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Ovarian Clear Cell CystadenocarcinomaPhase 1NCT01459380

Pegylated Liposomal Doxorubicin Hydrochloride, Carboplatin, Veliparib, and Bevacizumab in Treating Patients With Recurrent Ovarian Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

A Phase 1 study testing Bevacizumab, Carboplatin and Laboratory Biomarker Analysis in people with Ovarian Clear Cell Cystadenocarcinoma and Ovarian Endometrioid Adenocarcinoma, run by National Cancer Institute (NCI) at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This phase I trial studies the side effects and the best dose of veliparib when given together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and bevacizumab in treating patients with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has returned after previous treatment. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Bevacizumab, Carboplatin and Laboratory Biomarker Analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
13 sitesUnited States
Study dates
11 Oct 2011to 11 Feb 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must have histologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal carcinoma which is now recurrent; histologic documentation of the original primary tumor is required via the pathology report
  • Patients with the following histologic epithelial cell types are eligible: high-grade serous adenocarcinoma, endometrioid adenocarcinoma, undifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma or adenocarcinoma not otherwise specified (N.O.S.)
  • Patients must have recurrence documented by elevated cancer antigen (CA)-125 (biochemical recurrence) or clinically evident measurable or non-measurable recurrent disease
  • Biochemical recurrence is defined as a CA-125 greater than or equal to two times the upper normal limit; patients whose CA-125 is less than 100 U/mL must undergo a second confirmatory value within a period of not more than 4 weeks; patients with a level greater than or equal to 100 U/mL may be entered without confirmatory measurement; the CA-125 assessment for eligibility must be done at least 4 weeks after paracentesis or other surgical procedures
  • Detectable (non-measurable) disease is defined as symptomatic ascites or pleural effusions, solid and/or cystic abnormalities on radiographic imaging that do not meet Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 definitions for target lesions and/or biopsy proven recurrence
  • Measurable disease will be defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter 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
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  • Patients with measurable disease must have had at least one "target lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/mcl
  • This ANC cannot have been induced or supported by granulocyte colony-stimulating factors
  • Platelets greater than or equal to 100,000/mcl
  • Creatinine =< 1.5 times institutional upper limit of normal (ULN)
  • Bilirubin < 1.2 times ULN
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 3.0 times ULN
  • Alkaline phosphatase =< 2.5 times ULN
  • Left ventricular ejection fraction (LVEF) greater than or equal to institutional lower limit of normal (LLN) as determined by gated cardiac radionucleotide scan (MUGA) or echocardiogram
  • Neuropathy (sensory and motor) less than or equal to grade 1
  • Patients must have a platinum-free interval following initial platinum-based chemotherapy of at least 6 months at first recurrence; front-line therapy may have included a biologic/targeted agent (e.g., bevacizumab)
  • NOTE: Front-line treatment may have included maintenance therapy; patients receiving maintenance therapy (biological therapy, hormonal, or taxane therapy) are ELIGIBLE provided their platinum-free interval is at least 6 months from initial chemotherapy AND a minimum of 4 weeks has elapsed since their last dose of biologic/targeted or taxane therapy or a minimum of 1 week has elapsed since their last dose of hormonal therapy
  • Patients must have a Gynecologic Oncology Group (GOG) performance status of 0 or 1
  • Patients of childbearing potential must have a negative pregnancy test prior to the study entry and be practicing an effective form of contraception; if applicable, patients must discontinue breastfeeding prior to study entry
  • Patients who have met the pre-entry requirements
  • Patients must have signed an Institutional Review Board (IRB)-approved informed consent and authorization permitting release of personal health information
  • ADDITIONAL CRITERIA FOR PATIENTS BEING TREATED ON BEVACIZUMAB COHORT
  • 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) and a partial thromboplastin time (PTT) < 1.5 X ULN
  • Urine protein should be screened by urine analysis; if protein is 2+ or higher, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment
  • Patients treating with enoxaparin are eligible for inclusion in the study
  • Fertile women must agree to use adequate contraceptive measures during study therapy and for at least 6 months after the completion of bevacizumab therapy; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately

Who cannot join

  • Patients who have received more than one previous regimen of chemotherapy (maintenance is not considered a second regimen)
  • Patients who have received prior ABT-888 or any other poly-adenosine diphosphate (ADP)--ribose polymerase (PARP) inhibitor
  • Patients who have received prior PLD
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ABT-888 or other agents used in this study
  • Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and other specific malignancies are excluded if there is any evidence of other malignancy being present within the last three 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 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
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  • Patients who have received prior chemotherapy for any abdominal or pelvic tumor (other than ovarian, fallopian tube and primary peritoneal) 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 synchronous primary endometrial cancer or a history of endometrial cancer, unless all of the following conditions are met:
  • Stage not greater than IB
  • No more than superficial myometrial invasion
  • No 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 known chronic or active hepatitis or ongoing or active infection that requires parenteral antibiotics
  • 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 of childbearing potential, not practicing adequate contraception, patients who are pregnant or patients who are breastfeeding are not eligible for this trial
  • Patients with seizures or a history of seizures are ineligible
  • Patients with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, any CNS metastases, or history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage within six months of the first date of treatment on this study; patients with CNS metastases must be stable for > 3 months after treatment and off steroid treatment prior to study enrollment
  • Patients who cannot swallow pills
  • ADDITIONAL CRITERIA FOR PATIENTS BEING TREATED ON BEVACIZUMAB COHORT:
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with bevacizumab
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible
  • Urine protein should be screened by urine analysis; if protein is 2 + or higher, 24-hour urine protein should be obtained and the level should be < 1000 mg for patient enrollment
  • Serious non-healing wound, ulcer, or bone fracture
  • History of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months to day 1
  • Invasive procedures defined as follows:
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1 therapy
  • Anticipation of need for major surgical procedures during the course of the study
  • Core biopsy within 7 days prior to day 1 (D1) therapy
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to day 1
  • Known CNS disease except for treated brain metastases; treated brain metastases are defined as having no ongoing requirement for steroids and no evidence of progression or hemorrhage after treatment for at least 3 months, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]); (stable dose of anticonvulsants are allowed); treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician; patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded
  • Patients with clinically significant cardiovascular disease are excluded
  • Inadequately controlled hypertension (HTN) (systolic blood pressure [SBP] > 160 mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive medication)
  • History of cerebrovascular accident (CVA) within 6 months
  • History of myocardial infraction or unstable angina within 6 months
  • New York Heart Association grade II or greater congestive heart failure
  • Serious and inadequately controlled cardiac arrhythmia
  • Significant vascular disease (e.g. aortic aneurysm, history of aortic dissection)
  • Clinically significant peripheral vascular disease
  • Evidence of bleeding diathesis or coagulopathy
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Augusta University Medical Center

    Augusta, Georgia, 30912

  • University of Colorado Cancer Center - Anschutz Cancer Pavilion

    Aurora, Colorado, 80045

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Hillcrest Hospital Cancer Center

    Mayfield Heights, Ohio, 44124

  • Froedtert and the Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Women and Infants Hospital

    Providence, Rhode Island, 02905

Other trials in United States

About this study

Official title: A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888), and NCI Supplied Bevacizumab in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer

This phase I trial studies the side effects and the best dose of veliparib when given together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and bevacizumab in treating patients with ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that has returned after previous treatment. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as pegylated liposomal doxorubicin hydrochloride and carboplatin, may stop the growth of tumor cells by, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as bevacizumab, can block tumor growth by blocking the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumors by blocking the growth of new blood vessels necessary for tumor growth. Giving veliparib together with pegylated liposomal doxorubicin hydrochloride, carboplatin, and bevacizumab may kill more tumor cells.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the maximum-tolerated doses (MTD) and dose-limiting toxicities of two different regimens of ABT-888 (veliparib) when administered with carboplatin and PLD (Doxil, Lipodox) (pegylated liposomal doxorubicin hydrochloride) in recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer.

II. To assess the toxicity of these regimens using the Cancer Therapy Evaluation Program (CTEP) National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

III. To examine the tolerability of these treatment regimens in combination with bevacizumab at the MTD.

SECONDARY OBJECTIVES:

  1. To estimate the objective response rate (complete and partial) in patients with measurable disease.

TERTIARY OBJECTIVES:

  1. To examine the relationships between platinum-free interval, activity of ABT-888 (objective response rate) and measures of breast cancer susceptibility gene 1/2 (BRCA1/2) status including mutations, alterations, rearrangements, promoter methylation, and immunohistochemical expression).

OUTLINE: This is a dose-escalation study of veliparib. Patients are assigned to 1 of 2 treatment arms.

REGIMEN I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-7, and pegylated liposomal doxorubicin hydrochloride intravenously (IV) over 1 hour and carboplatin IV over 30 minutes on day 1.

REGIMEN II: Patients receive veliparib PO BID on days 1-28, and pegylated liposomal doxorubicin hydrochloride and carboplatin as in Regimen I.

BEVACIZUMAB: Once the MTD for veliparib has been determined, patients also receive bevacizumab IV over 30-90 minutes on days 1 and 15.

In both arms, treatment repeats every 28 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up quarterly for 1 year.

Being tested
Bevacizumab, Carboplatin, Laboratory Biomarker Analysis, Pegylated Liposomal Doxorubicin Hydrochloride, Veliparib
Medical subject headings
Fallopian Tube Neoplasms, Ovarian Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BevacizumabBiological

    Also called Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin

    Given IV

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pegylated Liposomal Doxorubicin HydrochlorideDrug

    Also called ATI-0918, Caelyx, DOX-SL, Doxil

    Given IV

  • VeliparibDrug

    Also called ABT-888, PARP-1 inhibitor ABT-888

    Given PO

Study groups in NCT01459380
Study groupRoleWhat they receive
Regimen I (intermittent veliparib)ExperimentalPatients receive veliparib PO BID on days 1-7, and pegylated liposomal doxorubicin hydrochloride IV over 1 hour and carboplatin IV over 30 minutes on day 1.
Receives: Biological: Bevacizumab; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Veliparib
Regimen II (continuous veliparib)ExperimentalPatients receive veliparib PO BID on days 1-28, and pegylated liposomal doxorubicin hydrochloride and carboplatin as in Regimen I.
Receives: Biological: Bevacizumab; Drug: Carboplatin; Other: Laboratory Biomarker Analysis; Drug: Pegylated Liposomal Doxorubicin Hydrochloride; Drug: Veliparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. DLT assessed by NCI CTCAE version 4

    Measured: 16 weeks (first 4 courses)

  2. Dose-limiting toxicity (DLT), assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

    Measured: 28 days (first course)

  3. Incidence of adverse events as assessed by CTEP version 4 of the NCI CTCAE

    Toxicity will be tabulated.

    Measured: Up to 1 year

Secondary outcomes (1)

  1. Objective tumor response (complete and partial response)

    Objective tumor response will be tabulated by regimen.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Oct 2011 (estimated)
  2. Study start11 Oct 2011
  3. Primary completion8 Jun 2016
  4. Study completion11 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01459380
Sponsor's protocol ID
NCI-2011-01977
Other IDs
NCI-2011-01977, GOG-9927, CDR0000713945, GOG-9927, GOG-9927, U10CA180868, U10CA027469
Status last verified
Jul 2019
First submitted
6 Oct 2011
Last updated
22 Jul 2019
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Bevacizumab, Carboplatin and Laboratory Biomarker Analysis in people with Ovarian Clear Cell Cystadenocarcinoma and Ovarian Endometrioid Adenocarcinoma, run by National Cancer Institute (NCI) at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 27 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DLT assessed by NCI CTCAE version 4 (time frame: 16 weeks (first 4 courses)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01459380.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2019.

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