Study With Intensity Modulated Radiation Therapy With Cisplatin to Treat Stage I-IVA Cervical Cancer

NCT ID: NCT01554397

Last Updated: 2024-11-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-13
• Study Completion Date: 2022-01-01

Brief Summary

The purpose of this study is to find out whether patients with cervical cancer treated with PET-guided Bone Marrow Sparing IMRT have less side effects with equal cancer control compared to standard radiation techniques (IMRT). The hypothesis is that PET-guided Bone Marrow Sparing IMRT will reduce acute hematologic and gastrointestinal toxicity and increase chemotherapy tolerance for cervical cancer patients treated with concurrent cisplatin.

Detailed Description

Multiple randomized controlled trials have established concurrent cisplatin-based chemoradiotherapy as the standard of care for locally advanced cervical cancer [3-8]. The addition of concurrent cisplatin to radiotherapy (RT) increases pelvic control, disease-free survival (DFS) and overall survival; however, 5-year DFS and overall survival are still only approximately 60% and 5-year pelvic failure is approximately 30%. Moreover, acute gastrointestinal (GI) and hematologic toxicity are increased. Approximately 30% of patients will experience acute grade ≥ 3 toxicity, predominantly GI and hematologic. Methods to reduce toxicity during chemoradiotherapy, particularly gastrointestinal and hematologic, could mitigate this toxicity and take advantage of the therapeutic benefits of intensive concurrent chemotherapy.

Intensity modulated radiation therapy (IMRT) is a modern RT technique that differs from conventional techniques in many ways. First, patients undergo computed tomography (CT) simulation so that customized target volumes can be defined 3-dimensionally. IMRT treatment planning involves multiple beam angles and uses computerized inverse treatment planning optimization algorithms to identify dose distributions and intensity patterns that conform dose to the target, reducing radiation dose to surrounding tissues. IMRT delivery is typically accomplished with the use of multileaf collimators, which involve small motorized leaflets (collimators) that move in and out of the beam path, modulating the dose intensity.

PET-guided Bone Marrow Sparing IMRT is designed to spare hematopoietically active subregions of the pelvic bone marrow using quantitative image segmentation. Previous studies indicate this approach can reduce toxicity and improve chemotherapy tolerance, which may improve outcomes and help optimized delivery of cytotoxic chemotherapy.

Conditions

Cervical Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IMRT with concurrent cisplatin 40 mg/m2

Intensity-modulated Radiation Therapy (IMRT) with concurrent cisplatin 40 mg/m2

Group Type: ACTIVE_COMPARATOR

Cisplatin

Intervention Type: DRUG

Weekly infusion of 40 mg/m2 (80 mg max) x 5 weeks

IMRT

Intervention Type: RADIATION

IMRT 45.0 Gy (intact) or 50.4 Gy (postoperative high-risk) in 1.8 Gy daily fractions over 5-5.5 weeks

PET-guided Bone Marrow-Sparing IMRT

PET-guided Bone Marrow-Sparing IMRT with concurrent cisplatin 40 mg/m2

Group Type: EXPERIMENTAL

PET-guided Bone Marrow-Sparing Intensity Modulated Radiation Therapy (IMRT)

Intervention Type: RADIATION

IMRT 45.0 Gy (intact) or 50.4 Gy (postoperative high-risk) in 1.8 Gy daily fractions over 5-5.5 weeks with PET-guided Bone Marrow-Sparing

Cisplatin

Intervention Type: DRUG

Weekly infusion of 40 mg/m2 (80 mg max) x 5 weeks

Interventions

PET-guided Bone Marrow-Sparing Intensity Modulated Radiation Therapy (IMRT)

IMRT 45.0 Gy (intact) or 50.4 Gy (postoperative high-risk) in 1.8 Gy daily fractions over 5-5.5 weeks with PET-guided Bone Marrow-Sparing

Intervention Type: RADIATION

Cisplatin

Weekly infusion of 40 mg/m2 (80 mg max) x 5 weeks

Intervention Type: DRUG

IMRT

IMRT 45.0 Gy (intact) or 50.4 Gy (postoperative high-risk) in 1.8 Gy daily fractions over 5-5.5 weeks

Intervention Type: RADIATION

Other Intervention Names

PET-guided Bone Marrow-Sparing IMRT; Platinol; Intensity Modulated Radiation Therapy

Eligibility Criteria

Inclusion Criteria

• Biopsy-proven, invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the cervix
• Biopsy result positive for carcinoma within 60 days prior to registration
• FIGO clinical stage I-IVA disease, based on standard diagnostic workup, including:History/physical examination and/or Examination under anesthesia (if indicated)
• If the patient is status post hysterectomy, one or more of the following conditions must be present: positive lymph nodes, positive margins, parametrial invasion, or non-radical surgery (i.e., simple hysterectomy).
• If the patient is inoperable, one or more of the following conditions must be present: clinical stage IB2-IVA, positive lymph nodes on nodal sampling or frozen section, and/or parametrial invasion
• Within 42 days prior to registration, the patient must have any of the following, if clinically indicated: examination under anesthesia, cystoscopy, sigmoidoscopy, rigid proctoscopy, or colonoscopy.
• X-ray (PA and lateral), CT scan, or PET/CT scan of the chest within 42 days prior to registration;
• CT scan, MRI, or PET/CT of the pelvis within 42 days prior to registration;
• Karnofsky Performance Status 60-100
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 10.0 g/dl is acceptable); Creatinine clearance ≥ 50 mg/dl; Bilirubin < 1.5 mg/dl; WBC ≥ 3,000/μl; ALT/AST < 3 x ULN; INR ≤ 1.5
• Negative serum pregnancy test for women of child-bearing potential

Exclusion Criteria

• Prior invasive malignancy (except non-melanomatous skin cancer), unless disease free for a minimum of 3 years;
• Prior systemic chemotherapy within the past three years
• Prior radiotherapy to the pelvis or abdomen that would result in overlap of radiation therapy fields;
• Para-aortic, inguinal, or gross (unresected) pelvic nodal metastasis. Gross pelvic nodal metastasis is defined as either: Radiographic evidence of nodal metastasis on CT or MRI (node having short axis diameter > 1 cm)OR Radiographic evidence of nodal metastasis on diagnostic FDG-PET or PET/CT scan (abnormally increased FDG uptake as determined and documented by the radiologist)OR Biopsy-proven metastasis (e.g. needle biopsy) in undissected node
• Distant metastasis
• Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
• Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• Uncontrolled diabetes, defined as diabetes mellitus, which in the opinion of any of the patient's physicians requires an immediate change in management;
• Uncompensated heart disease or uncontrolled high blood pressure
• Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Loren Mell, MD

Associate Professor, Director Division of Clinical and Translational Research, Department of Radiation Medicine and Applied Sciences.

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

University of Miami Miller School of Medicine

Miami, Florida, United States

Xijing Hospital

Xi'an, , China

University Hospital Hradec Králové

Hradec Králové, , Czechia

Tata Memorial Hospital

Pārel, Mumbai, India

Marie Sklodowska Cancer Center

Gliwice, , Poland

King Chulalongkorn Hospital

Bangkok, , Thailand

Countries

United States; China; Czechia; India; Poland; Thailand

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R21CA162718-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

INTERTECC

Identifier Type: -

Identifier Source: org_study_id