Brief Title
Intraperitoneal Bortezomib and Carboplatin in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer
Official Title
A Phase I Pharmacokinetic Study of Intraperitoneal CTEP-Supplied Agent Bortezomib (PS-341, NSC 681239) and Carboplatin (NSC# 241240) in Patients With Persistent or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
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.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of
intraperitoneal (IP) bortezomib (BTZ) when administered with intraperitoneal carboplatin in
women with epithelial ovarian, fallopian tube, or primary peritoneal cancer that is
persistent or recurrent and who have failed primary therapy and at least one second-line
therapy.
II. To examine the safety of administering BTZ in combination with carboplatin by the IP
route.
SECONDARY OBJECTIVES:
I. To estimate objective tumor response rate as determined by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1 criteria.
II. To determine the pharmacokinetic profile of BTZ and carboplatin when administered
intraperitoneally once every 21 days.
III. To characterize the frequency of carboplatin hypersensitivity reactions (HSR) when
administered as an intraperitoneal infusion in the context of recurrent ovarian cancer.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive bortezomib intraperitoneally (IP) and carboplatin IP on day 1. Treatment
repeats every 21 days for 6 courses in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
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)
Secondary Outcome
Objective tumor response (complete and partial response)
Condition
Fallopian Tube Clear Cell Adenocarcinoma
Intervention
Bortezomib
Study Arms / Comparison Groups
Treatment (bortezomib, carboplatin)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
33
Start Date
April 5, 2010
Completion Date
January 27, 2018
Primary Completion Date
April 4, 2014
Eligibility Criteria
Inclusion Criteria:
- 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
- Patients are required to receive, one additional cytotoxic regimen for management
of recurrent or persistent disease
- Patients are allowed to receive, but are not required to receive, two additional
cytotoxic regimens for management of recurrent or persistent disease (maximum
number of prior cytotoxic regimens including primary therapy is 4); patients are
allowed to receive, but are not required to receive, biologic (non-cytotoxic)
therapy either alone or as part of the cytotoxic regimens for management of
recurrent or persistent disease
- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl, equivalent to the
National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) version 4 grade 1
- Platelets greater than or equal to 100,000/mcl
- Creatinine less than or equal to institutional upper limit of normal (ULN)
- Bilirubin less than or equal to 1.5 x ULN (per the NCI CTCAE version 4 grade 1)
- Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) less
than or equal to 3 x ULN (per the active version of the NCI CTCAE grade 1)
- Alkaline phosphatase less than or equal to 2.5 x ULN (per the NCI CTCAE version 4
grade 1)
- Neuropathy (sensory and motor) less than or equal to the NCI CTCAE version 4 grade 1
- Prothrombin time (PT) such that international normalized ratio (INR) is =< 1.5 x ULN
(or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of
therapeutic warfarin)
- Partial thromboplastin time (PTT) =< 1.5 x ULN (heparin, low molecular weight heparin,
or alternative anticoagulants are acceptable)
- Patients who have met the pre-entry requirements
- An approved informed consent and authorization permitting release of personal health
information must be signed by the patient or guardian
- Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and be practicing an effective form of contraception
- Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy
as indicated at the lowest effective dose(s) for control of menopausal symptoms at any
time, but not progestins for management of anorexia while on protocol directed therapy
or prior to disease progression
Exclusion Criteria:
- 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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Don Dizon, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01074411
Organization ID
NCI-2011-02014
Secondary IDs
NCI-2011-02014
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Collaborators
NRG Oncology
Study Sponsor
Don Dizon, Principal Investigator, NRG Oncology
Verification Date
August 2019