Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Laryngeal Diseases

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Laryngeal Cancer

Hypopharyngeal Cancer

Pharmaceutical Solutions

All Drugs and Chemicals

Antineoplastic Agents

Natriuretic Agents

Antiemetics

Gastrointestinal Agents

Emetics

Amino Acids

Cisplatin

Mannitol

Arginine

Histidine

Ficlatuzumab will be administered as an IV infusion over 30-60 minutes, once every two weeks beginning the week prior to cisplatin-IMRT (week -1), for a total of 4 doses.

Cisplatin will be administered as an IV infusion over 60 minutes on Monday, Tuesday, or Wednesday of each treatment week beginning concurrent with IMRT during week 1 of study treatment (and one week following the first dose of ficlatuzumab) for a total of 7 doses.

IMRT: Treatment will be delivered once daily, 5 fractions per week, 35 - 37 fractions, no weekends or holidays over 7 - 8 weeks. All targets will be treated sequentially.

Ficlatuzumab Concentrate for Injection, 20 mg/mL, is formulated in 10 mM histidine buffer pH 5.8. The formulation also includes 142 mM arginine (for isotonicity) and 0.01% polysorbate 80. The product is sterile filtered and aseptically filled into washed and depyrogenated 5 mL glass vials.The product is a clear to slightly opalescent, colorless to slightly yellow, solution.

Ficlatuzumab Concentrate for Injection is to be administered by IV infusion as an admixture with normal saline solution. The admixture solution in an IV bag is connected to an infusion set containing a 0.22 µm low protein-binding in line filter. The filtered admixture solution is clear to slightly opalescent.

Ficlatuzumab is to be stored under refrigerated conditions (2C - 8C)

Ficlatuzumab

Each vial contains 10 mg of DDP, 19 mg of sodium chloride, 100 mg of mannitol, and hydrochloric acid for pH adjustment. One vial is reconstituted with 10 ml of sterile water. The pH range will be 3.5 to 4.5.

Cisplatin will be given as a bolus, infused over 1-2 hours along with appropriate hydration and anti-emetics.

Reconstituted solution of cisplatin is stable for 20 hours when stored at 27°C and should be protected from light if not used within 6 hours. The vials and injection should not be refrigerated. Cisplatin has been shown to react with aluminum needles, producing a black precipitate within 30 minutes.

Immobilization should be performed to ensure daily reproducibility of setup.Treatment planning CT scans will be required to define tumor, clinical and planning target volumes.The treatment planning CT scan should be performed with IV contrast. All tissues to be irradiated must be included in the CT scan.

Targets are defined as primary (requiring a higher dose) and secondary (targets at lower risk requiring a lower dose). The primary target is the PTV3 of the primary tumor and lymph nodes containing clinical or radiographic evidence of metastases. The secondary target is the PTVs consist of an area at intermediate risk (PTV2) and that containing the lowest risk of lymph node involvement (PTV2).

The treatment plan will be based on an analysis of the volumetric dose, including dose volume histogram (DVH) analyses of the PTV and critical normal structures. Inverse planning will be utilized to deliver optimal dose to the PTVs while excluding noninvolved normal tissue.

Intensity Modulated Radiotherapy (IMRT)

Julie E Bauman, MD, MPH

Head and neck squamous cell carcinoma (HNSCC) is the most common cancer arising in the upper aerodigestive tract, and is the sixth leading incident cancer worldwide. Despite advances in multimodality therapy, 5-year overall survival (OS) is 40-60%, and has increased only incrementally in the past two decades. The current standard of care for primary nonsurgical management of locally advanced HNSCC is concurrent cisplatin-radiotheray, which significantly improved OS, progression-free survival, and locoregional control compared with radiotherapy alone in the landmark Intergroup trial 0126.

The MET proto-oncogene encodes c-Met, a heterodimeric growth factor receptor bound exclusively by its ligand, hepatocyte growth factor (HGF). In the laboratory, activation of the HGF/c-Met pathway is associated with resistance to cisplatin and radiotherapy in HNSCC. We hypothesize that the addition of an HGF/c-Met pathway inhibitor to cisplatin-radiotherapy may improve outcomes in HNSCC. Ficlatuzumab (AV-299) is a humanized HGF-inhibitory IgG1 monoclonal antibody.

The primary objective of this study is to establish the recommended phase II dose (RP2D) of the combination of ficlatuzumab, cisplatin and intensity-modulated radiotherapy (IMRT), in patients with locally advanced HNSCC. The dose-finding study design will follow a Narayana k-in-a-row design with k set to 3 to target a 33% DLT rate. In the dose-finding phase, a total of either 10 or 14 patients will be treated. If no DLTs are observed among 10 patients, the highest dose tier will be declared the RP2D. Otherwise the RP2D will be estimated from DLTs across all dose levels by isotonic regression. The secondary objective is to estimate biomarker association with preliminary clinical response. We will evaluate biomarkers of HGF/cMet pathway activation in tumor tissue, plasma, and immune cells.

This will be a phase Ib trial where ficlatuzumab will be added to the standard of care for locally advanced HNSCC: cisplatin-IMRT. Biomarkers of HGF/cMet pathway activation that may associate with clinical response will be developed in an expansion cohort. Patients with high or intermediate risk, locally advanced HNSCC will be eligible.

A diagnostic primary tumor block for biomarker correlatives is mandatory for inclusion to this study. A representative paraffin block of the original diagnosis and all repeat biopsies, if available, will be submitted.

The starting dose of ficlatuzumab (dose tier 1) will be 10 mg/kg every 2 weeks, beginning the week prior to cisplatin-IMRT (week -1). Ficlatuzumab will be administered as an IV infusion over 30-60 minutes, for a total of 4 doses.

The starting dose of cisplatin (dose tier 1) will be 40 mg/m2 weekly, beginning concurrent with IMRT during week 1 of study treatment (and one week following the first dose of ficlatuzumab which is administered during week -1 of study treatment). Patients will receive cisplatin once weekly as an IV infusion over 60 minutes, for a total of 7 doses.

Megavoltage energy photon beam irradiation is required. Any treatment planning and delivery system that has been credentialed for head and neck IMRT is acceptable. Immobilization should be performed with a thermoplastic mask to ensure daily reproducibility of setup. Treatment planning CT scans will be required to define tumor, clinical and planning target volumes.The treatment planning CT scan should be acquired with the patient in the same position and immobilization device as for treatment and performed with IV contrast so that major vessels of the neck are easily visualized.

Four dose tiers will be considered for the phase I portion for ficlatuzumab and cisplatin. IMRT will remain consistent for all dose tiers. Under this schema, more than one patient can be enrolled at the same time. However de novo dose escalation cannot occur until 2 patients have completed study treatment without DLT. In the dose-finding phase, a total of 10 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs. If no DLTs are observed among the first 10 patients the recommended for phase 2 dose (RP2D) will be set to dose tier 3. If a DLT is observed and 14 patients are treated and observed, the RP2D will be estimated from DLTs across all dose levels by isotonic regression. The observation period for identifying a DLT will be 10 weeks, or 2 weeks following completion of IMRT, whichever comes later. To be considered a DLT, the toxicity must be at least possibly related to ficlatuzumab. An expansion cohort will then proceed at RP2D until 12 patients have been treated at that dose level.

In the absence of treatment delays due to adverse event(s), treatment may continue until one of the following criteria applies:

* Completion of treatment,
* Disease progression,
* Intercurrent illness that prevents further administration of treatment,
* Unacceptable adverse event(s),
* Patient decides to withdraw from the study, or
* General or specific changes in the patient's condition render the patient unacceptable for further treatment in the judgment of the investigator.

After completing treatment, patients will be followed every 3 months for 2 years, then every 6 months for 3 years, for a total of 5 years from completion of IMRT. Patients removed from study for unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event.

Ficlatuzumab, Cisplatin and IMRT in Locally Advanced Head and Neck Squamous Cell Carcinoma

A Phase 1b Study of Ficlatuzumab, Cisplatin and Intensity Modulated Radiotherapy (IMRT) in Intermediate or High Risk, Previously Untreated, Locally Advanced Head and Neck Squamous Cell Carcinoma With Biomarker Correlatives

A dose escalation/de-escalation plan will be conducted according to an adaptive Narayana k-in-a-row design.We will select the dose of ficlatuzumab that is close to but does not exceed a 33% dose limiting toxicity (DLT) rate when administered with a fixed standard dose of cisplatin and IMRT. The observation period for identifying a DLT will be 10 weeks, or 2 weeks following completion of IMRT, whichever comes later. Note: to be considered a DLT, the toxicity must be at least possibly related to ficlatuzumab.In the dose-finding phase, a total of 10 patients will be treated if no DLTs are observed or 14 patients if at least one DLT occurs. If no DLTs are observed among the first 10 patients the recommended for phase 2 dose (RP2D) will be set to dose tier 3. If a DLT is observed and 14 patients are treated and observed, the RP2D will be estimated from DLTs across all dose levels by isotonic regression.

The preliminary clinical efficacy of the combination of ficlatuzumab, cisplatin and IMRT will be described according to CR rate (RECIST 1.1 and Integrated PET/CT criteria), median TTP, LRC, and median OS in: 1) the entire study population; 2) patients treated at RP2D.

All patients will be evaluable for toxicity from the time of their first treatment with ficlatuzumab. The proportion of DLTs in each dosing cohort will be reported, as will the proportion of AEs in accordance with NCI CTCAE v.4 grading criteria

Submission of primary tumor tissue for biomarker correlatives is mandatory to measure tumor protein levels of cMet and HGF prior to study treatment.

The relationship of percent change in the baseline sum diameter of all measurable RECIST lesions to baseline cMet and HGF will be characterized by a linear, or if necessary, generalized linear or nonlinear regression model with appropriate confidence intervals.

Biomarkers in blood will be quantitatively measured and will be evaluated as predictors of tumor response in appropriate generalized linear models. Calculated p values for testing the significance of the prediction models will be adjusted for false discovery by the method of Benjamini and Hochberg.

The peripheral biomarkers related to HGF/c-Met pathway activation will be evaluated. Baseline values and changes in these biomarkers to quantitative response data and PFS will be evaluated. Biomarkers in tumor and blood will be quantitatively measured and will be evaluated as predictors of tumor response in appropriate generalized linear models. Calculated p values for testing the significance of the prediction models will be adjusted for false discovery by the method of Benjamini and Hochberg.

HNSCC is an immunosuppressive disease. Patients demonstrate lower absolute lymphocyte counts than healthy subjects, impaired natural killer (NK) cell activity and poor antigen-presenting function. Mechanistically, HGF inhibits dendritic cell activation. Evaluation of the dendritic cell and T cell phenotypes in baseline biopsies will be evaluated. In addition, longitudinal T cell and NK cell phenotypes in peripheral blood will be analyzed before, during and after exposure to ficlatuzumab.

HNSCC is an immunosuppressive disease. Patients demonstrate lower absolute lymphocyte counts than healthy subjects, impaired natural killer (NK) cell activity and poor antigen-presenting function. Mechanistically, HGF inhibits dendritic cell activation. Evaluation of the dendritic cell and T cell phenotypes in baseline biopsies will be evaluated. In addition, longitudinal T cell and NK cell phenotypes in peripheral blood will be analyzed before, during and after exposure to ficlatuzumab

AVEO Pharmaceuticals, Inc.

Julie E. Bauman, MD, MPH

Director of the Head and Neck Cancer Section and Thyroid Cancer Section in the Division of Hematology-Oncology at the University of Pittsburgh School of Medicine

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Immune System Diseases

Skin and Connective Tissue Diseases

Recurrence

Adenocarcinoma

Carcinoma, Transitional Cell

Neoplasm Metastasis

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Hypersensitivity

Cystadenocarcinoma, Serous

Adenocarcinoma, Clear Cell

Adenocarcinoma, Mucinous

Cystadenocarcinoma

Brenner Tumor

Fallopian Tube Neoplasms

Carcinoma, Endometrioid

Disease Attributes

Genital Neoplasms, Female

Urogenital Neoplasms

Fallopian Tube Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Ovarian Diseases

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Cystic, Mucinous, and Serous

Endometrial Neoplasms

Uterine Neoplasms

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Ovarian Cancer

Transitional Cell Carcinoma

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Adenocarcinoma of the Appendix

Brenner Tumor of Ovary

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Bevacizumab

Carboplatin

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immunoglobulin G

Endothelial Growth Factors

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Tubulin Modulators

Antimitotic Agents

Angiogenesis Inhibitors

Growth Inhibitors

Immunologic Factors

Antimetabolites

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.

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

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

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

Gemcitabine Hydrochloride

Laboratory Biomarker Analysis

Quality-of-Life Assessment

Robert L Coleman

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.

PRIMARY OBJECTIVES:

I. 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.

II. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases the duration of overall survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer.

SECONDARY OBJECTIVES:

I. To determine if the addition of bevacizumab to the second-line and maintenance phase of treatment increases the duration of progression-free survival relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer.

II. To prospectively determine the incidence of carboplatin and paclitaxel hypersensitivity in these patients undergoing retreatment with both agents as first recurrence therapy.

III. To determine if surgical secondary cytoreduction in addition to adjuvant chemotherapy increases quality of life (QOL) in patients with recurrent platinum-sensitive epithelial ovarian cancer, peritoneal primary or fallopian tube cancer, as measured by the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) trial outcome index and Rand Short Form (SF)-36 physical functioning scale.

IV. To determine if the addition of bevacizumab to the second-line and maintenance phases of treatment increases QOL relative to second-line paclitaxel and carboplatin alone in patients with recurrent platinum-sensitive epithelial ovarian, peritoneal primary or fallopian tube cancer.

TRANSLATIONAL RESEARCH OBJECTIVES:

I. To define molecular and biochemical profiles associated with the duration of progression-free survival in platinum-sensitive recurrent ovarian, peritoneal primary or fallopian tube carcinoma treated with combination chemotherapy with or without bevacizumab followed with or without maintenance bevacizumab therapy in the presence or absence of secondary surgical cytoreduction.

II. To identify molecular determinants that predict sensitivity or resistance to carboplatin and paclitaxel with or without bevacizumab followed with or without maintenance bevacizumab therapy.

III. To bank deoxyribonucleic acid (DNA) from whole blood for research and evaluate the association between single nucleotide polymorphisms (SNPs) and measures of clinical outcome including overall survival, progression-free survival and adverse events.

OUTLINE: Patients are assigned to 1 of 4 treatment groups. Patients who are not candidates for surgical cytoreduction (i.e., those for whom complete cytoreduction in the estimation of the investigator is impossible or a medical infirmity precludes exploration and debulking) are eligible to receive chemotherapy after randomization.

Patients who are eligible for surgery undergo abdominal exploration with cytoreduction. Patients are then randomized to 1 of 4 treatment arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 3 hours or docetaxel IV over 1 hour and carboplatin IV over 60 minutes on day 1.

ARM II: Patients receive chemotherapy as in Arm I and bevacizumab IV over 30-90 minutes on day 1.

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

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

In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with measurable disease achieving a clinical response (CR) receive 6-8 courses of therapy. Patients with stable disease or partial regression receive a maximum of 8 courses.

Patients without measurable lesions as determined by a computed tomography (CT) scan prior to initiating study treatment continue therapy for 6 courses or, if cancer antigen (CA)-125 normalizes, for 2 courses beyond CA-125 normalization, whichever is greater. Patients in Arm II then receive a maintenance regimen comprising bevacizumab IV over 30-90 minutes. Treatment with bevacizumab alone repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then yearly for 5 years.

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)

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.

Progression-free survival was defined as the time from randomization to cancer progression as shown on radiography, according to the RECIST version 1.0 criteria, an increase in the CA125 level according to Gynecologic Cancer InterGroup (GCIG) criteria, global deterioration of health, or death from any cause.

Number of treated patients with at least one adverse event reported (assessed by Common Terminology Criteria for Adverse Events (version 4.0))

Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for ovarian cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). The FACT-O TOI score ranges 0-100 with a large score suggests better QOL.

Patient reported physical functioning was measured with physical functioning subscale of the RAND SF-36. The Physical Functioning Subscale consists of 10 items concerning activities of daily living: walking, climbing stairs, bathing, dressing, and performance of physical activities. Each item is rated on a three-point scale of limitation of activity due to the patients' health from 1=limited a lot to 3=not limited. The total PF score is the summation of item scores and then rescaled to 0-100. A larger score suggests better physical functioning.

Patient reported physical functioning was measured with physical functioning subscale of the RAND SF-36. The Physical Functioning subscale consists of 10 items concerning activities of daily living: walking, climbing stairs, bathing, dressing, and performance of physical activities. Each item is rated on a three-point scale of limitation of activity due to the patients' health from 1=limited a lot to 3=not limited. The total PF score is the summation of item scores and then rescaled to 0-100. A larger score suggests better physical functioning. This measure was completed by US patients only.

NRG Oncology

National Cancer Institute (NCI)

Eligible and treated participants were affected if they experienced grade 1 - 5 adverse event. Adverse events were not collected in a manner that allow them to be attributed to an intervention (i.e. surgery or chemotherapy).

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. Patients are not in secondary cytoreductive surgery portion of study.

Arm I (no Surgery; Carboplatin and Paclitaxel)

Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days. Patients are not in secondary cytoreductive surgery portion of study.

Arm II (no Surgery; Carboplatin, Paclitaxel and Bevacizumab)

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. Patients receive secondary cytoreductive surgery.

Arm III (Surgery; Carboplatin and Paclitaxel)

Arm IV (Surgery; Carboplatin, Paclitaxel and Bevacizumab)

Patients receive carboplatin as in arm I. Patients receive gemcitabine. Treatment repeats every 21 days. Patients do not receive secondary cytoreductive surgery.

Arm V (no Surgery; Carboplatin and Gemcitabine)

Patients receive carboplatin as in arm I and bevacizumab IV over 30-90 minutes on day 1. Patients receive gemcitabine. Treatment repeats every 21 days. Patients do not receive secondary cytoreductive surgery.

Arm VI (no Surgery; Carboplatin, Gemcitabine and Bevacizumab)

Patients receive carboplatin as in arm I. Patients receive gemcitabine. Treatment repeats every 21 days. Patients receive secondary cytoreductive surgery.

Arm VII (Surgery; Carboplatin and Gemcitabine)

Patients receive carboplatin as in arm I and bevacizumab IV over 30-90 minutes on day 1. Patients receive gemcitabine. Treatment repeats every 21 days. Patients receive secondary cytoreductive surgery.

Arm VIII (Surgery; Carboplatin, Gemcitabine and Bevacizumab)

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. Patients are not in secondary cytoreductive surgery portion of study.

Carboplatin: Given IV

Docetaxel: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Quality-of-Life Assessment: Ancillary studies

Patients receive chemotherapy as in arm I and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days. Patients are not in secondary cytoreductive surgery portion of study.

Bevacizumab: Given IV

Carboplatin: Given IV

Docetaxel: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Quality-of-Life Assessment: Ancillary studies

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. Patients receive secondary cytoreductive surgery.

Carboplatin: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Quality-of-Life Assessment: Ancillary studies

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. Patients receive secondary cytoreductive surgery.

Bevacizumab: Given IV

Carboplatin: Given IV

Docetaxel: Given IV

Laboratory Biomarker Analysis: Correlative studies

Paclitaxel: Given IV

Quality-of-Life Assessment: Ancillary studies

Patients receive carboplatin as in arm I. Patients receive gemcitabine. Treatment repeats every 21 days. Patients do not receive secondary cytoreductive surgery.

Carboplatin: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Patients receive carboplatin as in arm I and bevacizumab IV over 30-90 minutes on day 1. Patients receive gemcitabine. Treatment repeats every 21 days. Patients do not receive secondary cytoreductive surgery.

Bevacizumab: Given IV

Carboplatin: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Arm VI (no Surgery; Carboplatin, Gemcitabine and Bevacizumab))

Patients receive carboplatin as in arm I. Patients receive gemcitabine. Treatment repeats every 21 days. Patients receive secondary cytoreductive surgery.

Carboplatin: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Patients receive carboplatin as in arm I and bevacizumab IV over 30-90 minutes on day 1. Patients receive gemcitabine. Treatment repeats every 21 days. Patients receive secondary cytoreductive surgery.

Bevacizumab: Given IV

Carboplatin: Given IV

Gemcitabine Hydrochloride: Given IV

Laboratory Biomarker Analysis: Correlative studies

Quality-of-Life Assessment: Ancillary studies

Arm VIII (Surgery; Carboplatin, Gemcitabine and Bevacizumab))

Total

Age, Continuous

< 40 years

40 - 49 years

50 - 59 years

60 - 69 years

70 - 79 years

≥ 80 years

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

South Korea

United States

Japan

Russia

Region of Enrollment

Serous

Endometrioid

Clear Cell

Mucinous

Other

Histology

Christopher Purdy on behalf of Austin Miller PhD

All patients enrolled in the study who did not receive cytoreductive surgery and included in the surgery analysis

No Cytoreductive Surgery

All patients enrolled in the study who received secondary cytoreductive surgery and were included in the surgery analysis

Cytoreductive Surgery

All patients who were eligible for the surgery analysis (data were combined and analyzed according to randomized surgical assignment, regardless of chemotherapy regimen, as pre-specified in the study protocol)

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

All patients who received paclitaxel and carboplatin chemotherapy and were included in the chemotherapy analysis

Paclitaxel and Carboplatin Chemotherapy

All patients who received paclitaxel and carboplatin chemotherapy with bevacizumab followed by bevacizumab maintenance therapy and were included in the chemotherapy analysis

Paclitaxel and Carboplatin Chemotherapy With Bevacizumab

All patients who were enrolled between December 10, 2007 and August 26, 2011 and received paclitaxel and carboplatin (with or without bevacizumab) (data were combined and analyzed according to randomized chemotherapy regimen, regardless of surgical assignment, as pre-specified in the study protocol).

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

All patients who were enrolled and eligible for the chemotherapy analysis (data were combined and analyzed according to randomized chemotherapy regimen, regardless of surgical assignment, as pre-specified in the study protocol).

Progression-free Survival (Chemotherapy Analysis)

All randomized patients who were eligible for the surgery analysis (data were combined and analyzed according to randomized surgical assignment, regardless of chemotherapy regimen, as pre-specified in the study protocol).

Progression Free Survival (Surgery Analysis)

Summary of Adverse Events (CTCAE Version 4.0)

Prior to cycle 1 (baseline)

Provided baseline and at least one follow-up assessment (data were combined and analyzed according to randomized chemotherapy regimen, regardless of surgical assignment, as pre-specified in the study protocol).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Ficlatuzumab, Cisplatin and IMRT in Locally Advanced Head and Neck Squamous Cell Carcinoma	NCT02277184	Carcinoma, Squa...	Ficlatuzumab Cisplatin Intensity Modul...	18 Years -	University of Pittsburgh
Carboplatin, Paclitaxel and Gemcitabine Hydrochloride With or Without Bevacizumab After Surgery in Treating Patients With Recurrent Ovarian, Epithelial, Primary Peritoneal, or Fallopian Tube Cancer	NCT00565851	Clear Cell Aden... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Fallopian Tube ... Mucinous Adenoc... Ovarian Brenner... Ovarian Clear C... Ovarian Clear C... Ovarian Endomet... Ovarian Seromuc... Ovarian Serous ... Ovarian Transit... Ovarian Undiffe... Primary Periton... Primary Periton... Primary Periton... Primary Periton... Primary Periton... Recurrent Fallo... Recurrent Ovari... Recurrent Prima... Undifferentiate...	Bevacizumab Carboplatin Docetaxel Gemcitabine Hyd... Laboratory Biom... Paclitaxel Quality-of-Life...	18 Years -	National Cancer Institute (NCI)
Ficlatuzumab, Cisplatin and IMRT in Locally Advanced Head and Neck Squamous Cell Carcinoma	NCT02277184	Carcinoma, Squa...	Ficlatuzumab Cisplatin Intensity Modul...	18 Years -	University of Pittsburgh
Panitumumab Chemoradiotherapy Chemotherapy for Squamous Cancer of the Head and Neck	NCT00513383	Squamous Cell C...	Panitumumab Carboplatin Paclitaxel Intensity Modul... 5-Fluorouracil Docetaxel Cisplatin	18 Years -	Massachusetts General Hospital

Spots Global Cancer Trial Database for undifferentiated carcinoma