Cervical Cancer
Conditions
Keywords
cervical adenocarcinoma, cervical adenosquamous cell carcinoma, cervical squamous cell carcinoma, stage IA cervical cancer, stage IB cervical cancer, stage IIA cervical cancer
Brief summary
RATIONALE: Drugs used in chemotherapy, such as cisplatin, paclitaxel, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. It is not yet known whether chemotherapy and radiation therapy are more effective when given with or without additional chemotherapy in treating cervical cancer. PURPOSE: This randomized phase III trial is studying chemotherapy and pelvic radiation therapy to see how well they work when given with or without additional chemotherapy in treating patients with high-risk early-stage cervical cancer after radical hysterectomy.
Detailed description
OBJECTIVES: Primary * To determine if administering adjuvant systemic chemotherapy after chemoradiotherapy will improve disease-free survival compared to chemoradiotherapy alone in patients with high-risk early-stage cervical carcinoma found to have positive nodes and/or positive parametria after radical hysterectomy. Secondary * To evaluate adverse events. * To evaluate overall survival. * To evaluate quality of life. * To evaluate chemotherapy-induced neuropathy. * To perform a post-hoc dose-volume evaluation between patients treated with standard radiotherapy and patients treated with intensity-modulated radiotherapy (IMRT) with respect to toxicity and local control. * To collect fixed tissue samples to identify tumor molecular signatures that may be associated with patient outcomes, such as adverse events, disease-free survival, and overall survival. * To collect blood samples to identify secreted factors from serum and plasma that may be associated with adverse events or outcome and to identify single nucleotide polymorphisms (SNPs) in genes from buffy coat that may be associated with a genetic predisposition to tumor formation itself or a response to cytotoxic therapy. OUTLINE: This is a multicenter study. Patients are stratified according to planned use of brachytherapy (no vs. yes), radiotherapy modality - \[standard external beam radiotherapy (EBRT) vs. intensity-modulated radiotherapy (IMRT)\], and radiotherapy dose (45 Gy vs. 50.4 Gy). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients undergo standard EBRT or IMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin IV over 1 hour once weekly for 6 weeks. NOTE: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy. * Arm II: Patients receive chemoradiotherapy as in arm I. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed by the Functional Assessment of Cancer Therapy - Gynecologic Oncology Group (FACT-GOG/NTX4), FACT-Cx, and FACIT-D questionnaires at baseline; at the completion of chemoradiotherapy; and then at 6, 12, and 24 months after completion of chemoradiotherapy. Blood and tissue samples may be collected for gene expression analysis by immuno-histochemistry (IHC) and for biomarker and polymorphism studies. After completion of study treatment, patients are followed up very 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Interventions
DRUGcarboplatin
Intravenously
DRUGcisplatin
Intravenously
DRUGpaclitaxel
Intravenously
RADIATIONintensity-modulated radiation therapy
Daily fractions
Daily fractions
RADIATIONOptional brachytherapy boost
Low-dose rate (20-25 Gy single application) or high-dose rate (12-18 Gy 2-3 applications), dependent on external beam dose.
Sponsors
National Cancer Institute (NCI)
NRG Oncology
Radiation Therapy Oncology Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed squamous, adenosquamous, or adenocarcinoma of the cervix with any/all of the following high-risk features after surgery: * Positive pelvic nodes * Positive parametrium * Positive para-aortic nodes that have been completely resected and are positron emission tomography (PET)/computed tomography (CT) scan-negative * PET only required if positive para-aortic nodes during surgery * Clinical stage IA2, IB, or IIA disease (this corresponds to surgical tumor node metastasis (TNM) staging of T1-T2, N1, M0) * Must have undergone radical hysterectomy (open, laparoscopically, or robotic) and staging within the past 70 days * Para-aortic and pelvic node sampling required * If the patient did not have a para-aortic lymph node sampling/dissection, but had common iliac node dissection that was negative, a PET-CT is recommended, but not required * A negative pre- or post-operative PET scan or PET-CT scan of the para-aortic nodes is required if the patient did not undergo para-aortic or common iliac nodal sampling/dissection * No gross residual disease * No neuroendocrine histology * No distant metastases PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * Absolute neutrophil count (ANC) ≥ 1,800/mm³ * Platelets ≥ 100,000/mm³ * White blood cell count (WBC) ≥ 4,000/mm³ * Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention allowed) * Serum creatinine ≤ 1.5 mg/dL * Bilirubin ≤ 1.5 times upper limit of normal * Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) normal * Alkaline phosphatase normal * Known HIV positivity allowed provided cluster of differentiation 4 (CD4) count is ≥ 350/mm³ within the past 14 days * No other invasive malignancy within the past 3 years, except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix * No severe, active co-morbidity, including any of the following: * Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months * Transmural myocardial infarction within the past 6 months * Acute bacterial or fungal infection requiring IV antibiotics at the time of study entry * Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study entry * Coagulation defects * No prior allergic reaction to carboplatin, paclitaxel, and/or cisplatin PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior systemic chemotherapy for the current cervical cancer * Prior chemotherapy for a different cancer is allowed * No prior radiotherapy to the pelvis that would result in overlap of radiotherapy fields
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (Percentage of Participants Alive Without Disease) | From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported. | Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (Percentage of Participants Alive) | From randomization to death or last follow-up. Maximum follow-up time at time of analysis was 12.8 years. The 2- and 4-year survival estimates are reported. | Overall survival is estimated by the Kaplan-Meier method. The distribution of survival estimates between the two arms is compared using the log rank test. Survival time is measured from the date of randomization to the date of death from any cause or last known follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants. |
| Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) at 12 Months | Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks) | The FACT-GOG/NTX4 measures patient-reported symptoms of chemotherapy-induced peripheral neuropathy in cancer patients. Possible scores range from 0 to 16 with higher scores indicating a better condition. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms. |
| Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Diarrhea Subscore at 12 Months | Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks) | The diarrhea-specific subscore of the FACIT-D measures patient-reported diarrhea symptoms. Possible scores range from 0 to 44 with higher scores indicating a better quality of life. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms. |
| Functional Assessment of Cancer Therapy - Cervix (FACT-Cx) Cervical Cancer Subscore at 12 Months | Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks) | The cervical cancer subscore of the FACT-Cx measures patient-reported symptoms and problems related to cervical cancer. Possible scores range from 0 to 60 with higher scores indicating a better quality of life. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms. |
| Associations Between Secreted Factors From Serum and Plasma With Adverse Events or Outcome | From randomization to last follow-up. | — |
| Associations Between Single Nucleotide Polymorphisms (SNPs) in Genes From Buffy Coat and a Genetic Predisposition to Tumor Formation Itself or a Response to Cytotoxic Therapy | From randomization to last follow-up. | — |
| Number of Participants by Highest Grade Adverse Event Reported | From randomization to the date of last known follow-up. Maximum follow-up time was 12.8 years. | Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. |
| Associations Between Tumor Molecular Signatures, From Fixed Tissue, and Outcomes Such as Adverse Events, Disease Free Survival and Overall Survival | From randomization to last follow-up | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported. | NIH-required analysis. Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants. |
| Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported. | NIH-required analysis. Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants. |
Countries
Canada, Hong Kong, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I: Cisplatin/Radiation Therapy Standard external beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) to the pelvis once daily 5 days a week for 5-6 weeks as 45 Gy in 25 fractions or 50.4 Gy in 28 fractions (1.8 Gy/fraction). Concurrent cisplatin IV over one hour once weekly for 6 weeks as 40 mg/m\^2, maximum dose 70 mg. A brachytherapy boost following radiation therapy is optional. | 109 |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel Chemoradiotherapy as in arm I, followed 4-6 weeks later by paclitaxel IV \[135 mg/m2, with maximum body surface area (BSA) of 2.0 m\^2 over 3 hours\] and carboplatin IV \[area under the curve (AUC) 5 over 30 minutes\] on day 1 of 21-day cycle for 4 cycles in the absence of disease progression or unacceptable toxicity. | 103 |
| Total | 212 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 9 | 15 |
Baseline characteristics
| Characteristic | Arm I: Cisplatin/Radiation Therapy | Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Total |
|---|---|---|---|
| Age, Customized | 47 years | 45 years | 46 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 95 Participants | 92 Participants | 187 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| FIGO Staging (clinical) [AJCC 6th Edition] IA2 | 3 Participants | 6 Participants | 9 Participants |
| FIGO Staging (clinical) [AJCC 6th Edition] IB | 97 Participants | 88 Participants | 185 Participants |
| FIGO Staging (clinical) [AJCC 6th Edition] IIA | 9 Participants | 9 Participants | 18 Participants |
| Histologic grade G1-Well differentiated | 10 Participants | 5 Participants | 15 Participants |
| Histologic grade G2-Moderately differentiated | 58 Participants | 52 Participants | 110 Participants |
| Histologic grade G3-Poorly differentiated | 27 Participants | 31 Participants | 58 Participants |
| Histologic grade Gx-Grade cannot be assessed | 14 Participants | 15 Participants | 29 Participants |
| Histologic Type Adenocarcinoma, not otherwise specificed (NOS) | 15 Participants | 24 Participants | 39 Participants |
| Histologic Type Adenosquamous carcinoma | 6 Participants | 5 Participants | 11 Participants |
| Histologic Type Squamous cell carcinoma | 88 Participants | 74 Participants | 162 Participants |
| Hysterectomy Procedure Laparoscopic | 26 Participants | 22 Participants | 48 Participants |
| Hysterectomy Procedure Open | 64 Participants | 54 Participants | 118 Participants |
| Hysterectomy Procedure Robotic | 19 Participants | 27 Participants | 46 Participants |
| Intended RT Dose 45 Gy | 35 Participants | 30 Participants | 65 Participants |
| Intended RT Dose 50.4 Gy | 74 Participants | 73 Participants | 147 Participants |
| Intended RT Modality IMRT | 63 Participants | 62 Participants | 125 Participants |
| Intended RT Modality Standard RT | 46 Participants | 41 Participants | 87 Participants |
| Intention to use brachytherapy No | 61 Participants | 58 Participants | 119 Participants |
| Intention to use brachytherapy Yes | 48 Participants | 45 Participants | 93 Participants |
| Pathologic M-Stage M0 | 108 Participants | 103 Participants | 211 Participants |
| Pathologic M-Stage M1 | 1 Participants | 0 Participants | 1 Participants |
| Pathologic N-Stage N0 | 30 Participants | 26 Participants | 56 Participants |
| Pathologic N-Stage N1 | 79 Participants | 77 Participants | 156 Participants |
| Pathologic T-Stage T0 | 2 Participants | 1 Participants | 3 Participants |
| Pathologic T-Stage T1 | 1 Participants | 2 Participants | 3 Participants |
| Pathologic T-Stage T1a1 | 1 Participants | 1 Participants | 2 Participants |
| Pathologic T-Stage T1a2 | 2 Participants | 6 Participants | 8 Participants |
| Pathologic T-Stage T1b | 4 Participants | 8 Participants | 12 Participants |
| Pathologic T-Stage T1b1 | 39 Participants | 34 Participants | 73 Participants |
| Pathologic T-Stage T1b2 | 23 Participants | 15 Participants | 38 Participants |
| Pathologic T-Stage T2 | 6 Participants | 10 Participants | 16 Participants |
| Pathologic T-Stage T2b | 30 Participants | 24 Participants | 54 Participants |
| Pathologic T-Stage T3b | 1 Participants | 2 Participants | 3 Participants |
| Positive Para-Aortic Nodes No | 54 Participants | 43 Participants | 97 Participants |
| Positive Para-Aortic Nodes Not sampled / dissected | 52 Participants | 55 Participants | 107 Participants |
| Positive Para-Aortic Nodes Yes | 3 Participants | 5 Participants | 8 Participants |
| Positive Parametrium No | 53 Participants | 58 Participants | 111 Participants |
| Positive Parametrium Yes | 56 Participants | 45 Participants | 101 Participants |
| Positive Pelvic Nodes No | 33 Participants | 23 Participants | 56 Participants |
| Positive Pelvic Nodes Yes | 76 Participants | 80 Participants | 156 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 42 Participants | 40 Participants | 82 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 9 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) White | 60 Participants | 49 Participants | 109 Participants |
| Sex: Female, Male Female | 109 Participants | 103 Participants | 212 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Zubrod performance status 0 | 87 Participants | 79 Participants | 166 Participants |
| Zubrod performance status 1 | 22 Participants | 24 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 17 / 109 | 13 / 103 |
| other Total, other adverse events | 103 / 107 | 99 / 101 |
| serious Total, serious adverse events | 14 / 107 | 25 / 101 |
Outcome results
Primary
Disease-free Survival (Percentage of Participants Alive Without Disease)
Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.
Time frame: From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.
Population: Eligible participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) | 2 years | 86.4 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) | 4 years | 76.2 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) | 2 years | 82.1 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) | 4 years | 76.9 percentage of participants |
Comparison: Sample size calculations are based on the primary hypothesis that 4 additional cycles of carboplatin and paclitaxel following concurrent radiation and weekly cisplatin will increase 4-year DFS from 80% to 90% for patients with cervical carcinoma with positive nodes and/or positive margins after a radical hysterectomy. One-sided alpha=0.05, statistical power=80%, 5.5 years of accrual with 4 years of follow-up, 2 interim significance tests. 50 DFS events are required to trigger this analysis.p-value: 0.5690% CI: [0.65, 1.68]Log Rank
Secondary
Associations Between Secreted Factors From Serum and Plasma With Adverse Events or Outcome
Time frame: From randomization to last follow-up.
Population: The protocol did not provide sufficient detail to meet current National Cancer Institute requirements for release of specimens from the NRG Oncology tissue bank for the protocol-specified objective, therefore no assays were performed, and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.
Secondary
Associations Between Single Nucleotide Polymorphisms (SNPs) in Genes From Buffy Coat and a Genetic Predisposition to Tumor Formation Itself or a Response to Cytotoxic Therapy
Time frame: From randomization to last follow-up.
Population: The protocol did not provide sufficient detail to meet current National Cancer Institute requirements for release of specimens from the NRG Oncology tissue bank for the protocol-specified objective, therefore no assays were performed, and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.
Secondary
Associations Between Tumor Molecular Signatures, From Fixed Tissue, and Outcomes Such as Adverse Events, Disease Free Survival and Overall Survival
Time frame: From randomization to last follow-up
Population: The protocol did not provide sufficient detail to meet current National Cancer Institute requirements for release of specimens from the NRG Oncology tissue bank for the protocol-specified objective, therefore no assays were performed, and no data were collected for this outcome measure. Specimen use will require federal approval and funding separate from this trial.
Secondary
Functional Assessment of Cancer Therapy - Cervix (FACT-Cx) Cervical Cancer Subscore at 12 Months
The cervical cancer subscore of the FACT-Cx measures patient-reported symptoms and problems related to cervical cancer. Possible scores range from 0 to 60 with higher scores indicating a better quality of life. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms.
Time frame: Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
Secondary
Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) at 12 Months
The FACT-GOG/NTX4 measures patient-reported symptoms of chemotherapy-induced peripheral neuropathy in cancer patients. Possible scores range from 0 to 16 with higher scores indicating a better condition. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms.
Time frame: Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
Secondary
Functional Assessment of Chronic Illness Therapy - Diarrhea (FACIT-D) Diarrhea Subscore at 12 Months
The diarrhea-specific subscore of the FACIT-D measures patient-reported diarrhea symptoms. Possible scores range from 0 to 44 with higher scores indicating a better quality of life. Analysis of covariance, using the baseline score as a covariate, will be used to determine if there is a difference between the treatment arms.
Time frame: Baseline and 12 months after the completion of concurrent chemoradiation (6 weeks)
Secondary
Number of Participants by Highest Grade Adverse Event Reported
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity as follows: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, 5 = death related to adverse event. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data.
Time frame: From randomization to the date of last known follow-up. Maximum follow-up time was 12.8 years.
Population: Eligible participants who started protocol treatment and were assessed for adverse events.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I: Cisplatin/Radiation Therapy | Number of Participants by Highest Grade Adverse Event Reported | Grade 4 | 8 Participants |
| Arm I: Cisplatin/Radiation Therapy | Number of Participants by Highest Grade Adverse Event Reported | Grade 1 | 13 Participants |
| Arm I: Cisplatin/Radiation Therapy | Number of Participants by Highest Grade Adverse Event Reported | Grade 2 | 43 Participants |
| Arm I: Cisplatin/Radiation Therapy | Number of Participants by Highest Grade Adverse Event Reported | Grade 3 | 39 Participants |
| Arm I: Cisplatin/Radiation Therapy | Number of Participants by Highest Grade Adverse Event Reported | Grade 5 | 0 Participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Number of Participants by Highest Grade Adverse Event Reported | Grade 5 | 0 Participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Number of Participants by Highest Grade Adverse Event Reported | Grade 3 | 44 Participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Number of Participants by Highest Grade Adverse Event Reported | Grade 1 | 4 Participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Number of Participants by Highest Grade Adverse Event Reported | Grade 4 | 21 Participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Number of Participants by Highest Grade Adverse Event Reported | Grade 2 | 30 Participants |
Secondary
Overall Survival (Percentage of Participants Alive)
Overall survival is estimated by the Kaplan-Meier method. The distribution of survival estimates between the two arms is compared using the log rank test. Survival time is measured from the date of randomization to the date of death from any cause or last known follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.
Time frame: From randomization to death or last follow-up. Maximum follow-up time at time of analysis was 12.8 years. The 2- and 4-year survival estimates are reported.
Population: Eligible participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Cisplatin/Radiation Therapy | Overall Survival (Percentage of Participants Alive) | 2 years | 91.9 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Overall Survival (Percentage of Participants Alive) | 4 years | 87.3 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Overall Survival (Percentage of Participants Alive) | 2 years | 91.4 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Overall Survival (Percentage of Participants Alive) | 4 years | 89.0 percentage of participants |
Comparison: The 4-year overall survival rate for the control arm is expected to be approximately 85%. The overall survival will be compared between the two arms. The final targeted sample size of 235 patients with the longer accrual time, will provide 64% and 78% power to detect an increase in overall survival to 92% and 93% respectively, with a 1- sided alpha of 0.05.p-value: 0.490% CI: [0.49, 1.69]Log Rank
Other Pre-specified
Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity
NIH-required analysis. Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.
Time frame: From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.
Population: Eligible participants stratified by ethnicity
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Hispanic or Latino: 2 years | 83.9 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Hispanic or Latino: 4 years | 83.9 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Not Hispanic or Latino: 2 years | 86.7 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Not Hispanic or Latino: 4 years | 75.4 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Unknown or Not Reported: 2 years | NA percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Unknown or Not Reported: 4 years | NA percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Unknown or Not Reported: 2 years | 0 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Hispanic or Latino: 2 years | 77.8 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Not Hispanic or Latino: 4 years | 79.0 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Hispanic or Latino: 4 years | 64.8 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Unknown or Not Reported: 4 years | 0 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Ethnicity | Not Hispanic or Latino: 2 years | 83.4 percentage of participants |
Other Pre-specified
Disease-free Survival (Percentage of Participants Alive Without Disease) by Race
NIH-required analysis. Disease-free survival (DFS) is estimated by the Kaplan-Meier method. The distribution of DFS estimates between the two arms is compared using the log rank test. DFS time is measured from the date of randomization to the date of first DFS failure (local, regional or distant metastases failure or death due to any cause) or last follow-up (censored). Analysis was to occur after disease or death was reported for 50 participants.
Time frame: From randomization to first failure (local, regional, or distant metastases failure or death due to any cause) or last follow-up. Maximum follow-up at the time of analysis was 12.8 years. The 2- and 4-year DFS estimates are reported.
Population: Eligible participants stratified by race
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | White: 2 years | 85.9 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Asian: 2 years | 87.1 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | White: 4 years | 75.4 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Black or African American: 2 years | 100 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | More than one race: 2 years | 100 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | More than one race: 4 years | NA percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Unknown or Not Reported: 2 years | 0 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | American Indian or Alaska Native: 4 years | NA percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Unknown or Not Reported: 4 years | 0 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | American Indian or Alaska Native: 2 years | 100 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Black or African American: 4 years | 100 percentage of participants |
| Arm I: Cisplatin/Radiation Therapy | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Asian: 4 years | 76.0 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Unknown or Not Reported: 4 years | 50 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | American Indian or Alaska Native: 2 years | 100 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | American Indian or Alaska Native: 4 years | NA percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Asian: 2 years | 74.4 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Asian: 4 years | 64.2 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Black or African American: 2 years | 87.5 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Black or African American: 4 years | 87.5 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | White: 2 years | 89.3 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | White: 4 years | 86.6 percentage of participants |
| Arm II: Cisplatin/Radiation Therapy + Carboplatin/Paclitaxel | Disease-free Survival (Percentage of Participants Alive Without Disease) by Race | Unknown or Not Reported: 2 years | 50 percentage of participants |