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

NCT01554410 | Completed Phase 1 DMC

• 1 other identifier: UCSD 100597
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Cervical Carcinoma

Keywords

Cervical; Carcinoma; Gemcitabine; Gemzar; Cisplatin; IMRT; Radiation; External Beam; Brachytherapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Number of Participants with Acute Adverse Events as a Measure of Safety and Tolerability

  Up to 30 Days post-treatment

• Number of Participants with Progression-Free Survival as a Measure of Response

  Up to 12 months post treatment

Study Arms (1)

IMRT/Cisplatin/Gemcitabine

EXPERIMENTAL

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

Radiation: Intensity Modulated Radiation Therapy (IMRT); Drug: Cisplatin; Drug: Gemcitabine

Interventions

Intensity Modulated Radiation Therapy (IMRT) RADIATION

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

IMRT/Cisplatin/Gemcitabine

Cisplatin DRUG

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

IMRT/Cisplatin/Gemcitabine

Gemcitabine DRUG

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

IMRT/Cisplatin/Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

Moores UC San Diego Cancer Center

La Jolla, California, 92093, United States

Location

Related Publications (1)

• 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.

  PMID: 32334034 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Carcinoma

Interventions

Radiotherapy, Intensity-Modulated; Cisplatin; Gemcitabine

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Loren Mell, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 8, 2012
• First Posted: March 15, 2012
• Study Start: August 1, 2010
• Primary Completion: July 16, 2019
• Study Completion: August 1, 2020
• Last Updated: February 17, 2022

Record last verified: 2022-02

Locations

US (1)