Trial record 1 of 1 for:    GOG 0249
Previous Study | Return to List | Next Study

Pelvic Radiation Therapy or Vaginal Implant Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Stage I or Stage II Endometrial Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00807768
First received: December 11, 2008
Last updated: March 17, 2016
Last verified: March 2016
  Purpose
This randomized phase III trial studies pelvic radiation therapy to see how well it works compared with vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer. Radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether pelvic radiation therapy alone is more effective than vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with endometrial cancer.

Condition Intervention Phase
Endometrial Clear Cell Adenocarcinoma
Endometrial Serous Adenocarcinoma
Fatigue
Neurotoxicity Syndrome
Obesity
Stage I Uterine Corpus Cancer
Stage II Uterine Corpus Cancer
Radiation: 3-Dimensional Conformal Radiation Therapy
Drug: Carboplatin
Radiation: Intensity-Modulated Radiation Therapy
Radiation: Internal Radiation Therapy
Other: Laboratory Biomarker Analysis
Drug: Paclitaxel
Other: Quality-of-Life Assessment
Other: Questionnaire Administration
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients With High Risk, Early Stage Endometrial Carcinoma

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Primary Outcome Measures:
  • Duration of recurrence-free survival [ Time Frame: From study entry until disease recurrence, death, or date of last contact, assessed up to 10 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Contributing cause of death [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The cumulative incidence will be estimated using methods that account for competing risks.

  • Cumulative incidence of extra-pelvic recurrence [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The cumulative incidence will be estimated using methods that account for competing risks.

  • Cumulative incidence of pelvic/vaginal recurrence [ Time Frame: Up to 10 years ] [ Designated as safety issue: No ]
    The cumulative incidence will be estimated using methods that account for competing risks.

  • Duration of overall survival [ Time Frame: From entry into the study to death or the date of last contact, assessed up to 10 years ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Frequency and severity of acute and late adverse effects assessed by Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 10 years ] [ Designated as safety issue: Yes ]
    The maximum grade over the entire course of therapy for any individual effect will be used as a summary of acute toxicity. The Kruskal-Wallis test corrected for ties will be used to compare the maximum grade of acute adverse effects of therapy by treatment regimen. The maximum grade over the follow-up period (prior to initiation of subsequent therapy) for any individual effect will be used as summary of late adverse effects. The cumulative incidence of grade 3 or higher bowel-related gastrointestinal adverse events will also be estimated using the date of onset accounting for competing events.

  • Gene expression based risk score [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Patient-reported quality of life as assessed by questionnaires [ Time Frame: Up to 14 months post-treatment ] [ Designated as safety issue: No ]
    Assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) Physical Well-being (PWB) and Functional Well-being (FWB) subscales (14 items), FACT-English (En) additional concerns subscale (16 items), FACT/GOG-neurotoxicity (NTX)-4 subscale (4 items), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue (13 items), items Cx4, C3 and C5 from FACT-Cervix (Cx) and PROMIS Fatigue Short Form 1 (7 items).


Enrollment: 555
Study Start Date: March 2009
Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I (pelvic radiation therapy)
Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
Radiation: 3-Dimensional Conformal Radiation Therapy
Undergo pelvic radiation therapy
Other Names:
  • 3-dimensional radiation therapy
  • 3D CONFORMAL RADIATION THERAPY
  • 3D CRT
  • 3D-CRT
  • Conformal Therapy
  • Radiation Conformal Therapy
Radiation: Intensity-Modulated Radiation Therapy
Undergo pelvic radiation therapy
Other Names:
  • IMRT
  • Intensity Modulated RT
  • Intensity-Modulated Radiotherapy
Radiation: Internal Radiation Therapy
Undergo vaginal cuff brachytherapy
Other Names:
  • BRACHYTHERAPY
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies
Experimental: Arm II (brachytherapy, paclitaxel, carboplatin)
Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.
Drug: Carboplatin
Given IV
Other Names:
  • Blastocarb
  • Carboplat
  • Carboplatin Hexal
  • Carboplatino
  • Carbosin
  • Carbosol
  • Carbotec
  • CBDCA
  • Displata
  • Ercar
  • JM-8
  • Nealorin
  • Novoplatinum
  • Paraplat
  • Paraplatin
  • Paraplatin AQ
  • Paraplatine
  • Platinwas
  • Ribocarbo
Radiation: Internal Radiation Therapy
Undergo vaginal cuff brachytherapy
Other Names:
  • BRACHYTHERAPY
  • Internal Radiation
  • Internal Radiation Brachytherapy
  • Radiation Brachytherapy
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat
Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment
Other: Questionnaire Administration
Ancillary studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if treatment with vaginal cuff brachytherapy followed by three cycles of chemotherapy reduces the rate of recurrence or death (i.e. increases recurrence-free survival) when compared to pelvic radiation therapy.

SECONDARY OBJECTIVES:

I. To compare survival between the two treatment groups. II. To compare patterns of failure between the two treatment groups. III. To compare physical functioning, fatigue and neurotoxicity between the two treatment groups.

IV. To examine associations between primary comorbid illnesses and obesity on survival, fatigue and physical functioning.

V. To evaluate the psychometric properties (such as construct validity, reliability, sensitivity to treatment and responsiveness over time) of the Patient-Reported-Outcomes Measurement Information System (PROMIS) Fatigue Short form 1, and to evaluate fatigue measurement equivalence between women with endometrial cancer and age-matched women from the general United States (US) population.

TERTIARY OBJECTIVES:

I. To evaluate the ability of gene expression signatures in early stage endometrial cancer to predict recurrence and to explore the association between gene expression signatures in early stage endometrial cancer and clinical characteristics and outcome.

II. To bank whole blood specimens for future research.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients undergo conventional or intensity-modulated pelvic radiation therapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.

ARM II: Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel intravenously (IV) over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • To be considered eligible to participate in this trial, all patients must have undergone hysterectomy; bilateral salpingo-oophorectomy (open or laparoscopic approach) is strongly encouraged
  • Peritoneal cytology should be obtained on entering the peritoneal cavity, as described in the Gynecologic Oncology Group (GOG) Surgical Procedures Manual (https://gogmember.gog.org/manuals/pdf/surgman.pdf); pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged (as staged patients enrolled on GOG-0210-molecular markers in endometrial carcinoma are eligible for this study)

    • The procedures may be performed via laparotomy or laparoscopy (including robot-assisted) as per the surgeon's preference; the surgeon must record in the operative report whether a lymphadenectomy was performed (see link above to Surgical Procedures Manual) or not; a specific number of lymph nodes removed will not be utilized for eligibility, but the operative report should reflect that the procedure performed was consistent with the procedures described in the GOG Surgical Manual
  • If either a bilateral salpingo-oophorectomy or nodal dissection was not performed, post-operative pre-treatment computed tomography (CT)/magnetic resonance imaging (MRI) is required and must not demonstrate evidence suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease); post-operative, pre-treatment CT/MRI must be performed if a pelvic and para-aortic nodal dissection was not performed
  • For the purposes of description, patients will be staged according to the International Federation of Gynecology and Obstetrics (FIGO) 2009 staging system; eligibility is defined based on clinical-pathologic features; patients with endometrial carcinoma (endometrioid types) confined to the corpus uteri or with endocervical glandular involvement fitting one of the following high-intermediate risk factor categories:

    • Age >= 70 years with one risk factor
    • Age >= 50 with 2 risk factors
    • Age >= 18 years with 3 risk factors
    • Risk factors: grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ½ myometrial invasion; patients with these risk criteria may be enrolled with either positive or negative cytology
  • Patients with stage II endometrial carcinoma (any histology) with cervical stromal invasion (occult or gross involvement), with or without high-intermediate risk factors
  • Patients with serous or clear cell histology (with or without other high-intermediate risk factors) are eligible provided the disease is uterine-confined (with or without cervical stromal invasion or endocervical glandular involvement), and with peritoneal cytology negative for malignancy
  • Patients must have GOG performance status 0, 1, or 2
  • Absolute neutrophil count (ANC) >= 1,500/mcl (equivalent to Common Toxicity Criteria [CTCAE version [v] 3.0] grade 1)
  • Platelets >= 100,000/mcl (CTCAE v3.0 grade 0-1)
  • Serum creatinine =< institutional upper limit normal (ULN), CTCAE v 3.0 grade 0

    • Note: If serum creatinine > ULN, a 24-hour creatinine clearance must be collected and must be > 50 mL/min
  • Bilirubin =< 1.5 x ULN (CTCAE v3.0 grade 1)
  • Serum glutamic oxaloacetic transaminase (SGOT) =< 2.5 x ULN (CTCAE grade 0-1)
  • Alkaline phosphatase =< 2.5 x ULN (CTCAE grade 0-1)
  • Neuropathy (sensory and motor) =< CTCAE v3.0 grade 1
  • Patients who have met the pre-entry requirements; testing values/results must meet eligibility criteria
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Patients who have already received non-surgical therapy for endometrial cancer including chemotherapy, radiation (example, pre-operative or post-operative brachytherapy), hormonal or biologic therapy
  • Patients identified with pathologically confirmed spread of cancer beyond the uterus and cervix to pelvic or para-aortic lymph nodes, adnexal structures, and/or other anatomic sites, or patients with serous or clear cell histology and with positive cytologic washings
  • Patients with nodal (for patients who did not have nodal dissection performed) or distant disease determined based on imaging studies; patients with suspicious nodes that have been biopsied (re-staging operation, fine needle aspiration [FNA]) and are pathologically negative will be eligible
  • Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 5 years; patients are excluded if their previous cancer treatment contraindicates this protocol therapy; specifically, patients who have received prior radiotherapy directed to treat disease within the abdominal cavity or pelvis are excluded
  • Prior radiation of localized cancer of the breast, head and neck, thyroid, or skin is permitted, provided that it was completed more than 5 years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than 5 years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have contraindications to pelvic radiation therapy (RT) (e.g. pelvic kidney, connective tissue disease, inflammatory bowel disease, etc.) should be screened in advance and not be considered eligible for the trial
  • Patients with recurrent endometrial cancer
  • Patients with surgical or clinical, FIGO 2009 stage III or IV endometrial carcinoma
  • Patients with non-epithelial uterine malignancies such as uterine carcinosarcoma or leiomyosarcoma
  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: NCT00807768

  Show 525 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
National Cancer Institute (NCI)
Investigators
Principal Investigator: Marcus Randall NRG Oncology
  More Information

Responsible Party: Gynecologic Oncology Group
ClinicalTrials.gov Identifier: NCT00807768     History of Changes
Other Study ID Numbers: GOG-0249  NCI-2009-00610  CDR0000629591  GOG-0249  GOG-0249  U10CA180868  U10CA027469 
Study First Received: December 11, 2008
Last Updated: March 17, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Adenocarcinoma
Fatigue
Uterine Neoplasms
Neurotoxicity Syndromes
Cystadenocarcinoma, Serous
Adenocarcinoma, Clear Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Signs and Symptoms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Uterine Diseases
Genital Diseases, Female
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Cystadenocarcinoma
Neoplasms, Cystic, Mucinous, and Serous
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 24, 2016