Clinical trial NCT01554410: Intensity Modulated Radiation Therapy With Cisplatin and Gemcitabine to Treat Locally Advanced Cervical Carcinoma
Official title: A Phase I Trial of Intensity Modulated Radiation Therapy With Concurrent Cisplatin and Escalating Gemcitabine for Locally Advanced Cervical Carcinoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Carcinoma
Keywords: Cervical
Carcinoma
Gemcitabine
Gemzar
Cisplatin
IMRT
Radiation
External Beam
Brachytherapy
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2012-03-15
Enrollment: 35
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Establish the maximum tolerated dose (MTD) of Gemcitabine that can be safely administered in combination with Cisplatin
timeFrame: 5 weeks during treatment
Secondary outcomes:
measure: Number of Participants with Acute Adverse Events as a Measure of Safety and Tolerability
timeFrame: Up to 30 Days post-treatment
measure: Number of Participants with Progression-Free Survival as a Measure of Response
timeFrame: Up to 12 months post treatment
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Moores UC San Diego Cancer Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Loren Mell, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.