NCT00565851|Active Not RecruitingPhase 3Results

Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer

A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel (or Gemcitabine) Alone or in Combination With Bevacizumab (NSC #704865) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Peritoneal Primary and Fallopian Tube Cancer. NCI-Supplied Agents: Bevacizumab (NSC #704865)

National Cancer Institute (NCI)ClinicalTrials.gov

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6 other identifiers

NCI-2009-0058709-0205GOG-0213CDR0000546714U10CA027469U10CA180868

Study Type

interventional

Target

1,052

Locations

3 countries

Sites

709

Timeline

RegisteredNov 2007

StartedDec 2007

CompletionJan 2028

Brief Summary

This randomized phase III trial studies carboplatin, paclitaxel and gemcitabine hydrochloride when given together with or without bevacizumab after surgery to see how well it works in treating patients with ovarian, epithelial, primary peritoneal, or fallopian tube cancer that has come back. Drugs used in chemotherapy, such as carboplatin, paclitaxel and gemcitabine hydrochloride work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as bevacizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether combination chemotherapy is more effective when given with or without bevacizumab after surgery in treating patients with ovarian, epithelial, primary peritoneal, or fallopian tube cancer.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

1,052

participants targeted

Target at P75+ for phase_3

Timeline

20mo left

Started Dec 2007

Longer than P75 for phase_3

Geographic Reach

3 countries

709 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

20.1 years study duration

Study Progress92%

Dec 2007Jan 2028

First Submitted

Initial submission to the registry

November 29, 2007

Completed

1 day until next milestone

First Posted

Study publicly available on registry

November 30, 2007

Completed

6 days until next milestone

Study Start

First participant enrolled

December 6, 2007

Completed

11.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 30, 2019

Completed

1.6 years until next milestone

Results Posted

Study results publicly available

December 14, 2020

Completed

7.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2028

Expected

Last Updated

December 30, 2025

Status Verified

December 1, 2025

Enrollment Period

11.4 years

First QC Date

November 29, 2007

Results QC Date

November 13, 2020

Last Update Submit

December 16, 2025

Conditions

Primary Peritoneal Serous Adenocarcinoma Fallopian Tube Mucinous Adenocarcinoma Fallopian Tube Serous Adenocarcinoma Fallopian Tube Transitional Cell Carcinoma Fallopian Tube Undifferentiated Carcinoma Mucinous Adenocarcinoma Ovarian Brenner Tumor Ovarian Clear Cell Adenocarcinofibroma Ovarian Clear Cell Adenocarcinoma Ovarian Endometrioid Adenocarcinoma Ovarian Seromucinous Carcinoma Ovarian Serous Adenocarcinoma Ovarian Transitional Cell Carcinoma Ovarian Undifferentiated Carcinoma Primary Peritoneal Clear Cell Adenocarcinoma Primary Peritoneal Endometrioid Adenocarcinoma Primary Peritoneal Transitional Cell Carcinoma Primary Peritoneal Undifferentiated Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Ovarian Carcinoma Recurrent Primary Peritoneal Carcinoma Undifferentiated Carcinoma Clear Cell Adenocarcinoma Fallopian Tube Clear Cell Adenocarcinoma Fallopian Tube Endometrioid Adenocarcinoma

Outcome Measures

Primary Outcomes (2)

To Determine if Surgical Secondary Cytoreduction in Addition to Adjuvant Chemotherapy Increases the Duration of Overall Survival in Patients With Recurrent Platinum Sensitive Epithelial Ovarian Cancer, Peritoneal Primary or Fallopian Tube Cancer
The treatment regimens will be compared with a logrank procedure which includes all of the patients categorized by their randomly assigned treatment. The logrank test will be stratified by the secondary surgical debulking status (randomized to undergo cytoreduction, vs randomized to not undergo secondary cytoreduction vs not a candidate or did not consent to secondary surgical cytoreduction) and the duration of treatment free-interval prior to enrolling onto this study (6-12 months vs \> 12 months). The median duration of follow-up is calculated by the reverse Kaplan-Meier method.
The time frame is 82.5 months (median duration of follow-up)
To Determine if the Addition of Bevacizumab Increases the Duration of Overall Survival Relative to Second-line Paclitaxel and Carboplatin Alone in Patients With Recurrent Platinum Sensitive Epithelial Ovarian, Peritoneal Primary or Fallopian Tube Cancer
The treatment regimens will be compared with a logrank procedure which includes all of the patients categorized by their randomly assigned treatment. The logrank test will be stratified by the secondary surgical debulking status (randomized to undergo cytoreduction, vs randomized to not undergo secondary cytoreduction vs not a candidate or did not consent to secondary surgical cytoreduction) and the duration of treatment free-interval prior to enrolling onto this study (6-12 months vs \> 12 months). The median duration of follow-up is calculated by the reverse Kaplan-Meier method.
The time frame is 82.5 months (median duration of follow-up).

Secondary Outcomes (7)

Progression-free Survival (Chemotherapy Analysis)
Radiographic assessment of disease was conducted during chemotherapy and then every 6 months during the maintenance / surveillance phase
Progression Free Survival (Surgery Analysis)
Radiographic assessment of disease (in patients with measurable and non-measurable disease) was conducted Every three months for two years and then every 6 months after completion of chemotherapy during the maintenance/surveillance phase.
Summary of Adverse Events (CTCAE Version 4.0)
During treatment period and up to 100 days after stopping the study treatment, a median duration of 82.5 months
Patient Reported Quality of Life (Chemotherapy Analysis)
1. Prior to cycle 1 (baseline), 2. Prior to cycle 3 (6 weeks post cycle 1), 3. Prior to cycle 6 (15 weeks post cycle 1), 4. 6 months post cycle 1, 5. 12 months post cycle 1.
Patient Reported Physical Function (Chemotherapy Analysis)
1. Prior to cycle 1 (baseline), 2. Prior to cycle 3 (6 weeks post cycle 1), 3. Prior to cycle 6 (15 weeks post cycle 1), 4. 6 months post cycle 1, 5. 12 months post cycle 1.
+2 more secondary outcomes

Study Arms (4)

Arm I (paclitaxel, docetaxel, carboplatin)

ACTIVE COMPARATOR

Patients receive paclitaxel IV over 3 hours or docetaxel IV over 1 hour and carboplatin over 30 minutes on day 1. Treatment repeats every 21 days.

Drug: CarboplatinDrug: DocetaxelOther: Laboratory Biomarker AnalysisDrug: PaclitaxelOther: Quality-of-Life Assessment

Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab)

EXPERIMENTAL

Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days.

Biological: BevacizumabDrug: CarboplatinDrug: DocetaxelOther: Laboratory Biomarker AnalysisDrug: PaclitaxelOther: Quality-of-Life Assessment

Arm III (gemcitabine hydrochloride, carboplatin)

EXPERIMENTAL

Patients receive gemcitabine hydrochloride IV over 60 minutes on days 1 and 8 and carboplatin as in Arm I.

Drug: CarboplatinDrug: Gemcitabine HydrochlorideOther: Laboratory Biomarker AnalysisOther: Quality-of-Life Assessment

Arm IV (gemcitabine hydrochloride, bevacizumab, carboplatin)

EXPERIMENTAL

Patients receive gemcitabine hydrochloride IV as in Arm III, bevacizumab IV and carboplatin IV as in Arm II.

Biological: BevacizumabDrug: CarboplatinDrug: Gemcitabine HydrochlorideOther: Laboratory Biomarker AnalysisOther: Quality-of-Life Assessment

Interventions

BevacizumabBIOLOGICAL

Given IV

Also known as: ABP 215, ABP-215, ABP215, Alymsys, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Avzivi, Aybintio, BAT 1706, BAT-1706, BAT1706, BAT1706 Biosimilar, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BAT1706, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MB02, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar QL1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-adcd, Bevacizumab-awwb, Bevacizumab-aybi, Bevacizumab-bvzr, Bevacizumab-equi, Bevacizumab-maly, Bevacizumab-onbe, Bevacizumab-tnjn, BP102, BP102 Biosimilar, CT P16, CT-P16, CTP16, Equidacent, FKB 238, FKB-238, FKB238, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, MB 02, MB-02, MB02, Mvasi, MYL-1402O, Onbevzi, Oyavas, PF 06439535, PF-06439535, PF06439535, QL1101, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Vegzelma, Zirabev

Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab)Arm IV (gemcitabine hydrochloride, bevacizumab, carboplatin)

CarboplatinDRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Arm I (paclitaxel, docetaxel, carboplatin)Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab)Arm III (gemcitabine hydrochloride, carboplatin)Arm IV (gemcitabine hydrochloride, bevacizumab, carboplatin)

DocetaxelDRUG

Given IV

Also known as: Docecad, RP 56976, RP-56976, RP56976, Taxotere, Taxotere Injection Concentrate

Arm I (paclitaxel, docetaxel, carboplatin)Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab)

Gemcitabine HydrochlorideDRUG

Given IV

Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

Arm III (gemcitabine hydrochloride, carboplatin)Arm IV (gemcitabine hydrochloride, bevacizumab, carboplatin)

Laboratory Biomarker AnalysisOTHER

Correlative studies

PaclitaxelDRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Arm I (paclitaxel, docetaxel, carboplatin)Arm II (paclitaxel, docetaxel, carboplatin, bevacizumab)

Quality-of-Life AssessmentOTHER

Ancillary studies

Also known as: Quality of Life Assessment

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Patients enrolled after August 28, 2011 must be candidates for cytoreductive surgery and consent to have their surgical treatment determined by randomization
Patients must have histologic diagnosis of epithelial ovarian carcinoma, peritoneal primary or fallopian tube carcinoma, which is now recurrent
Patients with the following histologic epithelial cell types are eligible: serous adenocarcinoma, endometrioid adenocarcinoma, mucinous adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, transitional cell carcinoma, malignant Brenner's tumor, or adenocarcinoma not otherwise specified (N.O.S.)
Patients must have had a complete response to front-line platinum-taxane therapy (at least three cycles)
A complete response to front-line chemotherapy must include: negative physical exam, negative pelvic exam and normalization of CA125, if elevated at baseline; although not required, any radiographic assessment of disease status (e.g. CT, magnetic resonance imaging \[MRI\], positron emission tomography \[PET\]/CT, etc) obtained following the completion of primary therapy should be considered negative for disease
All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e. bevacizumab)
Front-line treatment may include maintenance therapy following complete clinical or pathological response; however, maintenance cytotoxic chemotherapy must be discontinued for a minimum of 6 months prior to documentation of recurrent disease; patients receiving maintenance biological therapy or hormonal therapy are ELIGIBLE provided their recurrence is documented more than 6 months from primary cytotoxic chemotherapy completion (includes maintenance chemotherapy) AND a minimum 4 weeks has elapsed since their last infusion of biological therapy
Patients must have clinically evident recurrent disease for the purpose of this study
Measurable disease (Response Evaluation Criteria in Solid Tumors \[RECIST\]) is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each lesion must be more than or equal to 20 mm when measured by conventional techniques, MRI or CT, or more than or equal to 10 mm when measured by spiral CT
Absolute neutrophil count (ANC) greater than or equal to 1,500/mm\^3, equivalent to Common Toxicity Criteria for Adverse Events version (v)4.0 (CTCAE) grade 1
Platelets greater than or equal to 100,000/mm\^3 (CTCAE grade 0-1)
Creatinine (non-isotope dilution mass spectrometry \[IDMS\]) =\< 1.5 x institutional upper limit normal (ULN), CTCAE grade 1
Total bilirubin =\< 1.5 ULN (CTCAE grade 1)
Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) =\< 2.5 times the upper limit of normal in the absence of liver metastasis; SGOT/AST \< 5.0 times ULN in the presence of liver metastasis
Alkaline phosphatase =\< 2.5 times the upper limit of normal in the absence of liver metastasis; alkaline phosphatase \< 5.0 times ULN in the presence of liver metastasis
+5 more criteria

You may not qualify if:

Patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen)
Patients receiving concurrent immunotherapy, or radiotherapy
Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis are excluded
Patients whom have already undergone secondary cytoreduction for recurrent disease are excluded
Patients with a prior histologic diagnosis of borderline, low malignant potential (grade 0) epithelial carcinoma that was surgically resected and who subsequently developed an unrelated, new invasive epithelial ovarian or peritoneal primary cancer are eligible provided that they meet the criteria listed above
Patients who require parenteral hydration or nutrition and have evidence of partial bowel obstruction or perforation
Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other than ovarian, fallopian tube, and primary peritoneal) are excluded
Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, are excluded, unless all of the following conditions are met: stage not greater than I-B; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other International Federation of Gynecology and Obstetrics (FIGO) grade 3 lesions
Patients with uncontrolled infection
Patients with concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
Patients with \>= grade 2 peripheral neuropathy
Patients with a history of allergic reactions to carboplatin and/or paclitaxel or chemically similar compounds; patients with allergic (hypersensitivity) reactions to these chemotherapeutic agents are NOT excluded IF they were successfully retreated following a desensitization program or protocol
This criterion applies only to the patients enrolled before August 29, 2011 and those enrolled after this date electing to receive bevacizumab; patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
Patients of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are nursing are not eligible for this trial; to date, no fetal studies in animal or humans have been performed; the possibility of harm to a fetus is likely; bevacizumab specifically inhibits VEGF, which is responsible for the formation of new blood vessels during development, and antibodies can cross the placenta; therefore, bevacizumab should not be administered to pregnant women; in addition, there are unknown immediate and long-term consequences of chemotherapy administration to these women; in addition, surgical exploration as mandated by randomization during pregnancy may cause imminent mortal consequences; further, it is not known whether bevacizumab is excreted in human milk; because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women; subjects will be apprised of the large potential risk to a developing fetus
Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, 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
+13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead
NRG Oncologycollaborator

Study Sites (709)

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC