitals
• Investigators: Study Chair: Mary McCormack, MD, University College London Hospitals

Study record dates

Study Major Dates

• Study Start: June 1, 2005

Study Registration Dates

• First Submitted: April 18, 2007
• First Submitted That Met QC Criteria: April 18, 2007
• First Posted (Estimate): April 19, 2007

Study Record Updates

• Last Update Posted (Estimate): August 26, 2013
• Last Update Submitted That Met QC Criteria: August 23, 2013
• Last Verified: April 1, 2007

More Information

Terms related to this study

• Keywords: cervical squamous cell carcinoma; stage IIB cervical cancer; stage III cervical cancer; stage IVA cervical cancer; stage IB cervical cancer; stage IIA cervical cancer; recurrent cervical cancer; cervical adenocarcinoma; cervical adenosquamous cell carcinoma
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Uterine Cervical Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel; Cisplatin
• Other Study ID Numbers: CDR0000540233; UCLCTC-BRD/05/22-CERVIX; EUDRACT-2005-000134-20; CRUK-BRD/05/22; EU-20720; UCLCTC-CERVIX