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An Ovarian, Primary Peritoneal or Fallopian Tube Cancer Study for Patients That Have Not Received Prior Chemotherapy

Sponsor
Eli Lilly and Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00191646
Collaborator
(none)
919
Enrollment
55
Locations
2
Arms
82
Duration (Months)
16.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase III randomized study comparing induction treatments of Gemcitabine and Carboplatin versus Paclitaxel and Carboplatin, with or without consolidation therapy for patients that do not have any evidence of disease after completion of six cycles of induction therapy. Patients with disease after induction therapy will crossover to receive single agent therapy.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This study (Study B9E-US-S302) is a multicenter, comparative, open-label randomized, superiority, trial evaluating Gemcitabine and Carboplatin to the standard of care. Both treatment arms will be given the option to receive elective consolidation therapy of Paclitaxel 135 mg/m^2 given every 28 days for one year. Patients not achieving a complete response will crossover to the opposite single agent.

Study Design

Study Type:
Interventional
Actual Enrollment :
919 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Randomized Trial of Induction Chemotherapy With Gemcitabine and Carboplatin Followed by Elective Paclitaxel Consolidation Versus Paclitaxel and Carboplatin Followed by Elective Paclitaxel Consolidation in Patients With Primary Epithelial Ovarian, Primary Peritoneal Cancer or Fallopian Tube Carcinoma
Study Start Date :
Oct 1, 2002
Actual Primary Completion Date :
Aug 1, 2009
Actual Study Completion Date :
Aug 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: Gemcitabine/Carboplatin

Gemcitabine 1000 milligrams per meter square (mg/m^2) Day 1 and Day 8, Carboplatin Area Under the Curve (AUC) 5 Day 1, six 21-day cycles

Drug: Gemcitabine
1000 mg/m^2, Intravenously (IV), day 1 and day 8 every (q) 21 days x 6 cycles If anything other than complete response in Paclitaxel arm patients, 1000 mg/m^2, IV, day 1 and day 8 q 21 days until complete response, disease progression or unacceptable toxicity
Other Names:
  • LY188011
  • Gemzar

    • Drug: Carboplatin
    Gemcitabine/Carboplatin AUC 5, IV, Day 1, q 21 days x 6 cycles Paclitaxel/Carboplatin AUC 6, IV, Day 1, q 21 days x 6 cycles
    Active Comparator: Paclitaxel/Carboplatin

    Paclitaxel 175 milligrams per meter square (mg/m^2) administered intravenously (IV) Day 1 Carboplatin AUC 6 Day 1, six 21 day cycles

    Drug: Paclitaxel
    175 mg/m^2, IV, Day 1, q 21 days x 6 cycles If complete response both Paclitaxel and Gemcitabine arms may elect to receive consolidation therapy, 135 mg/m^2, IV, 3 hours q 28 days x 12 cycles (1 year) If no complete response, then Gemcitabine arm patients may receive 175 mg/m^2, IV, Day 1, q 21 days until complete response, disease progression or unacceptable toxicity

    Drug: Carboplatin
    Gemcitabine/Carboplatin AUC 5, IV, Day 1, q 21 days x 6 cycles Paclitaxel/Carboplatin AUC 6, IV, Day 1, q 21 days x 6 cycles

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) [Baseline to measured progressive disease or death up to 82 months]

      Progression free survival was defined as the duration from the date of randomization to the first date of documented disease progression or death from any cause. Tumor assessments were performed every three 21-day cycles during induction and crossover. Progression free survival was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies.

    Secondary Outcome Measures

    1. Proportion of Participants With Response (Response Rate) [Baseline to measured progressive disease up to 82 months]

      Response rate (RR) = proportion of participants with best overall Complete Response (CR: disappearance of all target lesions [TL]) or Partial Response (PR: 30% decrease in sum of longest diameter of TL). Induction therapy RR = number of participants with CR or PR during induction divided by number of participants with measurable disease at baseline (TL measurement during screening). Crossover therapy RR = number of participants with CR or PR during crossover divided by number of participants with measurable disease at baseline (latest TL measurement by first dose date of crossover therapy).

    2. Time to Treatment Failure [Baseline to stopping treatment up to 82 months]

      Time to treatment failure was defined as the duration from date of randomization to the date of the first of the following events: early discontinuation of study therapy; progression of disease, or death due to any cause. Time to treatment failure will be censored at the date of the last follow-up visit for participants who did not discontinue early, who are still alive, and who have not progressed. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies.

    3. Overall Survival [Baseline to death from any cause up to 82 months]

      Overall survival is defined as the duration from baseline to death. For participants who are still alive at the data cut-off date, survival will be censored at the last contact date. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    • Patients with a histologic diagnosis of primary peritoneal carcinoma, epithelial ovarian carcinoma or fallopian tube carcinoma Stage IC, II, III or IV.

    • All patients must have had surgery for fallopian, ovarian or peritoneal carcinoma to establish the diagnosis and have tissue available for histologic evaluation and confirmation of organ of origin.

    • Patients must be enrolled no more than twelve weeks postoperatively.

    • Patients must be willing to receive their chemotherapy drugs intravenously, as intraperitoneal therapy is not part of this trial.

    Key Exclusion Criteria:

    • Patients with a current diagnosis of epithelial ovarian tumor of low malignant potential (Borderline carcinomas) are not eligible.

    • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded

    • Patients who have received prior chemotherapy for any abdominal or pelvic tumor are excluded

    • With the exception of non-melanoma skin cancer and other specific malignancies patients who had (or have) any evidence of the other cancer present within the last 5 years or whose previous cancer treatment contraindicates this protocol therapy are excluded.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Phoenix Arizona United States 85006
    2 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Little Rock Arkansas United States 72205
    3 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Los Gatos California United States 95032
    4 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Modesto California United States 95350
    5 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. San Diego California United States 92121
    6 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Englewood Colorado United States 80113
    7 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Newark Delaware United States 19713
    8 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Fort Myers Florida United States 33901
    9 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. South Miami Florida United States 33143
    10 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Sunrise Florida United States 33323
    11 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Atlanta Georgia United States 30342
    12 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Savannah Georgia United States 31404
    13 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Palatine Illinois United States 60067
    14 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Indianapolis Indiana United States 46260
    15 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. South Bend Indiana United States 46617
    16 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Metairie Louisiana United States 70006
    17 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. New Orleans Louisiana United States 70121
    18 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Scarborough Maine United States 04074
    19 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Detroit Michigan United States 48201
    20 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Grand Rapids Michigan United States 49546
    21 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Duluth Minnesota United States 55805
    22 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Minneapolis Minnesota United States 55455
    23 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Rochester Minnesota United States 55905
    24 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Kansas City Missouri United States 64111
    25 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. St Louis Missouri United States 63141
    26 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Billings Montana United States 59107
    27 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Las Vegas Nevada United States 89109
    28 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Reno Nevada United States 89502
    29 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Hackensack New Jersey United States 07601
    30 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Rochester New York United States 14620
    31 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Chapel Hill North Carolina United States 27599
    32 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Charlotte North Carolina United States 28204
    33 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Durham North Carolina United States 27710
    34 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Greenville North Carolina United States 27858
    35 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Columbus Ohio United States 43222
    36 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Dayton Ohio United States 45429
    37 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Oklahoma City Oklahoma United States 73112
    38 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Dunmore Pennsylvania United States 18512
    39 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Johnstown Pennsylvania United States 15905
    40 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Pittsburgh Pennsylvania United States 15224
    41 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Sayre Pennsylvania United States 18840
    42 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Providence Rhode Island United States 02905
    43 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Charleston South Carolina United States 29425
    44 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Columbia South Carolina United States 29210
    45 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Greenville South Carolina United States 29601
    46 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Chattanooga Tennessee United States 37404
    47 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Knoxville Tennessee United States 37920
    48 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Memphis Tennessee United States 38120
    49 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Austin Texas United States 78735
    50 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Lubbock Texas United States 79410
    51 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Salt Lake City Utah United States 84106
    52 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Roanoke Virginia United States 24014
    53 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Seattle Washington United States 98104
    54 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. Madison Wisconsin United States 53792
    55 For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. San Juan Puerto Rico 009362712

    Sponsors and Collaborators

    • Eli Lilly and Company

    Investigators

    • Study Director: Call 1-877-CTLILLY (1-877-285-4559) OR 1-317-615-4559 MON-FRI 9AM -5PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00191646
    Other Study ID Numbers:
    • 6891
    • B9E-US-S302
    First Posted:
    Sep 19, 2005
    Last Update Posted:
    Mar 4, 2011
    Last Verified:
    Feb 1, 2011
    Additional relevant MeSH terms:
    Neoplasms
    Ovarian Neoplasms
    Peritoneal Neoplasms
    Fallopian Tube Neoplasms
    Genital Neoplasms, Female
    Pelvic Neoplasms
    Gemcitabine
    Paclitaxel
    Carboplatin

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail 919 patients were randomized, only 831 randomized patients were included in any analyses. 85 randomized patients were excluded due to significant noncompliant issues and 3 patients were excluded due to unavailable data.
    Arm/Group Title Gemcitabine/Carboplatin Paclitaxel/Carboplatin
    Arm/Group Description Induction: Gemcitabine 1000 mg/m^2 Days 1 and 8 followed by Carboplatin Area Under the Curve (AUC) 5 Day 1; every 21-days. Consolidation (gemcitabine to paclitaxel): Paclitaxel 135 mg/m^2 Intravenous Piggy-Back (IVPB), 3 hours every 28 days for 12 cycles (one year). Paclitaxel (crossover): Single agent Paclitaxel 175 mg/m^2 day 1 to be repeated every 21 days. Induction: Paclitaxel 175 mg/m^2 and Carboplatin AUC 6 Day 1, every 21 days. Consolidation (paclitaxel to paclitaxel): Paclitaxel 135 mg/m^2 IVPB, 3 hours every 28 days for 12 cycles (one year). Gemcitabine (crossover): Single agent Gemcitabine 1000 mg/m^2 days 1, 8 to be repeated every 21 days.
    Period Title: Overall Study
    STARTED 417 414
    Received Induction Therapy 411 409
    Received Consolidation Therapy 169 183
    Received Crossover Therapy 77 78
    COMPLETED 246 261
    NOT COMPLETED 171 153

    Baseline Characteristics

    Arm/Group Title Gemcitabine/Carboplatin Paclitaxel/Carboplatin Total
    Arm/Group Description Induction: Gemcitabine 1000 mg/m^2 Days 1 and 8 followed by Carboplatin Area Under the Curve (AUC) 5 Day 1; every 21-days. Consolidation (gemcitabine to paclitaxel): Paclitaxel 135 mg/m^2 Intravenous Piggy-Back (IVPB), 3 hours every 28 days for 12 cycles (one year). Paclitaxel (crossover): Single agent Paclitaxel 175 mg/m^2 day 1 to be repeated every 21 days. Induction: Paclitaxel 175 mg/m^2 and Carboplatin AUC 6 Day 1, every 21 days. Consolidation (paclitaxel to paclitaxel): Paclitaxel 135 mg/m^2 IVPB, 3 hours every 28 days for 12 cycles (one year). Gemcitabine (crossover): Single agent Gemcitabine 1000 mg/m^2 days 1, 8 to be repeated every 21 days. Total of all reporting groups
    Overall Participants 417 414 831
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    59.7
    (11.4)
    60.3
    (10.8)
    60.0
    (11.1)
    Sex: Female, Male (Count of Participants)
    Female
    417
    100%
    414
    100%
    831
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (participants) [Number]
    Caucasian
    379
    90.9%
    379
    91.5%
    758
    91.2%
    Black or African American
    12
    2.9%
    13
    3.1%
    25
    3%
    Asian
    5
    1.2%
    5
    1.2%
    10
    1.2%
    Native American
    2
    0.5%
    1
    0.2%
    3
    0.4%
    Other
    19
    4.6%
    16
    3.9%
    35
    4.2%
    Organ of Origin (participants) [Number]
    Ovary
    355
    85.1%
    362
    87.4%
    717
    86.3%
    Peritoneum
    56
    13.4%
    50
    12.1%
    106
    12.8%
    Missing Data
    6
    1.4%
    2
    0.5%
    8
    1%
    Extent of Residual Disease (participants) [Number]
    Measurable
    139
    33.3%
    114
    27.5%
    253
    30.4%
    Non-measurable
    276
    66.2%
    300
    72.5%
    576
    69.3%
    Missing Data
    2
    0.5%
    0
    0%
    2
    0.2%
    Zubrod Performance Status (participants) [Number]
    0
    239
    57.3%
    232
    56%
    471
    56.7%
    1
    139
    33.3%
    157
    37.9%
    296
    35.6%
    2
    27
    6.5%
    16
    3.9%
    43
    5.2%
    >= 3
    0
    0%
    0
    0%
    0
    0%
    Missing Data
    12
    2.9%
    9
    2.2%
    21
    2.5%
    International Federation of Gynecology and Obstetrics (FIGO) Stage at Initial Surgery (participants) [Number]
    Stage Ic
    21
    5%
    22
    5.3%
    43
    5.2%
    Stage II
    44
    10.6%
    39
    9.4%
    83
    10%
    Stage III
    284
    68.1%
    289
    69.8%
    573
    69%
    Stage IV
    68
    16.3%
    63
    15.2%
    131
    15.8%
    Missing Data
    0
    0%
    1
    0.2%
    1
    0.1%
    Histology (participants) [Number]
    Mucinous
    10
    2.4%
    10
    2.4%
    20
    2.4%
    Serous
    283
    67.9%
    276
    66.7%
    559
    67.3%
    Endometroid
    44
    10.6%
    40
    9.7%
    84
    10.1%
    Undifferentiated
    7
    1.7%
    7
    1.7%
    14
    1.7%
    Clear Cell
    21
    5%
    23
    5.6%
    44
    5.3%
    Mixed Epithelial
    9
    2.2%
    13
    3.1%
    22
    2.6%
    Transitional Cell
    3
    0.7%
    1
    0.2%
    4
    0.5%
    Malignant Brenner's Tumor
    0
    0%
    0
    0%
    0
    0%
    Adenocarcinoma Not Otherwise Specified (NOS)
    22
    5.3%
    23
    5.6%
    45
    5.4%
    Other
    17
    4.1%
    21
    5.1%
    38
    4.6%
    Missing Data
    1
    0.2%
    0
    0%
    1
    0.1%
    Volume of Residual Tumor Following Debulking Surgery (participants) [Number]
    < 2 centimeters
    309
    74.1%
    314
    75.8%
    623
    75%
    >= 2 centimeters
    102
    24.5%
    96
    23.2%
    198
    23.8%
    Missing Data
    6
    1.4%
    4
    1%
    10
    1.2%
    CA-125 Units per milliliter at Baseline for All Patients (units per milliliter) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units per milliliter]
    492.772
    (1138.556)
    479.854
    (1117.040)
    486.329
    (1127.213)

    Outcome Measures

    1. Primary Outcome
    Title Progression Free Survival (PFS)
    Description Progression free survival was defined as the duration from the date of randomization to the first date of documented disease progression or death from any cause. Tumor assessments were performed every three 21-day cycles during induction and crossover. Progression free survival was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies.
    Time Frame Baseline to measured progressive disease or death up to 82 months

    Outcome Measure Data

    Analysis Population Description
    Intent to treat (ITT) population, which includes all randomized participants. 3 participants in the Gemcitabine/Carboplatin treatment sequence were excluded due to missing data, and 1 participant in the Paclitaxel/Carboplatin treatment sequence was excluded for missing data. G/C Arm: 292 events, 122 censored. P/C Arm: 279 events, 134 censored.
    Arm/Group Title Gemcitabine/Carboplatin Paclitaxel/Carboplatin
    Arm/Group Description Induction: Gemcitabine 1000 mg/m^2 Days 1 and 8 followed by Carboplatin Area Under the Curve (AUC) 5 Day 1; every 21-days. Consolidation (gemcitabine to paclitaxel): Paclitaxel 135 mg/m^2 Intravenous Piggy-Back (IVPB), 3 hours every 28 days for 12 cycles (one year). Paclitaxel (crossover): Single agent Paclitaxel 175 mg/m^2 day 1 to be repeated every 21 days. Induction: Paclitaxel 175 mg/m^2 and Carboplatin AUC 6 Day 1, every 21 days. Consolidation (paclitaxel to paclitaxel): Paclitaxel 135 mg/m^2 IVPB, 3 hours every 28 days for 12 cycles (one year). Gemcitabine (crossover): Single agent Gemcitabine 1000 mg/m^2 days 1, 8 to be repeated every 21 days.
    Measure Participants 414 413
    Median (95% Confidence Interval) [Months]
    20.0
    22.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gemcitabine/Carboplatin, Paclitaxel/Carboplatin
    Comments Using a two-sided log-rank test with a Type I error of 0.05, 636 events for PFS out of the 919 patients would give an 80% statistical power under the alternative hypothesis that the hazard ratio of the G/C arm versus the P/C arm was 0.08.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.199
    Comments
    Method Log Rank
    Comments
    2. Secondary Outcome
    Title Proportion of Participants With Response (Response Rate)
    Description Response rate (RR) = proportion of participants with best overall Complete Response (CR: disappearance of all target lesions [TL]) or Partial Response (PR: 30% decrease in sum of longest diameter of TL). Induction therapy RR = number of participants with CR or PR during induction divided by number of participants with measurable disease at baseline (TL measurement during screening). Crossover therapy RR = number of participants with CR or PR during crossover divided by number of participants with measurable disease at baseline (latest TL measurement by first dose date of crossover therapy).
    Time Frame Baseline to measured progressive disease up to 82 months

    Outcome Measure Data

    Analysis Population Description
    All ITT participants with measurable disease at baseline (screening) for induction period; all ITT participants who crossed over to single agent therapy and had measurable disease before or at crossover for crossover period. Participants in consolidation therapy achieved CR during induction therapy and were not included in analysis.
    Arm/Group Title Gemcitabine/Carboplatin (Induction) Paclitaxel/Carboplatin (Induction) Gemcitabine (Crossover) Paclitaxel (Crossover)
    Arm/Group Description Gemcitabine 1000 milligrams per meter square (mg/m^2) Day 1, Day 8, Carboplatin AUC 5 Day 1, six 21-day cycles Paclitaxel 175 milligrams per meter square (mg/m^2) administered intravenously (IV) Day 1 Carboplatin AUC 6 Day 1, six 21-day cycles Crossover (From Paclitaxel to Gemcitabine) - If no complete response on Paclitaxel, patient crossed over to receive Gemcitabine 1000 mg/m^2, IV, day 1 and day 8 q 21 days until complete response, disease progression or unacceptable toxicity Crossover (From Gemcitabine to Paclitaxel) - If no complete response on Gemcitabine, patient crossed over to receive Paclitaxel 175 mg/m^2, IV, day 1, q 21 days until complete response, disease progression or unacceptable toxicity
    Measure Participants 139 114 28 33
    Mean (95% Confidence Interval) [proportion of responders]
    0.676
    0.711
    0.357
    0.303
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gemcitabine/Carboplatin, Paclitaxel/Carboplatin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.771
    Comments
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Gemcitabine (Crossover), Paclitaxel (Crossover)
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.784
    Comments
    Method Fisher Exact
    Comments
    3. Secondary Outcome
    Title Time to Treatment Failure
    Description Time to treatment failure was defined as the duration from date of randomization to the date of the first of the following events: early discontinuation of study therapy; progression of disease, or death due to any cause. Time to treatment failure will be censored at the date of the last follow-up visit for participants who did not discontinue early, who are still alive, and who have not progressed. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies.
    Time Frame Baseline to stopping treatment up to 82 months

    Outcome Measure Data

    Analysis Population Description
    Intent to treat (ITT) population, which includes all randomized participants. 3 participants in the Gemcitabine/Carboplatin treatment sequence were excluded due to missing data, and 1 participant in the Paclitaxel/Carboplatin treatment sequence was excluded for missing data. G/C Arm: 336 events, 78 censored. P/C Arm: 330 events, 83 censored.
    Arm/Group Title Gemcitabine/Carboplatin Paclitaxel/Carboplatin
    Arm/Group Description Induction: Gemcitabine 1000 mg/m^2 Days 1 and 8 followed by Carboplatin Area Under the Curve (AUC) 5 Day 1; every 21-days. Consolidation (gemcitabine to paclitaxel): Paclitaxel 135 mg/m^2 Intravenous Piggy-Back (IVPB), 3 hours every 28 days for 12 cycles (one year). Paclitaxel (crossover): Single agent Paclitaxel 175 mg/m^2 day 1 to be repeated every 21 days. Induction: Paclitaxel 175 mg/m^2 and Carboplatin AUC 6 Day 1, every 21 days. Consolidation (paclitaxel to paclitaxel): Paclitaxel 135 mg/m^2 IVPB, 3 hours every 28 days for 12 cycles (one year). Gemcitabine (crossover): Single agent Gemcitabine 1000 mg/m^2 days 1, 8 to be repeated every 21 days.
    Measure Participants 414 413
    Median (95% Confidence Interval) [months]
    13.0
    13.1
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gemcitabine/Carboplatin, Paclitaxel/Carboplatin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.621
    Comments
    Method Log Rank
    Comments
    4. Secondary Outcome
    Title Overall Survival
    Description Overall survival is defined as the duration from baseline to death. For participants who are still alive at the data cut-off date, survival will be censored at the last contact date. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies.
    Time Frame Baseline to death from any cause up to 82 months

    Outcome Measure Data

    Analysis Population Description
    Intent to treat (ITT) population, which includes all randomized participants. 3 participants in the Gemcitabine/Carboplatin treatment sequence were excluded due to missing data, and 1 participant in the Paclitaxel/Carboplatin treatment sequence was excluded for missing data. G/C Arm: 194 events, 220 censored. P/C Arm: 159 events, 254 censored.
    Arm/Group Title Gemcitabine/Carboplatin Paclitaxel/Carboplatin
    Arm/Group Description Induction: Gemcitabine 1000 mg/m^2 Days 1 and 8 followed by Carboplatin Area Under the Curve (AUC) 5 Day 1; every 21-days. Consolidation (gemcitabine to paclitaxel): Paclitaxel 135 mg/m^2 Intravenous Piggy-Back (IVPB), 3 hours every 28 days for 12 cycles (one year). Paclitaxel (crossover): Single agent Paclitaxel 175 mg/m^2 day 1 to be repeated every 21 days. Induction: Paclitaxel 175 mg/m^2 and Carboplatin AUC 6 Day 1, every 21 days. Consolidation (paclitaxel to paclitaxel): Paclitaxel 135 mg/m^2 IVPB, 3 hours every 28 days for 12 cycles (one year). Gemcitabine (crossover): Single agent Gemcitabine 1000 mg/m^2 days 1, 8 to be repeated every 21 days.
    Measure Participants 414 413
    Median (95% Confidence Interval) [months]
    43.8
    57.3
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Gemcitabine/Carboplatin, Paclitaxel/Carboplatin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.013
    Comments
    Method Log Rank
    Comments

    Adverse Events

    Time Frame
    Adverse Event Reporting Description A participant was randomized to P/C but treated with G/C, and thus included in the P/C arm ITT population (disposition and efficacy tables) and included in the G/C arm of treated population (AE tables). This results in an inconsistency between number of participants analyzed and participant flow module.
    Arm/Group Title Gemcitabine/Carboplatin Induction Paclitaxel/Carboplatin Induction Consolidation (Gemcitabine to Paclitaxel) Consolidation (Paclitaxel to Paclitaxel) Crossover (Paclitaxel to Gemcitabine) Crossover (Gemcitabine to Paclitaxel)
    Arm/Group Description Gemcitabine 1000 milligrams per meter square (mg/m2) Day 1, Day 8, Carboplatin AUC 5 Day 1, 6 21 day cycles Paclitaxel 175 milligrams per meter square (mg/m2) administered intravenously (IV) Day 1 Carboplatin AUC 6 Day 1, 6 21 day cycles Paclitaxel 135mg/m2 IV/3 hours every 28 days for 12 cycles (one year). Paclitaxel 135mg/m2 IV/3 hours every 28 days for 12 cycles (one year). Single agent Gemcitabine 1000mg/m2 IV, Day 1, Day 8 to be repeated every 21 days. Single agent Paclitaxel 175mg/m2 IV Day 1 to be repeated every 21 days.
    All Cause Mortality
    Gemcitabine/Carboplatin Induction Paclitaxel/Carboplatin Induction Consolidation (Gemcitabine to Paclitaxel) Consolidation (Paclitaxel to Paclitaxel) Crossover (Paclitaxel to Gemcitabine) Crossover (Gemcitabine to Paclitaxel)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Gemcitabine/Carboplatin Induction Paclitaxel/Carboplatin Induction Consolidation (Gemcitabine to Paclitaxel) Consolidation (Paclitaxel to Paclitaxel) Crossover (Paclitaxel to Gemcitabine) Crossover (Gemcitabine to Paclitaxel)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 96/412 (23.3%) 72/408 (17.6%) 14/169 (8.3%) 12/183 (6.6%) 8/78 (10.3%) 8/77 (10.4%)
    Blood and lymphatic system disorders
    Anaemia 2/412 (0.5%) 3 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Febrile neutropenia 5/412 (1.2%) 5 9/408 (2.2%) 11 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 1/77 (1.3%) 2
    Leukocytosis 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Leukopenia 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Neutropenia 2/412 (0.5%) 2 3/408 (0.7%) 3 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pancytopenia 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Splenic infarction 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Thrombocytopenia 4/412 (1%) 4 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Cardiac disorders
    Angina unstable 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Arrhythmia supraventricular 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Atrial fibrillation 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Cardiac failure congestive 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Cardio-respiratory arrest 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Myocardial infarction 0/412 (0%) 0 1/408 (0.2%) 1 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Supraventricular tachycardia 1/412 (0.2%) 1 3/408 (0.7%) 3 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Tachycardia 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Gastrointestinal disorders
    Abdominal hernia 0/412 (0%) 0 0/408 (0%) 0 1/169 (0.6%) 1 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Abdominal pain 6/412 (1.5%) 7 5/408 (1.2%) 6 1/169 (0.6%) 1 2/183 (1.1%) 2 0/78 (0%) 0 0/77 (0%) 0
    Abdominal pain upper 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Constipation 2/412 (0.5%) 2 3/408 (0.7%) 4 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Diarrhoea 1/412 (0.2%) 1 1/408 (0.2%) 1 2/169 (1.2%) 2 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Duodenal ulcer perforation 0/412 (0%) 0 0/408 (0%) 0 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Enterovesical fistula 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Faecaloma 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Gastritis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Gastrointestinal haemorrhage 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Gastrointestinal necrosis 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Gastrointestinal obstruction 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Haematemesis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Haematochezia 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Ileus 0/412 (0%) 0 1/408 (0.2%) 1 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Impaired gastric emptying 0/412 (0%) 0 0/408 (0%) 0 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Intestinal infarction 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Intestinal obstruction 2/412 (0.5%) 2 4/408 (1%) 4 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    Intestinal perforation 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Nausea 12/412 (2.9%) 16 8/408 (2%) 8 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Oesophagitis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pancreatitis acute 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Retroperitoneum cyst 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Small intestinal obstruction 2/412 (0.5%) 2 4/408 (1%) 4 2/169 (1.2%) 2 1/183 (0.5%) 1 0/78 (0%) 0 1/77 (1.3%) 1
    Upper gastrointestinal haemorrhage 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Vomiting 10/412 (2.4%) 13 9/408 (2.2%) 10 1/169 (0.6%) 1 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    General disorders
    Chest pain 2/412 (0.5%) 3 3/408 (0.7%) 4 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Chills 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Disease progression 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Fatigue 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Infusion related reaction 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pain 0/412 (0%) 0 1/408 (0.2%) 1 2/169 (1.2%) 2 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pyrexia 8/412 (1.9%) 10 2/408 (0.5%) 2 0/169 (0%) 0 0/183 (0%) 0 2/78 (2.6%) 2 1/77 (1.3%) 1
    Sensation of pressure 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hepatobiliary disorders
    Cholangitis 1/412 (0.2%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Cholelithiasis 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hepatitis 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hyperbilirubinaemia 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Jaundice 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Immune system disorders
    Drug hypersensitivity 1/412 (0.2%) 1 2/408 (0.5%) 2 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Infections and infestations
    Bacteraemia 0/412 (0%) 0 1/408 (0.2%) 1 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Bronchopneumonia 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Catheter bacteraemia 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Catheter related infection 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Catheter sepsis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Cellulitis 2/412 (0.5%) 2 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Central line infection 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Clostridial infection 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Clostridium difficile colitis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Diverticulitis 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Empyema 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Gastrointestinal infection 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Herpes zoster 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Infected cyst 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Neutropenic sepsis 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pneumonia 3/412 (0.7%) 3 2/408 (0.5%) 3 2/169 (1.2%) 2 1/183 (0.5%) 1 1/78 (1.3%) 1 0/77 (0%) 0
    Pneumonia primary atypical 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Postoperative abscess 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Postoperative wound infection 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Sepsis 0/412 (0%) 0 3/408 (0.7%) 3 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Sepsis syndrome 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Thrombophlebitis septic 1/412 (0.2%) 1 0/408 (0%) 0 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Upper respiratory tract infection 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Urinary tract infection 6/412 (1.5%) 9 4/408 (1%) 4 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Urosepsis 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Viral infection 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Wound infection 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Infection/febrile neutropenia 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Injury, poisoning and procedural complications
    Contusion 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Drug administration error 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Fall 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    Foot fracture 0/412 (0%) 0 0/408 (0%) 0 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hip fracture 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Procedural pain 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Rib fracture 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 2 0/77 (0%) 0
    Spinal compression fracture 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Wound dehiscence 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Investigations
    Absolute neutrophil count/absolute granulocyte count 21/412 (5.1%) 24 14/408 (3.4%) 16 1/169 (0.6%) 1 1/183 (0.5%) 1 1/78 (1.3%) 2 0/77 (0%) 0
    Blood creatinine increased 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Body temperature increased 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Haematocrit 1/412 (0.2%) 1 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hemoglobin 24/412 (5.8%) 28 3/408 (0.7%) 4 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    Liver function test abnormal 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 2 0/77 (0%) 0
    Platelet count 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Platelets 43/412 (10.4%) 53 5/408 (1.2%) 5 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    White blood cells 10/412 (2.4%) 12 3/408 (0.7%) 3 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Weight decreased 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hematologic 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Metabolism and nutrition disorders
    Anorexia 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Dehydration 6/412 (1.5%) 6 7/408 (1.7%) 8 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    Diabetes mellitus inadequate control 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Failure to thrive 0/412 (0%) 0 2/408 (0.5%) 2 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hyperglycaemia 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hypoglycaemia 0/412 (0%) 0 2/408 (0.5%) 2 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hypokalaemia 1/412 (0.2%) 1 3/408 (0.7%) 3 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hyponatraemia 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Hypovolaemia 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Musculoskeletal and connective tissue disorders
    Back pain 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/412 (0%) 0 1/408 (0.2%) 2 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Malignant neoplasm progression 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Nervous system disorders
    Cerebrovascular accident 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Convulsion 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Coordination abnormal 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Dizziness 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hypoglycaemic coma 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Paraesthesia 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Subarachnoid haemorrhage 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 2 0/77 (0%) 0
    Syncope 2/412 (0.5%) 2 0/408 (0%) 0 1/169 (0.6%) 1 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Psychiatric disorders
    Mental status changes 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Renal and urinary disorders
    Costovertebral angle tenderness 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Haematuria 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Hydronephrosis 1/412 (0.2%) 1 3/408 (0.7%) 3 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Nephrolithiasis 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Renal failure 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Renal failure acute 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Renal infarct 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Ureteric obstruction 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    Urinary tract disorder 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Reproductive system and breast disorders
    Female genital tract fistula 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Vaginal fistula 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Vaginal haemorrhage 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Dyspnoea 2/412 (0.5%) 2 2/408 (0.5%) 3 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Epistaxis 3/412 (0.7%) 3 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hypoxia 1/412 (0.2%) 1 2/408 (0.5%) 2 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pleural effusion 3/412 (0.7%) 4 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 1/78 (1.3%) 1 0/77 (0%) 0
    Pulmonary congestion 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pulmonary embolism 2/412 (0.5%) 2 5/408 (1.2%) 5 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Pulmonary oedema 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Respiratory depression 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Respiratory distress 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Respiratory failure 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Skin and subcutaneous tissue disorders
    Petechiae 2/412 (0.5%) 2 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Rash generalised 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Surgical and medical procedures
    Hospitalisation 1/412 (0.2%) 1 3/408 (0.7%) 3 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Pain management 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 1/183 (0.5%) 2 0/78 (0%) 0 0/77 (0%) 0
    Vascular disorders
    Deep vein thrombosis 6/412 (1.5%) 6 3/408 (0.7%) 3 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Haemorrhage 1/412 (0.2%) 1 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Hypotension 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Pelvic venous thrombosis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Thrombosis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 1/183 (0.5%) 1 0/78 (0%) 0 0/77 (0%) 0
    Vasculitis 0/412 (0%) 0 0/408 (0%) 0 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 1/77 (1.3%) 1
    Vena cava thrombosis 0/412 (0%) 0 1/408 (0.2%) 1 0/169 (0%) 0 0/183 (0%) 0 0/78 (0%) 0 0/77 (0%) 0
    Other (Not Including Serious) Adverse Events
    Gemcitabine/Carboplatin Induction Paclitaxel/Carboplatin Induction Consolidation (Gemcitabine to Paclitaxel) Consolidation (Paclitaxel to Paclitaxel) Crossover (Paclitaxel to Gemcitabine) Crossover (Gemcitabine to Paclitaxel)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 404/412 (98.1%) 394/408 (96.6%) 157/169 (92.9%) 170/183 (92.9%) 76/78 (97.4%) 73/77 (94.8%)
    Blood and lymphatic system disorders
    Lymphopenia 9/412 (2.2%) 25 10/408 (2.5%) 25 2/169 (1.2%) 4 4/183 (2.2%) 9 4/78 (5.1%) 10 1/77 (1.3%) 1
    Thrombocytopenia 22/412 (5.3%) 68 8/408 (2%) 12 1/169 (0.6%) 4 1/183 (0.5%) 7 4/78 (5.1%) 4 0/77 (0%) 0
    Ear and labyrinth disorders
    Tinnitus 18/412 (4.4%) 31 22/408 (5.4%) 39 8/169 (4.7%) 26 14/183 (7.7%) 39 0/78 (0%) 0 2/77 (2.6%) 8
    Eye disorders
    Vision blurred 15/412 (3.6%) 26 26/408 (6.4%) 50 9/169 (5.3%) 26 15/183 (8.2%) 33 3/78 (3.8%) 6 2/77 (2.6%) 3
    Visual disturbance 5/412 (1.2%) 5 11/408 (2.7%) 15 8/169 (4.7%) 15 8/183 (4.4%) 23 3/78 (3.8%) 5 4/77 (5.2%) 9
    Gastrointestinal disorders
    Abdominal distension 21/412 (5.1%) 32 11/408 (2.7%) 16 9/169 (5.3%) 24 13/183 (7.1%) 18 5/78 (6.4%) 12 5/77 (6.5%) 10
    Abdominal pain 88/412 (21.4%) 168 92/408 (22.5%) 148 29/169 (17.2%) 76 32/183 (17.5%) 68 14/78 (17.9%) 26 16/77 (20.8%) 30
    Abdominal pain upper 21/412 (5.1%) 27 16/408 (3.9%) 24 8/169 (4.7%) 13 7/183 (3.8%) 10 2/78 (2.6%) 2 4/77 (5.2%) 4
    Constipation 173/412 (42%) 400 170/408 (41.7%) 391 54/169 (32%) 154 62/183 (33.9%) 178 31/78 (39.7%) 66 25/77 (32.5%) 60
    Diarrhoea 83/412 (20.1%) 145 97/408 (23.8%) 187 43/169 (25.4%) 107 43/183 (23.5%) 111 12/78 (15.4%) 17 9/77 (11.7%) 19
    Dyspepsia 16/412 (3.9%) 21 17/408 (4.2%) 26 9/169 (5.3%) 24 14/183 (7.7%) 20 3/78 (3.8%) 6 5/77 (6.5%) 6
    Nausea 213/412 (51.7%) 504 205/408 (50.2%) 506 67/169 (39.6%) 191 46/183 (25.1%) 110 32/78 (41%) 67 21/77 (27.3%) 48
    Stomatitis 25/412 (6.1%) 33 23/408 (5.6%) 40 11/169 (6.5%) 18 8/183 (4.4%) 24 0/78 (0%) 0 3/77 (3.9%) 7
    Vomiting 95/412 (23.1%) 146 95/408 (23.3%) 154 19/169 (11.2%) 24 12/183 (6.6%) 20 14/78 (17.9%) 22 9/77 (11.7%) 20
    General disorders
    Asthenia 28/412 (6.8%) 39 34/408 (8.3%) 41 7/169 (4.1%) 12 8/183 (4.4%) 15 3/78 (3.8%) 3 2/77 (2.6%) 2
    Fatigue 281/412 (68.2%) 948 279/408 (68.4%) 912 108/169 (63.9%) 531 119/183 (65%) 558 56/78 (71.8%) 217 40/77 (51.9%) 160
    Oedema 20/412 (4.9%) 31 8/408 (2%) 13 3/169 (1.8%) 5 8/183 (4.4%) 18 5/78 (6.4%) 7 1/77 (1.3%) 1
    Oedema peripheral 46/412 (11.2%) 84 33/408 (8.1%) 53 18/169 (10.7%) 50 21/183 (11.5%) 64 5/78 (6.4%) 12 6/77 (7.8%) 8
    Pain 25/412 (6.1%) 31 38/408 (9.3%) 59 36/169 (21.3%) 76 26/183 (14.2%) 43 8/78 (10.3%) 12 4/77 (5.2%) 6
    Pyrexia 34/412 (8.3%) 47 19/408 (4.7%) 24 4/169 (2.4%) 4 6/183 (3.3%) 8 9/78 (11.5%) 10 4/77 (5.2%) 5
    Infections and infestations
    Nasopharyngitis 5/412 (1.2%) 5 5/408 (1.2%) 7 5/169 (3%) 7 6/183 (3.3%) 6 4/78 (5.1%) 4 0/77 (0%) 0
    Sinusitis 6/412 (1.5%) 6 13/408 (3.2%) 18 3/169 (1.8%) 3 10/183 (5.5%) 14 7/78 (9%) 8 1/77 (1.3%) 1
    Upper respiratory tract infection 12/412 (2.9%) 12 6/408 (1.5%) 8 7/169 (4.1%) 10 12/183 (6.6%) 13 4/78 (5.1%) 5 0/77 (0%) 0
    Urinary tract infection 28/412 (6.8%) 31 31/408 (7.6%) 41 10/169 (5.9%) 15 14/183 (7.7%) 19 4/78 (5.1%) 4 4/77 (5.2%) 5
    Injury, poisoning and procedural complications
    Contusion 31/412 (7.5%) 48 15/408 (3.7%) 28 9/169 (5.3%) 12 6/183 (3.3%) 19 0/78 (0%) 0 1/77 (1.3%) 2
    Investigations
    Alanine aminotransferase 24/412 (5.8%) 53 19/408 (4.7%) 33 4/169 (2.4%) 6 7/183 (3.8%) 21 5/78 (6.4%) 12 1/77 (1.3%) 3
    Alanine aminotransferase increased 64/412 (15.5%) 120 27/408 (6.6%) 46 10/169 (5.9%) 27 10/183 (5.5%) 17 11/78 (14.1%) 20 2/77 (2.6%) 10
    Anc/agc 378/412 (91.7%) 1638 361/408 (88.5%) 1531 88/169 (52.1%) 314 93/183 (50.8%) 325 68/78 (87.2%) 246 47/77 (61%) 173
    Aspartate aminotransferase increased 58/412 (14.1%) 100 21/408 (5.1%) 36 10/169 (5.9%) 21 13/183 (7.1%) 23 12/78 (15.4%) 19 3/77 (3.9%) 8
    Blood albumin decreased 18/412 (4.4%) 39 17/408 (4.2%) 36 2/169 (1.2%) 2 3/183 (1.6%) 4 4/78 (5.1%) 7 1/77 (1.3%) 1
    Blood alkaline phosphatase 23/412 (5.6%) 51 20/408 (4.9%) 32 6/169 (3.6%) 19 7/183 (3.8%) 12 3/78 (3.8%) 7 1/77 (1.3%) 1
    Blood alkaline phosphatase increased 52/412 (12.6%) 103 37/408 (9.1%) 68 13/169 (7.7%) 33 8/183 (4.4%) 38 8/78 (10.3%) 11 7/77 (9.1%) 12
    Blood glucose 11/412 (2.7%) 18 22/408 (5.4%) 32 12/169 (7.1%) 17 10/183 (5.5%) 46 0/78 (0%) 0 4/77 (5.2%) 10
    Blood glucose increased 46/412 (11.2%) 93 50/408 (12.3%) 108 26/169 (15.4%) 79 21/183 (11.5%) 55 10/78 (12.8%) 13 5/77 (6.5%) 18
    Blood sodium decreased 14/412 (3.4%) 28 23/408 (5.6%) 41 5/169 (3%) 7 7/183 (3.8%) 9 5/78 (6.4%) 7 1/77 (1.3%) 2
    Blood urea increased 19/412 (4.6%) 39 18/408 (4.4%) 28 22/169 (13%) 53 7/183 (3.8%) 20 3/78 (3.8%) 4 4/77 (5.2%) 21
    Carbon dioxide increased 18/412 (4.4%) 41 8/408 (2%) 11 12/169 (7.1%) 33 6/183 (3.3%) 11 4/78 (5.1%) 5 2/77 (2.6%) 4
    Haematocrit 24/412 (5.8%) 42 17/408 (4.2%) 33 1/169 (0.6%) 3 7/183 (3.8%) 12 1/78 (1.3%) 9 1/77 (1.3%) 1
    Hemoglobin 385/412 (93.4%) 1830 352/408 (86.3%) 1436 83/169 (49.1%) 338 103/183 (56.3%) 375 66/78 (84.6%) 270 54/77 (70.1%) 201
    Hepatic enzyme increased 5/412 (1.2%) 8 1/408 (0.2%) 1 6/169 (3.6%) 9 2/183 (1.1%) 2 5/78 (6.4%) 8 0/77 (0%) 0
    Liver function test abnormal 16/412 (3.9%) 19 9/408 (2.2%) 13 2/169 (1.2%) 12 1/183 (0.5%) 1 5/78 (6.4%) 11 2/77 (2.6%) 3
    Platelets 379/412 (92%) 1550 233/408 (57.1%) 631 36/169 (21.3%) 110 23/183 (12.6%) 72 61/78 (78.2%) 216 16/77 (20.8%) 31
    Protein total decreased 9/412 (2.2%) 10 15/408 (3.7%) 20 7/169 (4.1%) 17 1/183 (0.5%) 1 5/78 (6.4%) 6 3/77 (3.9%) 3
    White blood cells 380/412 (92.2%) 1714 350/408 (85.8%) 1507 88/169 (52.1%) 423 101/183 (55.2%) 442 68/78 (87.2%) 247 49/77 (63.6%) 208
    Weight decreased 37/412 (9%) 67 31/408 (7.6%) 45 6/169 (3.6%) 10 6/183 (3.3%) 7 1/78 (1.3%) 1 3/77 (3.9%) 5
    Weight increased 24/412 (5.8%) 60 15/408 (3.7%) 33 26/169 (15.4%) 100 31/183 (16.9%) 88 7/78 (9%) 16 5/77 (6.5%) 25
    Metabolism and nutrition disorders
    Anorexia 49/412 (11.9%) 82 57/408 (14%) 99 13/169 (7.7%) 22 5/183 (2.7%) 8 7/78 (9%) 15 8/77 (10.4%) 25
    Hyperglycaemia 45/412 (10.9%) 111 72/408 (17.6%) 158 36/169 (21.3%) 150 42/183 (23%) 152 10/78 (12.8%) 23 16/77 (20.8%) 53
    Hypoalbuminaemia 17/412 (4.1%) 35 11/408 (2.7%) 18 0/169 (0%) 0 0/183 (0%) 0 2/78 (2.6%) 7 5/77 (6.5%) 6
    Hypocalcaemia 14/412 (3.4%) 29 8/408 (2%) 12 2/169 (1.2%) 2 3/183 (1.6%) 3 3/78 (3.8%) 3 4/77 (5.2%) 5
    Hypokalaemia 29/412 (7%) 47 20/408 (4.9%) 29 6/169 (3.6%) 13 11/183 (6%) 18 2/78 (2.6%) 3 8/77 (10.4%) 13
    Hyponatraemia 14/412 (3.4%) 19 14/408 (3.4%) 24 6/169 (3.6%) 9 8/183 (4.4%) 15 0/78 (0%) 0 4/77 (5.2%) 7
    Musculoskeletal and connective tissue disorders
    Arthralgia 48/412 (11.7%) 86 108/408 (26.5%) 247 66/169 (39.1%) 192 53/183 (29%) 149 16/78 (20.5%) 32 25/77 (32.5%) 62
    Arthritis 8/412 (1.9%) 16 4/408 (1%) 6 4/169 (2.4%) 10 10/183 (5.5%) 33 2/78 (2.6%) 6 0/77 (0%) 0
    Back pain 47/412 (11.4%) 72 42/408 (10.3%) 81 19/169 (11.2%) 37 30/183 (16.4%) 76 9/78 (11.5%) 12 8/77 (10.4%) 12
    Bone pain 14/412 (3.4%) 22 33/408 (8.1%) 45 16/169 (9.5%) 38 8/183 (4.4%) 15 1/78 (1.3%) 1 6/77 (7.8%) 9
    Muscular weakness 15/412 (3.6%) 30 26/408 (6.4%) 46 8/169 (4.7%) 22 18/183 (9.8%) 69 3/78 (3.8%) 3 1/77 (1.3%) 1
    Musculoskeletal pain 25/412 (6.1%) 41 55/408 (13.5%) 97 37/169 (21.9%) 91 25/183 (13.7%) 53 8/78 (10.3%) 17 8/77 (10.4%) 13
    Myalgia 36/412 (8.7%) 62 100/408 (24.5%) 220 44/169 (26%) 130 38/183 (20.8%) 103 10/78 (12.8%) 23 17/77 (22.1%) 40
    Pain in extremity 27/412 (6.6%) 45 49/408 (12%) 75 18/169 (10.7%) 45 18/183 (9.8%) 62 8/78 (10.3%) 8 6/77 (7.8%) 6
    Nervous system disorders
    Dizziness 44/412 (10.7%) 65 34/408 (8.3%) 52 11/169 (6.5%) 22 14/183 (7.7%) 18 6/78 (7.7%) 10 5/77 (6.5%) 9
    Headache 40/412 (9.7%) 82 39/408 (9.6%) 75 20/169 (11.8%) 41 15/183 (8.2%) 28 4/78 (5.1%) 7 6/77 (7.8%) 14
    Hypoaesthesia 25/412 (6.1%) 36 53/408 (13%) 93 29/169 (17.2%) 70 33/183 (18%) 103 5/78 (6.4%) 14 12/77 (15.6%) 32
    Neuropathy 15/412 (3.6%) 28 65/408 (15.9%) 140 39/169 (23.1%) 122 51/183 (27.9%) 183 7/78 (9%) 20 19/77 (24.7%) 64
    Neuropathy peripheral 22/412 (5.3%) 58 99/408 (24.3%) 190 62/169 (36.7%) 207 68/183 (37.2%) 211 17/78 (21.8%) 39 23/77 (29.9%) 60
    Paraesthesia 28/412 (6.8%) 42 88/408 (21.6%) 191 38/169 (22.5%) 94 42/183 (23%) 165 15/78 (19.2%) 27 9/77 (11.7%) 19
    Peripheral sensory neuropathy 20/412 (4.9%) 42 61/408 (15%) 162 26/169 (15.4%) 91 43/183 (23.5%) 186 9/78 (11.5%) 22 11/77 (14.3%) 48
    Neurology 2/412 (0.5%) 2 10/408 (2.5%) 17 3/169 (1.8%) 4 7/183 (3.8%) 28 1/78 (1.3%) 1 5/77 (6.5%) 20
    Pain 6/412 (1.5%) 7 7/408 (1.7%) 9 1/169 (0.6%) 1 3/183 (1.6%) 4 1/78 (1.3%) 1 5/77 (6.5%) 15
    Psychiatric disorders
    Anxiety 32/412 (7.8%) 63 35/408 (8.6%) 50 19/169 (11.2%) 38 15/183 (8.2%) 35 4/78 (5.1%) 5 8/77 (10.4%) 11
    Depression 47/412 (11.4%) 92 50/408 (12.3%) 100 27/169 (16%) 75 36/183 (19.7%) 132 3/78 (3.8%) 3 10/77 (13%) 33
    Insomnia 42/412 (10.2%) 92 73/408 (17.9%) 150 32/169 (18.9%) 99 23/183 (12.6%) 77 9/78 (11.5%) 12 7/77 (9.1%) 9
    Renal and urinary disorders
    Dysuria 19/412 (4.6%) 25 21/408 (5.1%) 26 6/169 (3.6%) 7 9/183 (4.9%) 11 3/78 (3.8%) 3 5/77 (6.5%) 7
    Pollakiuria 18/412 (4.4%) 32 22/408 (5.4%) 38 7/169 (4.1%) 9 4/183 (2.2%) 4 3/78 (3.8%) 4 3/77 (3.9%) 6
    Stress urinary incontinence 3/412 (0.7%) 6 8/408 (2%) 12 4/169 (2.4%) 13 10/183 (5.5%) 34 0/78 (0%) 0 1/77 (1.3%) 3
    Urinary incontinence 7/412 (1.7%) 13 22/408 (5.4%) 46 9/169 (5.3%) 20 7/183 (3.8%) 24 1/78 (1.3%) 1 3/77 (3.9%) 3
    Respiratory, thoracic and mediastinal disorders
    Cough 37/412 (9%) 57 29/408 (7.1%) 45 22/169 (13%) 49 23/183 (12.6%) 48 10/78 (12.8%) 24 5/77 (6.5%) 21
    Dyspnoea 50/412 (12.1%) 83 67/408 (16.4%) 99 19/169 (11.2%) 40 23/183 (12.6%) 61 11/78 (14.1%) 14 8/77 (10.4%) 9
    Dyspnoea exertional 31/412 (7.5%) 55 20/408 (4.9%) 27 9/169 (5.3%) 20 13/183 (7.1%) 31 4/78 (5.1%) 15 4/77 (5.2%) 8
    Epistaxis 37/412 (9%) 53 13/408 (3.2%) 22 5/169 (3%) 6 0/183 (0%) 0 2/78 (2.6%) 2 0/77 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 94/412 (22.8%) 260 249/408 (61%) 917 102/169 (60.4%) 600 94/183 (51.4%) 469 42/78 (53.8%) 117 49/77 (63.6%) 251
    Hypotrichosis 24/412 (5.8%) 73 9/408 (2.2%) 12 2/169 (1.2%) 2 2/183 (1.1%) 4 0/78 (0%) 0 0/77 (0%) 0
    Pruritus 18/412 (4.4%) 32 20/408 (4.9%) 33 10/169 (5.9%) 18 8/183 (4.4%) 14 2/78 (2.6%) 2 3/77 (3.9%) 3
    Rash 42/412 (10.2%) 59 42/408 (10.3%) 68 30/169 (17.8%) 50 25/183 (13.7%) 48 8/78 (10.3%) 9 8/77 (10.4%) 12
    Vascular disorders
    Flushing 6/412 (1.5%) 9 11/408 (2.7%) 22 10/169 (5.9%) 14 8/183 (4.4%) 34 1/78 (1.3%) 4 1/77 (1.3%) 2
    Hot flush 38/412 (9.2%) 99 60/408 (14.7%) 145 35/169 (20.7%) 132 38/183 (20.8%) 172 11/78 (14.1%) 31 6/77 (7.8%) 22

    Limitations/Caveats

    Trial was designed with overall survival as primary endpoint. Enrollment was slower than expected. After 4 years, 919 patients were randomized and in August 2006, protocol was amended: primary endpoint was changed to progression free survival (PFS).

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Chief Medical Officer
    Organization Eli Lilly and Company
    Phone 800-545-5979
    Email
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00191646
    Other Study ID Numbers:
    • 6891
    • B9E-US-S302
    First Posted:
    Sep 19, 2005
    Last Update Posted:
    Mar 4, 2011
    Last Verified:
    Feb 1, 2011