Radiation Therapy With or Without Chemotherapy in Patients With Stage I or Stage II Cervical Cancer Who Previously Underwent Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Gynecologic Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT01101451
First received: April 9, 2010
Last updated: August 8, 2014
Last verified: August 2014

April 9, 2010
August 8, 2014
April 2010
December 2020   (final data collection date for primary outcome measure)
RFS [ Time Frame: From protocol registration to date of first documented recurrence, death or date of last contact, assessed up to 11 years ] [ Designated as safety issue: No ]
Product-limit estimates according to the method of Kaplan and Meier and the one sided log-rank test (alpha=0.05) will be used to compare RFS between treatment arms.
Recurrence-free survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01101451 on ClinicalTrials.gov Archive Site
  • OS [ Time Frame: From entry into the study to death; or for living patients, the date of last contact regardless of whether or not this contact is on a subsequent protocol, assessed up to 11 years ] [ Designated as safety issue: No ]
    Product-limit estimates according to the method of Kaplan and Meier and the one sided log-rank test (alpha=0.05) will be used to compare OS between treatment arms.
  • Local control [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Assessed with Exact Logistic Regression adjusted known prognostic factors.
  • Site(s) of recurrence [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    The site(s) of first disease recurrence will be classified as: pelvic-only, extra-pelvic-only or pelvic-and-extra-pelvic and tabulated by treatment group. The test of the hypothesis that the probability of local failure is independent of randomized treatment will be assessed with exact logistic regression adjusted know prognostic factors.
  • Incidence of adverse events graded according to the active version of CTCAE [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    In addition to displaying frequency of adverse events for each grade category, significance of observed differences between treatment arms within each category will be analyzed using Fishers' exact test.
  • Patient risk-benefit [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
  • Treatment compliance [ Time Frame: Up to 11 years ] [ Designated as safety issue: No ]
    Assessed by the number of cycles and amount of chemoradiotherapy administered, treatment span, incidence and duration of treatment delays, reason for delays, and reason why off study therapy.
  • Quality of life, assessed using the FACT-Cx TOI, FACT-GOG/neurotoxicity 4 subscale, and the Brief Pain Inventory (BPI) [ Time Frame: Up to 9 months following the first day of treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Local control [ Designated as safety issue: No ]
  • Frequence and severity of adverse events as assessed by NCI CTCAE active version [ Designated as safety issue: Yes ]
  • Treatment compliance [ Designated as safety issue: No ]
  • Quality of life [ Designated as safety issue: No ]
  • Smoking history: prevalence of active smoking and extent of nicotine dependence [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Radiation Therapy With or Without Chemotherapy in Patients With Stage I or Stage II Cervical Cancer Who Previously Underwent Surgery
Randomized Phase III Clinical Trial of Adjuvant Radiation Versus Chemoradiation in Intermediate Risk, Stage I/IIA Cervical Cancer Treated With Initial Radical Hysterectomy and Pelvic Lymphadenectomy

This randomized phase III trial studies radiation therapy with chemotherapy to see how well it works compared to radiation therapy alone in treating patients with stage I or stage II cervical cancer who previously underwent surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving radiation therapy together with chemotherapy is more effective than radiation therapy alone in treating patients with cervical cancer.

PRIMARY OBJECTIVES:

I. To determine if post-operative adjuvant chemo-radiation therapy (CRT) can significantly improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in stage I-IIA cervical cancer patients with intermediate-risk factors after treatment with radical hysterectomy.

SECONDARY OBJECTIVES:

I. To determine whether post-operative adjuvant CRT can improve overall survival (OS) when compared to RT alone in stage I-IIA cervical cancer patients with intermediate risk factors after treatment with radical hysterectomy.

II. To assess differences (across treatment arms) in incidence and severity of therapy-attributed adverse events utilizing the active version of Common Terminology Criteria for Adverse Events (CTCAE).

III. To provide assessment of patient risk vs benefit (positive study only). IV. To determine whether post-operative adjuvant CRT improves the health-related quality-of-life (QOL) (compared to RT alone) as measured by Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) Trial Outcome Index (TOI) and produce favorable toxicity profiles (with particular focus on treatment related genitourinary, gastrointestinal, neurological, pain and sexual adverse events).

TERTIARY OBJECTIVES:

I. To bank archival tumor tissue for research studies, including studies that evaluate the association between biomarkers, RFS, OS, and clinical-surgical-pathologic characteristics in patients randomized to post-operative adjuvant CRT compared to RT alone.

II. To bank deoxyribonucleic acid (DNA) from whole blood for research studies, including studies that evaluate associations between single nucleotide polymorphisms (SNPs), and measures of clinical outcome, including RFS, OS, and adverse events in patients randomized to post-operative adjuvant CRT compared to RT alone.

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

ARM I: Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks.

ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Cell Carcinoma
  • Cervical Squamous Cell Carcinoma
  • Stage IA Cervical Cancer
  • Stage IB Cervical Cancer
  • Stage IIA Cervical Cancer
  • Drug: cisplatin
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Radiation: external beam radiation therapy
    Undergo radiotherapy
    Other Name: EBRT
  • Radiation: intensity-modulated radiation therapy
    Undergo radiotherapy
    Other Name: IMRT
  • Other: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Other: laboratory biomarker analysis
    Correlative studies
  • Active Comparator: Arm I (EBRT, IMRT)
    Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
    Interventions:
    • Radiation: external beam radiation therapy
    • Radiation: intensity-modulated radiation therapy
    • Other: quality-of-life assessment
    • Other: laboratory biomarker analysis
  • Experimental: Arm II (cisplatin, EBRT, IMRT)
    Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Drug: cisplatin
    • Radiation: external beam radiation therapy
    • Radiation: intensity-modulated radiation therapy
    • Other: quality-of-life assessment
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
534
Not Provided
December 2020   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Pathologically proven primary cervical cancer I-IIA with squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma initially treated with a standard radical hysterectomy with pelvic lymphadenectomy
  • Patients with the following characteristics (depth of stromal invasion and lymphovascular space involvement to be pathologically confirmed):

    • Positive capillary-lymphovascular space involvement and one of the following:

      • Deep third penetration
      • Middle third penetration, clinical tumor ≥ 2 cm
      • Superficial third penetration, clinical tumor ≥ 5 cm
    • Negative capillary-lymphatic space involvement

      • Middle or deep third penetration, clinical tumor ≥ 4 cm
  • Absolute neutrophil count (ANC) ≥ 1,500/mcl
  • Platelets ≥ 100,000/mcl
  • Creatinine ≤ upper limit of normal (ULN) or calculated creatinine clearance ≥ 60 mL/min
  • Bilirubin ≤ 1.5 times normal
  • Alkaline phosphate ≤ 3 times normal
  • Serum glutamic oxaloacetic transaminase (SGOT) ≤ 3 times normal
  • Gynecologic Oncology Group (GOG) performance status 0, 1, 2
  • Patients should not be randomized less than 3 weeks post-surgery but will not be acceptable for randomization more than 8 weeks post-surgery
  • Patients who have met the pre-entry requirements
  • Patients must have signed an approved informed consent and authorization permitting release of personal health information

Exclusion Criteria:

  • Patients with tumor in the parametria, pelvic lymph nodes or any other extra uterine site or with positive surgical margins
  • Patients with septicemia or severe infection
  • Patients with intestinal obstruction or gastrointestinal bleeding
  • Patients with postoperative fistula
  • Patients with cervix cancer who have received any previous radiation or chemotherapy
  • Patients whose circumstances do not permit completion of the study or the required follow-up
  • Patients with renal abnormalities requiring modification of radiation field (pelvic kidney, renal transplant, etc.)
  • Patients with GOG performance status of 3 or 4
  • 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 five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
Female
18 Years and older
No
United States,   Japan,   Korea, Republic of
 
NCT01101451
GOG-0263, NCI-2011-02037, GOG-0263, CDR0000670125, GOG-0263, GOG-0263, U10CA180868, U10CA027469
Yes
Gynecologic Oncology Group
Gynecologic Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Sang Ryu Gynecologic Oncology Group
Gynecologic Oncology Group
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP