Intensity Modulated Radiation Therapy With Cisplatin and Gemcitabine to Treat Locally Advanced Cervical Carcinoma

Study Overview
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Brief Summary
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The primary objective of the study is to identify the highest dose of gemcitabine that can be given safely with cisplatin and pelvic intensity modulated radiation therapy (IMRT) in women with locally advanced cervical cancer. The investigators hypothesis is that IMRT will reduce gastrointestinal and hematologic toxicity, permitting escalating doses of gemcitabine to be feasibly delivered in patients with locally advanced cervical cancer.

Detailed Description
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Many studies have investigated multiagent chemotherapy as a means of intensifying treatment. The results of such trials indicate that gemcitabine has considerable activity against cervical cancer when given with cisplatin/RT, however, it is quite toxic. The predominant toxicities are gastrointestinal and hematologic. Methods to reduce gastrointestinal and hematologic toxicity during chemoradiotherapy could mitigate this toxicity and take advantage of the therapeutic benefits of gemcitabine IMRT is an advanced radiation therapy delivery technique that reduces the amount of radiation given to normal tissues and may therefore reduce unwanted side effects. IMRT tries to lower the amount of radiation that normal tissues receive, while still delivering the desired amount of radiation to the cancer cells and other areas, such as lymph nodes. IMRT does this by using computers to design the best way to aim radiation at the tumor(s), while still delivering a radiation dose comparable to standard radiation.

Official Title
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A Phase I Trial of Intensity Modulated Radiation Therapy With Concurrent Cisplatin and Escalating Gemcitabine for Locally Advanced Cervical Carcinoma

Conditions
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Cervical Carcinoma

Intervention / Treatment
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* Radiation: Intensity Modulated Radiation Therapy (IMRT)
* Drug: Cisplatin
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis: Histologically-proven, invasive primary carcinoma of the cervix. Disease Status: Stage IB2-IVA cervical cancer or stage I with biopsy-proven pelvic node metastases, positive surgical margins, or parametrial extension based upon standard diagnostic workup, including: History/physical examination Examination under anesthesia (if indicated) Biopsy Intravenous pyelogram and/or cystoscopy (if indicated) Colonoscopy, sigmoidoscopy, or rigid proctoscopy (if indicated) PA and lateral chest x-ray or chest CT CT or MRI of the pelvis PET, PET/CT, or PET/CT simulation (encouraged) Performance Level: Karnofsky Performance Status ≥ 60 - Peripheral ≥ ANC 1500/uL Platelet count ≥ 100,000/uL (transfusion independent) Hemoglobin ≥ 8.0 g/dL (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable) Serum creatinine ≤ 1.5 mg/dl Bilirubin (sum of conjugated + unconjugated) < 1.5 mg/dl, and SGPT (ALT) < 1.5 x upper limit of normal (ULN) for age, and SGOT (AST) < 1.5 x upper limit of normal (ULN) for age Exclusion Criteria: Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to risks of fetal and teratogenic adverse events.(Note: Serum Pregnancy tests must be obtained in women of child bearing potential). Sexually active females may not participate unless they have agreed to use an effective contraceptive method (such as abstinence, diaphragm, condom, or intrauterine device) to prevent pregnancy for the duration of the study. Concomitant Medications, if taken within the last 28 days. Growth factor(s): Growth factors that support platelet or white cell number or function must not have been administered within the past 28 days. Erythropoietic drug(s): Erythropoietin or related hormones must not have been administered within the past 28 days. Infection: Patients who have an uncontrolled infection. Evidence of para-aortic lymphadenopathy or distant metastases Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years. Prior systemic chemotherapy within the last three years. Prior radiotherapy to the pelvis Allergic to iodinated contrast if undergoing a contrast enhanced CT scan of the pelvis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMRT/Cisplatin/Gemcitabine<br>All patients get IMRT with concurrent cisplatin & gemcitabine, with the dose of gemcitabine varying according to cohort | Radiation: Intensity Modulated Radiation Therapy (IMRT)<br>* 45 Gy in 25 daily fractions (1.8 Gy per fraction)<br>Drug: Cisplatin<br>* Weekly infusion of 40 mg/m2 x 5 weeks (70 mg maximum)<br>Drug: Gemcitabine<br>* Weekly infusion x 5 weeks at escalating dose levels (50mg/m2, 75mg/m2, 100mg/m2, and 125mg/m2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establish the maximum tolerated dose (MTD) of Gemcitabine that can be safely administered in combination with Cisplatin | To determine the maximum tolerated dose (MTD) of weekly gemcitabine that can be administered with concurrent weekly cisplatin and pelvic intensity modulated radiation therapy (IMRT) in women with locally advanced cervical cancer | 5 weeks during treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Acute Adverse Events as a Measure of Safety and Tolerability | To quantify acute treatment-related adverse events that occur within 30 days of completing protocol treatment. | Up to 30 Days post-treatment | 
| Number of Participants with Progression-Free Survival as a Measure of Response | To determine the progression-free and overall survival of patients treated with gemcitabine at the MTD in this regimen. | Up to 12 months post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiation, Cervical, Carcinoma, Gemcitabine, Gemzar, Cisplatin, IMRT, External Beam, Brachytherapy