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

NCT ID: NCT01554410

Last Updated: 2022-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2020-08-01

Brief 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.

Detailed 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.

Conditions

Cervical Carcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMRT/Cisplatin/Gemcitabine

All patients get IMRT with concurrent cisplatin \& gemcitabine, with the dose of gemcitabine varying according to cohort

Group Type: EXPERIMENTAL

Intensity Modulated Radiation Therapy (IMRT)

Intervention Type: RADIATION

45 Gy in 25 daily fractions (1.8 Gy per fraction)

Cisplatin

Intervention Type: DRUG

Weekly infusion of 40 mg/m2 x 5 weeks (70 mg maximum)

Gemcitabine

Intervention Type: DRUG

Weekly infusion x 5 weeks at escalating dose levels (50mg/m2, 75mg/m2, 100mg/m2, and 125mg/m2)

Interventions

Intensity Modulated Radiation Therapy (IMRT)

45 Gy in 25 daily fractions (1.8 Gy per fraction)

Intervention Type: RADIATION

Cisplatin

Weekly infusion of 40 mg/m2 x 5 weeks (70 mg maximum)

Intervention Type: DRUG

Gemcitabine

Weekly infusion x 5 weeks at escalating dose levels (50mg/m2, 75mg/m2, 100mg/m2, and 125mg/m2)

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Loren Mell, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Loren Mell, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

Moores UC San Diego Cancer Center

La Jolla, California, United States

Countries

United States

References

Mell LK, Xu R, Yashar CM, McHale MT, Einck JP, Mayadev J, Lee E, Binder P, Rash D, Eskander R, Heide ES, Plaxe SC, Mundt AJ, Saenz CC. Phase 1 Trial of Concurrent Gemcitabine and Cisplatin with Image Guided Intensity Modulated Radiation Therapy for Locoregionally Advanced Cervical Carcinoma. Int J Radiat Oncol Biol Phys. 2020 Aug 1;107(5):964-973. doi: 10.1016/j.ijrobp.2020.04.019. Epub 2020 Apr 22.

Reference Type: DERIVED

PMID: 32334034 (View on PubMed)

Other Identifiers

UCSD 100597

Identifier Type: -

Identifier Source: org_study_id