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

Cervical Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01554410
• Other study ID #: UCSD 100597
• Status: Completed
• Phase: Phase 1
• Start date: August 2010
• Est. completion date: August 1, 2020

Study information

• Verified date: February 2022
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: August 1, 2020
• Est. primary completion date: July 16, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Cervical Carcinoma

Intervention

Radiation:
• Intensity Modulated Radiation Therapy (IMRT)
45 Gy in 25 daily fractions (1.8 Gy per fraction)

Drug:
• Cisplatin
Weekly infusion of 40 mg/m2 x 5 weeks (70 mg maximum)
• Gemcitabine
Weekly infusion x 5 weeks at escalating dose levels (50mg/m2, 75mg/m2, 100mg/m2, and 125mg/m2)

Locations

Country	Name	City	State
United States	Moores UC San Diego Cancer Center	La Jolla	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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

External Links

•   UC San Diego Department of Radiation Medicine & Applied Sciences