Trial Outcomes & Findings for Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer (NCT NCT01414608)

Last Updated: 2022-11-07

Results Overview

Estimate for probability of overall survival at 5 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

926 participants

Primary outcome timeframe

5 years from study randomization

Results posted on

2022-11-07

Participant Flow

Study was open to accrual on January 9th 2012. Accrual ended on June 28th 2017

Participant milestones

Participant milestones
Measure	Standard Chemoradiation Standard Chemoradiation (CRT)	Standard Chemoradiation With Adjuvant Chemotherapy Standard Chemoradiation (CRT) followed by 4 cycles of carboplatin and paclitaxel (Adjuvant)
Overall Study STARTED	461	465
Overall Study COMPLETED	456	463
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Chemoradiation Standard Chemoradiation (CRT)	Standard Chemoradiation With Adjuvant Chemotherapy Standard Chemoradiation (CRT) followed by 4 cycles of carboplatin and paclitaxel (Adjuvant)
Overall Study Ineligible	5	2

Baseline Characteristics

Cisplatin and Radiation Therapy With or Without Carboplatin and Paclitaxel in Patients With Locally Advanced Cervical Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Chemoradiation n=456 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin was given during the radiation at a dose of 40mg/m2 weekly for 5 doses to all patients.	Standard Chemoradiation With Adjuvant Chemotherapy n=463 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin will be given during the radiation at a dose of 40mg/m2 weekly for 5 doses to all patients. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients in Arm B were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.	Total n=919 Participants Total of all reporting groups
Age, Customized < 40 years	139 Participants n=5 Participants	146 Participants n=7 Participants	285 Participants n=5 Participants
Age, Customized 40 - 49 years	148 Participants n=5 Participants	130 Participants n=7 Participants	278 Participants n=5 Participants
Age, Customized 50 - 59 years	103 Participants n=5 Participants	117 Participants n=7 Participants	220 Participants n=5 Participants
Age, Customized > 60 years	66 Participants n=5 Participants	70 Participants n=7 Participants	136 Participants n=5 Participants
Sex: Female, Male Female	456 Participants n=5 Participants	463 Participants n=7 Participants	919 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) Asian	22 Participants n=5 Participants	31 Participants n=7 Participants	53 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Black or African American	68 Participants n=5 Participants	53 Participants n=7 Participants	121 Participants n=5 Participants
Race (NIH/OMB) White	326 Participants n=5 Participants	337 Participants n=7 Participants	663 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	29 Participants n=5 Participants	29 Participants n=7 Participants	58 Participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years from study randomization

Population: Eligible subjects

Outcome measures

Outcome measures
Measure	Standard Chemoradiation n=456 Participants Patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses	Standard Chemoradiation With Adjuvant Chemotherapy n=463 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.
Overall Survival Rate at 5 Years	71 Percentage of participants Interval 66.0 to 75.0	72 Percentage of participants Interval 67.0 to 76.0

SECONDARY outcome

Timeframe: 5 years from study randomization

Population: Eligible participants

Estimate for probability of progression free at 5 years by Kaplan-Meier method, where progression-free survival is defined as the time from randomization to the time of disease progression, death from any cause or date of last contact, whichever occurs first. Disease progression is defined by increasing clinical, radiological or pathological evidence of disease from participant entry to when investigator deems a progression. RECIST V1.0 was not used to determine response on this study.

Outcome measures

Outcome measures
Measure	Standard Chemoradiation n=456 Participants Patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses	Standard Chemoradiation With Adjuvant Chemotherapy n=463 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.
Progression-free Survival Rate at 5 Years	62 Percentage of participants Interval 57.0 to 66.0	63 Percentage of participants Interval 58.0 to 68.0

SECONDARY outcome

Timeframe: 1 year after randomization

Population: Arm A:eligible participants who received at least one dose of cisplatin and/or any dose of radiotherapy. Arm B: eligible participants who received at least one dose of adjuvant chemotherapy (carboplatin, paclitaxel, cisplatin or docetaxel)

Number of participants with a maximum grade of 3 or higher for pre-specified adverse events that occurred during the first year after randomization. Adverse events are graded and categorized using CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Standard Chemoradiation n=453 Participants Patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses	Standard Chemoradiation With Adjuvant Chemotherapy n=361 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Abdominal pain	13 Participants	14 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Alanine aminotransferase increased	4 Participants	2 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Allergic reaction/hypersensitivity	1 Participants	2 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Alopecia	0 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Anemia	32 Participants	64 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Aspartate aminotransferase increased	3 Participants	2 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Colitis	2 Participants	2 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Colonic obstruction	1 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Creatinine Increased	3 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Cystitis noninfective	1 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Dehydration	13 Participants	9 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Dermatitis radiation	1 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Diarrhea	21 Participants	20 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Enterocolitis	2 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Fatigue	7 Participants	9 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Febrile Neutropenia	9 Participants	9 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Female genital tract fistula	4 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Hearing impaired	0 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Hemorrhage bladder	3 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Hemorrhage rectum	1 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Lymphocyte count decreased	208 Participants	211 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Mucositis oral	2 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Myalgia	0 Participants	3 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Nausea	11 Participants	11 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Neutrophil count decreased	33 Participants	71 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Pain in extremity	3 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Pelvic pain	11 Participants	6 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Perineal pain	1 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Peripheral motor neuropathy	0 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Peripheral sensory neuropathy	1 Participants	16 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Platelet count decreased	5 Participants	16 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Proctitis	2 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Small intestinal obstruction	1 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Thrombosis/Thrombus/Embolism	7 Participants	7 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Tumor pain	6 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Urinary tract pain	1 Participants	0 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Uterine obstruction	1 Participants	2 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Vaginal Dryness	0 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Vaginal pain	3 Participants	1 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Vaginal stricture	4 Participants	4 Participants
Number of Participants With Adverse Events (Grade 3 or Higher) in First Year Vomiting	9 Participants	15 Participants

SECONDARY outcome

Timeframe: through study completion an average of 60 months

Population: Eligible participants. The "No Progression recorded group" included participants who died due to any causes without documented progression.

Number of patients for the site of disease recurrence. Disease was considered as persistent if participant had evidence of disease at study entry and disease did not progress during study. Disease status was considered locoregional alone if a participant had disease progression in the pelvis region including vagina after study entry. Disease status was considered distant if a participant had disease progression outside the pelvis (for example the abdomen and lung) after study entry. Criteria used to determine the no progression group includes participants that expired without documentation of progression.

Outcome measures

Outcome measures
Measure	Standard Chemoradiation n=456 Participants Patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses	Standard Chemoradiation With Adjuvant Chemotherapy n=463 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.
Patterns of Disease Recurrence Persistent	15 participants	5 participants
Patterns of Disease Recurrence Locoregional alone	33 participants	47 participants
Patterns of Disease Recurrence Distant with or without locoregional	51 participants	42 participants
Patterns of Disease Recurrence Other/Unknown	53 participants	37 participants
Patterns of Disease Recurrence No Progression recorded	304 participants	332 participants

SECONDARY outcome

Timeframe: Average duration of 7 weeks

Population: Eligible and received radiotherapy

Radiation protocol compliance measured by external beam dose delivered

Outcome measures

Outcome measures
Measure	Standard Chemoradiation n=450 Participants Patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses	Standard Chemoradiation With Adjuvant Chemotherapy n=448 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.
Radiation Protocol Compliance	45.6 Gray Interval 1.8 to 85.0	45.7 Gray Interval 4.5 to 90.0

SECONDARY outcome

Timeframe: Baseline and 12 months

Population: Eligible participants with Quality of Life at baseline and 12 months

Quality of Life measured by change of global health status score from baseline to 12 months follow-up. A cancer-specific questionnaire with 30 items which summarize as five functioning scales, a global health status/quality of life scale, three symptom scales and six single items assessing additional symptoms and perceived financial impact. The minimum global health status score was 0 and the maximum global health status score was 100. A higher global health status score means better outcome.

Outcome measures

Outcome measures
Measure	Standard Chemoradiation n=165 Participants Patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses	Standard Chemoradiation With Adjuvant Chemotherapy n=174 Participants patients receive 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, patients were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2.
Quality of Life for Global Health Status	1.7 score on a scale Standard Deviation 22.8	2.4 score on a scale Standard Deviation 26.3

Adverse Events

Standard Chemoradiation

Serious events: 98 serious events

Other events: 438 other events

Deaths: 123 deaths

Standard Chemoradiation With Adjuvant Chemotherapy

Serious events: 107 serious events

Other events: 360 other events

Deaths: 109 deaths

Serious adverse events

Serious adverse events
Measure	Standard Chemoradiation n=453 participants at risk 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses. At risk population includes eligible participants who received at least one dose of cisplatin and/or any dose of radiotherapy.	Standard Chemoradiation With Adjuvant Chemotherapy n=361 participants at risk 45 - 50.4 Gy external beam radiation therapy (EBRT) delivered in fractions of 1.8 Gy to the pelvis, followed by brachytherapy. Cisplatin given during the radiation at a dose of 40mg/m2 weekly for 5 doses to all patients. Within 4 weeks of completion of all radiation treatment, and following recovery from toxicities, participants were treated with an additional 4 cycles of 3 weekly adjuvant chemotherapy using carboplatin AUC 5 and paclitaxel 155 mg/m2. At risk population includes eligible participants who received at least one dose of adjuvant chemotherapy (carboplatin, paclitaxel, cisplatin or docetaxel).
General disorders General disorders NOS	21.6% 98/453 • Number of events 98 • Through study completion with a median follow-up being 60 months. Specific Serious Adverse Events were not provided, an overall number was provided. Therefore, the term "General disorders" was used to satisfy reporting requirements. All-Cause Mortality includes all eligible participants. Serious Adverse Events and Other Adverse Events include only eligible participants who received at least one dose of cisplatin and/or any dose of radiotherapy for Standard Chemo arm and eligible participants who received at least one dose of adjuvant chemo in the second arm	29.6% 107/361 • Number of events 107 • Through study completion with a median follow-up being 60 months. Specific Serious Adverse Events were not provided, an overall number was provided. Therefore, the term "General disorders" was used to satisfy reporting requirements. All-Cause Mortality includes all eligible participants. Serious Adverse Events and Other Adverse Events include only eligible participants who received at least one dose of cisplatin and/or any dose of radiotherapy for Standard Chemo arm and eligible participants who received at least one dose of adjuvant chemo in the second arm

Other adverse events

Additional Information

Linda Gedeon for Wei Deng

NRG Oncology

Phone: 716-845-1169

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60