Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer - Full Text View

Purpose

RATIONALE: Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. External radiation therapy uses high-energy x rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. It is not yet know whether giving cisplatin and external and internal radiation therapy together with carboplatin and paclitaxel kill more tumor cells.

PURPOSE: This randomized phase III trial studies how well giving cisplatin and radiation therapy together with or without carboplatin and paclitaxel works in treating patients with locally advanced cervical cancer.

Condition	Intervention	Phase
Cervical Cancer Chemotherapeutic Agent Toxicity Cognitive/Functional Effects Psychosocial Effects of Cancer and Its Treatment Radiation Toxicity Sexuality and Reproductive Issues	Drug: carboplatin Drug: cisplatin Drug: paclitaxel	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase III Trial of Adjuvant Chemotherapy Following Chemoradiation as Primary Treatment for Locally Advanced Cervical Cancer Compared to Chemoradiation Alone: The OUTBACK Trial

Resource links provided by NLM:

MedlinePlus related topics: Cancer Cervical Cancer

Drug Information available for: Cisplatin Paclitaxel Carboplatin

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Overall survival rate at 5 years [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival rate at 3 and 5 years [ Designated as safety issue: No ]
Rate of acute and long-term toxicities [ Designated as safety issue: Yes ]
Patterns of disease recurrence [ Designated as safety issue: No ]
Radiation protocol compliance [ Designated as safety issue: No ]
Quality of life including psychosexual health [ Designated as safety issue: No ]
Rate of complete and partial metabolic response on a PET scan performed 4 - 6 months after completion of chemoradiation treatment [ Designated as safety issue: No ]

Estimated Enrollment:	780
Study Start Date:	January 2012
Estimated Primary Completion Date:	July 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.	Drug: cisplatin Given IV
Experimental: Arm II Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV Drug: cisplatin Given IV Drug: paclitaxel Given IV

Detailed Description:

OBJECTIVES:

Primary

To determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves overall survival.

Secondary

To determine the progression-free survival rates.
To determine acute and long-term toxicities.
To determine patterns of disease recurrence.
To determine the association between radiation protocol compliance and outcomes.
To determine patient quality of life, including psycho-sexual health.

Tertiary

To determine the association between the results of a follow-up PET scan performed 4 - 6 months post completion of chemoradiation and outcomes for all patients in the trial.
To determine the biological predictors of patients' outcomes based on translational laboratory studies of blood and tissue specimens.

OUTLINE: This is a multicenter study. Patients are stratified according to pelvic or common iliac nodal involvement (yes vs no), requirement for extended-field radiotherapy treatment (yes vs no), FIGO stage (IB/IIA vs IIB vs IIIB/IVA), age (< 60 years of age vs ≥ 60 years of age), and hospital/site. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive cisplatin IV over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.
Arm II: Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo baseline tumor biopsy and blood collection for future correlative studies.

Patients complete the European Organization for Research and Treatment of Cancer (EORTC) Core questionnaire (QLQ-C30), the EORTC cervix cancer module (CX24), the ovarian cancer module (OV28), and the Sexual function-Vaginal Changes Questionnaire (SVQ) questionnaires at baseline, during, and after completion of study treatment.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:
- Histological diagnosis of squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix
- FIGO 2008 stage IB1 & node positive, IB2, II, IIIB, or IVA disease
No patients assessed at presentation as requiring interstitial brachytherapy treatment
No para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven, PET positive, or ≥ 15 mm short-axis diameter on CT)
No evidence of distant metastases

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
WBC ≥ 3,000/mm³
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
AST/ALT ≤ 2.5 times ULN
Creatinine ≤ ULN (CTC Grade 0) OR calculated creatinine clearance ≥ 60 mL/min OR ≥ 50 mL/min by EDTA creatinine clearance
No patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfils the required inclusion criteria
No prior diagnosis of Crohn disease or ulcerative colitis
No peripheral neuropathy ≥ grade 2 (per CTCAE v. 4)
No patients with other invasive malignancies, with the exception of non-melanoma skin cancer and in situ melanoma, who had (or have) any evidence of the other cancer present within the last 5 years
No patients who are pregnant or lactating
No serious illness or medical condition that precludes the safe administration of the trial treatment including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Not HIV positive

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior pelvic radiotherapy
No prior chemotherapy for this tumor
No patients who have undergone prior hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy
No patients with any contraindication to cisplatin, carboplatin, or paclitaxel chemotherapy
No concurrent intensity-modulated radiation therapy or interstitial brachytherapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01414608

Show 71 Study Locations

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Kathleen N. Moore, MD

Oklahoma University Cancer Institute

More Information

No publications provided

Responsible Party:	Philip J. DiSaia, Gynecologic Oncology Group
ClinicalTrials.gov Identifier:	NCT01414608 History of Changes
Other Study ID Numbers:	CDR0000706698, ANZGOG-0902-GOG-0274/RTOG-1174
Study First Received:	August 10, 2011
Last Updated:	October 27, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage IB cervical cancer
stage IIA cervical cancer
stage IIB cervical cancer
stage III cervical cancer
stage IVA cervical cancer
sexuality and reproductive issues
radiation toxicity

chemotherapeutic agent toxicity
psychosocial effects of cancer and its treatment
cognitive/functional effects
cervical adenocarcinoma
cervical adenosquamous cell carcinoma
cervical squamous cell carcinoma

Additional relevant MeSH terms:

Uterine Cervical Neoplasms
Radiation Injuries
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Wounds and Injuries
Cisplatin

Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 21, 2013