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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2012 by University of California, San Diego
Sponsor:
Information provided by (Responsible Party):
Loren Mell, MD, University of California, San Diego
ClinicalTrials.gov Identifier:
NCT01554410
First received: March 8, 2012
Last updated: July 20, 2013
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Cervical Carcinoma
Radiation: Intensity Modulated Radiation Therapy (IMRT)
Drug: Cisplatin
Drug: Gemcitabine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of Intensity Modulated Radiation Therapy With Concurrent Cisplatin and Escalating Gemcitabine for Locally Advanced Cervical Carcinoma

Resource links provided by NLM:


Further study details as provided by University of California, San Diego:

Primary Outcome Measures:
  • Establish the maximum tolerated dose (MTD) of Gemcitabine that can be safely administered in combination with Cisplatin [ Time Frame: 5 weeks during treatment ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Number of Participants with Acute Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 30 Days post-treatment ] [ Designated as safety issue: Yes ]
    To quantify acute treatment-related adverse events that occur within 30 days of completing protocol treatment.

  • Number of Participants with Progression-Free Survival as a Measure of Response [ Time Frame: Up to 12 months post treatment ] [ Designated as safety issue: No ]
    To determine the progression-free and overall survival of patients treated with gemcitabine at the MTD in this regimen.


Estimated Enrollment: 18
Study Start Date: August 2010
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    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)
    Drug: Gemcitabine
    Weekly infusion x 5 weeks at escalating dose levels (50mg/m2, 75mg/m2, 100mg/m2, and 125mg/m2)
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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01554410

Contacts
Contact: Mary Wright 858-822-5367 mewright@ucsd.edu
Contact: Meaghan Stirn 858-822-5354 mstirn@ucsd.edu

Locations
United States, California
Moores UC San Diego Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Carrie Marcus    858-822-5036    cjrichardson@ucsd.edu   
Principal Investigator: Loren Mell, MD         
Sub-Investigator: Arno Mundt, MD         
Sub-Investigator: Catheryn Yashar, MD         
Sub-Investigator: Mary Ann Rose, MD         
Sub-Investigator: Steven Plaxe, MD         
Sub-Investigator: Michael McHale, MD         
Sub-Investigator: Cheryl Saenz, MD         
Sponsors and Collaborators
University of California, San Diego
Investigators
Principal Investigator: Loren Mell, MD University of California, San Diego
  More Information

Additional Information:
No publications provided

Responsible Party: Loren Mell, MD, Assistant Professor, Director Division, University of California, San Diego
ClinicalTrials.gov Identifier: NCT01554410     History of Changes
Other Study ID Numbers: UCSD 100597
Study First Received: March 8, 2012
Last Updated: July 20, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, San Diego:
Cervical
Carcinoma
Gemcitabine
Gemzar
Cisplatin
IMRT
Radiation
External Beam
Brachytherapy

Additional relevant MeSH terms:
Carcinoma
Uterine Cervical Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Gemcitabine
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on July 24, 2014