A Phase II Study of Extended Field IMRT External Beam Irradiation and Intracavitary Brachytherapy

Cervical Cancer Clinical Trial

Official title:

A Phase II Study of Extended Field IMRT External Beam Irradiation and Intracavitary Brachytherapy With Concurrent Weekly Cisplatin in Patients With Stage I-IVA Cervical Cancer Who Have FDG PET Positive Pelvic or Para-Aortic Lymph Nodes

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00590967
• Other study ID #: 03-0300 / 201105362
• Status: Terminated
• Phase: Phase 2
• First received: December 31, 2007
• Last updated: August 2, 2013
• Start date: May 2003
• Est. completion date: January 2013

Study information

• Verified date: August 2013
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Recent studies have shown that the chance of survival among women with advanced cervical cancer is increased when they receive concurrent chemotherapy and radiation to the pelvis. However, patients who have advanced disease show loco-regional failure as well as a high incidence of distant metastasis. PET scanning has high sensitivity and specificity in the detection of pelvic and para-aortic lymph node metastases. While the detection of para-aortic metastases by PET significantly impacts prognosis, PET has been known to show positive lymph node metastasis in the pelvis only while not detecting micrometastatic disease in the para-aortic lymph nodes (despite the fact that they are histologically known).

In addition, patients with positive para-aortic lymph nodes on PET, greater amounts (more than 45 Gy) of radiation must be used to improve the probability of controlling the cancer. However, doses greater than this have been limited because of the dose and volume limits to the small bowel. But, Intensity Modulated Radiation Therapy (IMRT) is a new way of calculating and delivering radiation therapy. Compared to external beam radiation, IMRT has the improved ability to deliver large doses of radiation to specific targets while minimizing the exposure to surrounding normal tissue.

With IMRT, however, the effective dose/volume can be increased more safely and lower the toxicity of surrounding tissue, thus making prophylactic dosing to para-aortic lymph nodes not detected by PET safer and more effective.

Description:

Prior to entrance on the study, patients will undergo a history and physical and evaluation of Karnofsky Performance Status. They will have a biopsy of their tumor and will undergo a FDG PET scan and must include evaluation of para-aortic lymph nodes. Blood work will be done (CBC, differential, platelets. BUN, serum creatinine, bilirubin, AST, ALT and alkaline phosphatase. Also, pre-treatment, patients will receive a chest x-ray and an IVP (unless a CT with contrast has been performed). Additionally, patient may undergo a CT, MRI and/or lymphangiogram.

Patients will then be registered to a treatment arm, depending on the outcome of their PET scan. Patients with positive pelvic lymph nodes but no positive para-aortic lymph nodes by PET will be assigned to Treatment Arm 1. Patients with positive pelvic lymph nodes and positive para-aortic lymph nodes by PET will be assigned to treatment arm 2.

Treatment Group 1. Either a conventional or CT simulation may be performed. Patients will be treated with IMRT extended field external beam radiation therapy (to cover pelvis and para-aortic lymph nodes) and intracavitary radiation (6 HDR treatments) concurrently with cisplatin (40 mg/m2/week)

Treatment Group 2. A CT simulation must be performed. Patients will be treated with extended field external beam radiation therapy to the pelvis and with IMRT to cover the para-aortic lymph nodes to 60 Gy, 50.4 Gy to the para-aortic lymph node bed in conjunction with external beam pelvic radiation therapy as appropriate for disease stage and intracavitary radiation (6 HDR treatments) concurrently with cisplatin (40 mg/m2/week).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 69
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have carcinoma of the uterine cervix.

• Patients with squamous cell, adenocarcinoma, and adenosquamous carcinoma are eligible.

• FIGO Stage I to IVA

• Patients must have no evidence of metastatic disease outside of the pelvis (except to the para-aortic nodes), by PET.

• Patients must have a Karnofsky Performance Status of >= 60 and no medical contraindications to the administration of chemotherapy.

• Age >= 18.

• Adequate bone marrow function: WBC >= 4000/mm3, platelets >= 100,000 mm3.

• Adequate renal function: BUN <= 25 mg/dl, creatinine <= 1.2 mg/dl (urinary diversion is permitted to improve renal function).

• Patients must have bilirubin <= 1.5 mg/dl.

• Signed study-specific informed consent.

Exclusion Criteria:

• No positive lymph nodes by FDG PET

• Positive supraclavicular lymph nodes by FDG PET Scan or evidence of more distant disease.

• FIGO Stage IVB+ Cervical Cancer

• No prior (within 5 years) or simultaneous malignancies (other than cutaneous basal cell carcinoma).

• Karnofsky Performance Status <60.

• Patients with significant medical illness preventing the use of full dose chemotherapy are excluded.

• Patients with the following histologies are excluded: small cell, carcinoid, glassy cell, clear cell and adenoid cystic.

• Life expectancy < 6 months.

• Patients with poorly controlled diabetes mellitus (fasting blood glucose level > 200 mg/dL) are not eligible.

• No prior surgery for treatment of disease other than exploratory laparotomy or biopsy.

• No previous systemic chemotherapy.

• No pelvic radiation therapy is permitted other than transvaginal irradiation to control bleeding.

• Pregnant women are ineligible and those of child-bearing potential should practice contraception.

• Patients with abnormal liver function tests

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cervical Cancer
• Uterine Cervical Neoplasms

Intervention

Radiation:
• IMRT extended field external beam radiation therapy

• Brachytherapy

Drug:
• Cisplatin

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Group 1 - Tolerance of IMRT extended-field external radiotherapy to pelvis and para-aortic region, combined with intracavitary irradiation, and cisplatin chemotherapy.		1 year post start of radiation therapy	Yes
Primary	Group 1 - Acute toxicity of IMRT extended-field external radiotherapy to pelvis and para-aortic region, combined with intracavitary irradiation, and cisplatin chemotherapy.		30 days after completion of radiation therapy	Yes
Primary	Group 1 - Efficacy of IMRT extended-field radiation combined with intracavitary irradiation, and cisplatin chemotherapy	As evidenced by tumor control and the frequency of distant metastasis	5 years after completion of radiation therapy	No
Primary	Group 2 - Feasibility and tolerance of IMRT to the para-aortic lymph nodes, IMRT external beam radiotherapy to the pelvis, intracavitary irradiation and cisplatin chemotherapy		1 year post start of radiation therapy	Yes
Primary	Group 2 - Acute toxicity of IMRT to the para-aortic lymph nodes, IMRT external beam radiotherapy to the pelvis, intracavitary irradiation, and cisplatin chemotherapy		30 days after completion of radiation therapy	Yes
Primary	Group 2 - Efficacy of IMRT to the para-aortic lymph nodes, IMRT external beam radiotherapy to the pelvis, intracavitary irradiation, and cisplatin chemotherapy	As evidenced by tumor control and the frequency of distant metastasis	5 years after completion of radiation therapy	No
Secondary	Group 1 & 2 - Assess the utility of post-treatment FDG PET scan for surveillance detection of lymphatic and distant metastases and correlate these findings with outcome.		90-120 days after completion of all therapy	Yes

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine