NCT01074411

Brief Summary

This phase I trial studies the side effects and best dose of intraperitoneal bortezomib when given together with intraperitoneal carboplatin in treating patients with ovarian epithelial cancer, fallopian tube cancer, or primary peritoneal cancer that is persistent or has come back. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, 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. Bortezomib may help carboplatin work better by making tumor cells more sensitive to the drug. Infusing bortezomib and carboplatin directly into the abdomen (intraperitoneal) may kill more tumor cells.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
33

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Apr 2010

Longer than P75 for phase_1

Geographic Reach
1 country

14 active sites

Status
completed

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

First Submitted

Initial submission to the registry

February 23, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 24, 2010

Completed
1 month until next milestone

Study Start

First participant enrolled

April 5, 2010

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 4, 2014

Completed
3.8 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 27, 2018

Completed
Last Updated

August 9, 2019

Status Verified

August 1, 2019

Enrollment Period

4 years

First QC Date

February 23, 2010

Last Update Submit

August 8, 2019

Conditions

Outcome Measures

Primary Outcomes (2)

  • Dose-limiting toxicities defined by drug-related adverse events which occur in association with the first course of treatment as evaluated by the NCI CTCAE version 4 unless clearly unrelated to study drugs (e.g., disease progression)

    21 days

  • Frequency and severity of toxicities as assessed by NCI CTCAE version 4

    Up to 1 year

Secondary Outcomes (3)

  • Objective tumor response (complete and partial response)

    Up to 1 year

  • Progression free survival

    Time from study entry to time of progression or death, whichever occurs first, assessed up to 1 year

  • Pharmacokinetic parameters

    10 minutes prior to infusion; immediately following infusion; 15, 30 and 60 minutes after infusion; immediately following carboplatin; 90 minutes after infusion; and 2, 4, and 6 hours after infusion

Study Arms (1)

Treatment (bortezomib, carboplatin)

EXPERIMENTAL

Patients receive bortezomib IP and carboplatin IP on day 1. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: BortezomibDrug: CarboplatinOther: Laboratory Biomarker AnalysisOther: Pharmacological Study

Interventions

Given IP

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, Velcade
Treatment (bortezomib, carboplatin)

Given IP

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo
Treatment (bortezomib, carboplatin)

Correlative studies

Treatment (bortezomib, carboplatin)

Correlative studies

Treatment (bortezomib, carboplatin)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must have recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer; histologic documentation of the original primary tumor is required via the pathology report
  • 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 either measurable disease or detectable disease:
  • Measurable disease will be defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; measureable disease 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 \>= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or \>= 20 mm when measured by chest x-ray; lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI
  • Detectable disease is defined in a patient as one who does not have measurable disease but has at least one of the following conditions:
  • Baseline values of cancer antigen (CA)-125 at least twice the upper limit of normal
  • Ascites and/or pleural effusion attributed to tumor
  • Solid and/or cystic abnormalities on radiographic imaging that do not meet RECIST 1.1 definitions for target lesions
  • In addition, patients are allowed to undergo surgical cytoreduction of relapsed disease as proof of detectable disease at the discretion of their treating physician; if performed to allow participation in this protocol, the operative and pathology reports will be required for submission
  • Patients must have a Gynecologic Oncology Group (GOG) performance status 0, 1, or 2
  • Recovery from effects of recent surgery, radiotherapy, or chemotherapy
  • Patients should be free of active infection requiring antibiotics (with the exception of uncomplicated urinary tract infection \[UTI\])
  • Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to registration; continuation of hormone replacement therapy is permitted
  • Any other prior therapy directed at the malignant tumor, including biological and immunologic agents, must be discontinued at least three weeks prior to registration
  • Patients must have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound; this initial treatment may have included non-cytotoxic therapy, intraperitoneal therapy, consolidation, or extended therapy administered after surgical or non-surgical assessment
  • +15 more criteria

You may not qualify if:

  • Patients who have had prior therapy with bortezomib
  • Patient with a history of other invasive malignancies, with the exceptions of non-melanoma skin cancer and localized breast cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
  • Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian cancer are excluded; prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than three years prior to registration, and the patient remains free of recurrent or metastatic disease
  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian cancer are excluded
  • Patients may have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
  • Patients with known brain metastases are excluded
  • History of allergic reactions attributed to carboplatin or compounds of similar chemical or biologic composition to bortezomib including boron or mannitol
  • 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 a history of prior myocardial infarction in the last 12 months or patients with new electrocardiographic evidence of acute ischemia or new conduction abnormalities are ineligible
  • Uncontrolled concurrent illness including but not limited to ongoing or active infection that requires parenteral antibiotics, acute hepatitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with insulin-dependent diabetes will be excluded
  • Concomitant medications known to inhibit or induce cytochrome P450, family 3, subfamily A, polypeptide 4 (3A4) are to be avoided

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Hartford Hospital

Hartford, Connecticut, 06102, United States

Location

The Hospital of Central Connecticut

New Britain, Connecticut, 06050, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Cooper Hospital University Medical Center

Camden, New Jersey, 08103, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Cancer Center/Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Hillcrest Hospital Cancer Center

Mayfield Heights, Ohio, 44124, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

Location

Women and Infants Hospital

Providence, Rhode Island, 02905, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

  • Jandial DA, Brady WE, Howell SB, Lankes HA, Schilder RJ, Beumer JH, Christner SM, Strychor S, Powell MA, Hagemann AR, Moore KN, Walker JL, DiSilvestro PA, Duska LR, Fracasso PM, Dizon DS. A phase I pharmacokinetic study of intraperitoneal bortezomib and carboplatin in patients with persistent or recurrent ovarian cancer: An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol. 2017 May;145(2):236-242. doi: 10.1016/j.ygyno.2017.03.013. Epub 2017 Mar 22.

MeSH Terms

Conditions

Brenner TumorFallopian Tube NeoplasmsOvarian Neoplasms

Interventions

BortezomibCarboplatin

Condition Hierarchy (Ancestors)

Neoplasms, FibroepithelialNeoplasms, Fibrous TissueNeoplasms, Connective TissueNeoplasms, Connective and Soft TissueNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesGonadal DisordersEndocrine System DiseasesNeoplasms by SiteFallopian Tube DiseasesEndocrine Gland Neoplasms

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsCoordination Complexes

Study Officials

  • Don Dizon

    NRG Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 23, 2010

First Posted

February 24, 2010

Study Start

April 5, 2010

Primary Completion

April 4, 2014

Study Completion

January 27, 2018

Last Updated

August 9, 2019

Record last verified: 2019-08

Locations