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Epithelial Ovarian CancerPhase 2NCT01146795

Neoadjuvant Therapy for Ovarian Cancer

A Phase 2 study testing Carboplatin, Paclitaxel and Bevacizumab in people with Epithelial Ovarian Cancer and Primary Peritoneal Cancer, run by Jason D. Wright at 3 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 study is to determine the feasibility of administering neoadjuvant carboplatin, paclitaxel, and bevacizumab without excessive dose modification or cycle delay in patients with epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Carboplatin, Paclitaxel and Bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
3 sitesUnited States
Study dates
17 May 2010to 13 Apr 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 Suspected Federation of Gynecology and Obstetrics (FIGO) stage III or IV disease.
  • Cytologic or histologic diagnosis of a carcinoma felt by the investigator to be compatible with epithelial cancer of the ovary, fallopian tube, or primary peritoneum
  • Patients must have a Performance Status of 0, 1 or 2.
  • Patients with prior anthracycline exposure must have a baseline multigated acquisition scan (MUGA) or echocardiogram prior to study entry.
  • Patients must have adequate:
  • Bone marrow function: Absolute neutrophil count (ANC) greater than or equal to 1500/υl, equivalent to Common Toxicity Criteria for Adverse Events v3.0 (CTCAE) Grade 1. This ANC cannot have been induced or supported by granulocyte colony stimulating factors.
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  • Platelets greater than or equal to 100,000/υl (CTCAE Grade 0-1).
  • Hematocrit > 21%.
  • Renal function: Creatinine < 1.5 x institutional upper limit of normal (ULN), CTCAE Grade 1.
  • Hepatic function: Bilirubin less than or equal to 1.5 x ULN (CTCAE Grade 1). AST, ALT, and alkaline phosphatase less than or equal to 2.5 x ULN (CTCAE Grade 1). Aspartate transaminase (AST) and alanine transaminase (ALT)
  • Neurologic function: Neuropathy (sensory and motor) less than or equal to CTCAE Grade 1.
  • Coagulation function: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) - PT such that international normalized ratio (INR) is ≤ 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolism) and a PTT < 1.2 times the upper limit of normal.
  • Patients must have measurable disease. Patients may or may not have cancer-related symptoms.
  • Baseline CA-125 must be ≥ 70 units/mL.
  • Patients must have met all pre-entry requirements.
  • An approved informed consent and authorization permitting release of personal health information must be signed by the patient or guardian.
  • Eligible patients should be deemed as likely to be medically fit to undergo surgical cytoreduction after 3 cycles of neoadjuvant chemotherapy by a surgical gynecologic oncologist.
  • Patients may receive estrogen +/- progestin replacement.

Who cannot join

  • Patients should NOT have undergone any prior cancer directed surgery (exploration, debulking, etc), with the exception of a minor procedure such as biopsy or cytology specimen.
  • Patients who have received prior chemotherapy, immunotherapy, radiotherapy, hormonal therapy or biologic therapy for their ovarian or primary peritoneal cancer are not eligible.
  • Patients with borderline ovarian tumors, recurrent epithelial ovarian or primary peritoneal cancer or non-epithelial ovarian cancer are not eligible.
  • Patients with a CA125:CEA ratio <25. Carcinoembryonic Antigen (CEA)
  • Patients with other cancers (other than non-melanoma skin cancer) within the last five years.
  • Patients with acute hepatitis or end stage liver disease.
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  • Patients with serious non-healing wound, ulcer or bone fracture. This includes history of abdominal fistula or intra-abdominal abscess within 6 months. Patients with granulating incisions healing by secondary intention with no evidence of fascial dehiscence or infection are eligible but require weekly wound examinations.
  • History of prior gastrointestinal perforation.
  • Patients with evidence of abdominal free air not explained by paracentesis.
  • Patients with signs or symptoms of gastrointestinal obstruction including those receiving total parenteral nutrition (TPN), intravenous hydration or tube feeds.
  • Patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels by imaging, regardless of whether any chance of requiring vascular reconstruction.
  • Patients with history or evidence upon physical examination of CNS disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain 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 treated brain metastases can enter the study. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) 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 central nervous system (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. This includes:
  • Uncontrolled hypertension, defined as systolic > 140 mm Hg or diastolic > 90 mm Hg.
  • Myocardial infarction or unstable angina within 6 months of day 1 prior to registration.
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure.
  • Serious cardiac arrhythmia requiring medication. This does not include atrial fibrillation.
  • CTCAE Grade 3 or greater peripheral vascular disease.
  • History of CVA within six months.
  • Patients with known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies including hypersensitivity to any component of bevacizumab
  • Patients with clinically significant proteinuria. Urine protein should be screened by urine protein-creatinine ratio (UPCR). The UPCR has been found to correlate directly with the amount of protein excreted in a 24 hour urine collection. Specifically, a UPCR of 1.0 is equivalent to 1.0 grams of protein in a 24 hour urine collection. Obtain at least 4 ml of a random urine sample in a sterile container (does not have to be a 24 hour urine). Send sample to lab with request for urine protein and creatinine levels (separate requests). The lab will measure protein concentration (mg/dL) and creatinine concentration (mg/dL). The UPCR is derived as follows: protein concentration (mg/dL)/creatinine (mg/dL). Patients must have a UPCR < 1.0 to allow participation in the study.
  • Patients with hypertensive crises or hypertensive encephalopathy
  • History of hemoptysis (≥ ½ teaspoon of bright red blood per episode) within 1 month prior to day 1.
  • Patients with or with anticipation of a non-study related invasive procedure defined as followed:
  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to the first date of bevacizumab.
  • Major non-study related surgical procedure anticipated during the course of the study.
  • Core biopsy within 7 days prior to first date of bevacizumab.
  • Patients with a Performance Status of Grade 3 or 4 are not eligible.
  • Patients who are pregnant or nursing. Subjects of child-bearing age have to use effective means of contraception.
  • Patients under the age of 18.
  • Patients who have received prior therapy with any anti-VEGF drug, including bevacizumab. Vascular endothelial growth factor (VEGF)
  • Patients with human immunodeficiency virus (HIV).
  • Patients with medical history or conditions not otherwise previously specified which in the opinion of the investigator should exclude participation in this study. The investigator should consult the Study Chair.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Virginia

    Charlottesville, Virginia, 22908

  • Columbia University Medical Center

    New York, New York, 10032

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: Feasibility of Carboplatin, Paclitaxel and Bevacizumab Neoadjuvant Therapy for Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer

This study is to determine the feasibility of administering neoadjuvant carboplatin, paclitaxel, and bevacizumab without excessive dose modification or cycle delay in patients with epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer. This study will also investigate the rate of optimal cytoreduction, response rate and progression free and overall survival, and to assess the quality of life for patients with epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer treated with neoadjuvant carboplatin, paclitaxel and bevacizumab.

Read the detailed description

Initial treatment for ovarian cancer is usually surgical cytoreduction followed by adjuvant platinum and taxane chemotherapy. At the time of diagnosis over 75% of patients present with stage III or IV disease that has spread into the peritoneal cavity or distally. Despite a number of new chemotherapeutic regimens survival has improved only modestly over the preceding two decades. While overall 5-year survival has improved from 30% to 50%, 5-year survival remains only 25% for women with advanced stage disease. Given these findings it is clear that improved strategies for the delivery of cytotoxic and biologic agents are needed for women with advanced stage epithelial ovarian cancer.

A newer drug, called bevacizumab, has been approved by the U.S. Food and Drug Administration (FDA) for use in combination with chemotherapy in patients with colon cancer, lung cancer, and some types of breast cancer that have spread to distant sites in the body. A critical question which will need to be answered is whether or not it is feasible to administer a combination of bevacizumab with standard cytotoxic therapy using a neo-adjuvant approach for patients with epithelial cancer of the ovary, fallopian tube, or primary peritoneum.

Medical subject headings
Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms

What participants receive

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

  • CarboplatinDrug

    Also called Paraplatin

    Carboplatin will be administered at a concentration-time curve (AUC) of 5-6 (at the discretion of the physician) day 1 every 3 weeks in combination with Paclitaxel and Bevacizumab.

  • PaclitaxelDrug

    Also called Taxol

    Paclitaxel 175 mg/m2 over 3 hours day 1 every 3 weeks in combination with Carboplatin and Bevacizumab.

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab 15 mg/kg day 1 every 3 weeks in combination with Paclitaxel and Carboplatin.

Study groups in NCT01146795
Study groupRoleWhat they receive
Carboplatin, Paclitaxel, and BevacizumabExperimentalThree 21 day cycles of carboplatin, paclitaxel, and bevacizumab. After 3 cycles of chemotherapy patients will be considered for surgical cytoreduction. Patients must fulfill all criteria to be considered eligible for surgical exploration: 1) ≥50% reduction in pretreatment cancer antigen 125 (CA-125) and 2) No medical contraindications to surgery. After surgical cytoreduction all patients will receive an additional 6 cycles of chemotherapy (cycles 4-9) regardless of disease status at the time of exploration. Chemotherapy should be re-instituted within 6 weeks of the surgical procedure. Bevacizumab will be omitted from cycle 4 of chemotherapy. Patients who do NOT undergo surgical resection should receive cycles 4-9 of therapy. In this instance bevacizumab may be included in cycle 4.
Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab

What is being measured

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

  1. Number of Protocol Defined Adverse Events in Patients Receiving Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab

    This is to assess the feasibility of delivering multiple cycles of the study treatment without excessive dose modification or cycle delays. The regimen would be considered unfeasible for further study if there were 5 or more of the following events within the first 15 patients, 7 or more of these events within the first 30 patients, or 8 or more of these events within the first 45 patients:

    • Delay of day 1 of therapy > 3 weeks from the expected day 1 of that cycle
    • Febrile neutropenia requiring hospitalization
    • Grade 4 thrombocytopenia
    • Grade 1-5 gastrointestinal perforation
    • Grade 3-4 hemorrhagic toxicity
    • Grade 3-4 arterial thromboembolic complications
    • Grade 4 hypertension
    • Grade 4 proteinuria
    • Fascial dehiscence

    Measured: Up to 30 days after completion of 9 cycles of treatment and/or early discontinuation (approximately up to 12 months)

Secondary outcomes (3)

  1. Response Rate

    The percentage of patients whose cancer shrinks or disappears after treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

    Measured: Cycle 3, Cycle 6, Cycle 9 and 3 years post-treatment

  2. Quality of Life (QOL) Score

    The FACT Quality of Life (QOL) Score questionnaire is designed to assess the effects of cancer and its treatment on the quality of life, by measuring aspects of an individual's sense of well-being and ability to carry out various activities. When calculating the total QOL score, the score scale of functional well-being was reversed in order to keep consistent with other three domains. The lower the total score, the better the quality of life. The five-point scale ranges from 0 (not at all) to 4 (very much). Scoring the FACT-G is performed through a simple sum of item scores. Each subscale is scored, and a total score for the FACT-G is obtained by adding each of the subscale scores. With a total possible score greater than 100, additional scoring methods have been used to simplify interpretation. Modifications of scoring include normalizing the total score on a scale of 0-100 through mathematical transformations, as well as the use of a Trial Outcome Index (TOI).

    Measured: Baseline, Cycle 3, Cycle 6, Cycle 9

  3. Progression-free Survival (PFS)

    The length of time during and after the treatment of cancer, that a patient lives with the disease but it does not get worse.

    Measured: Up to 3 years

Timeline

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

  1. First posted22 Jun 2010 (estimated)
  2. Study start17 May 2010
  3. Primary completion13 Apr 2015
  4. Study completion13 Apr 2015

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01146795
Sponsor's protocol ID
AAAD8429
Status last verified
Jan 2021
First submitted
21 May 2010
Last updated
9 Feb 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Carboplatin, Paclitaxel and Bevacizumab in people with Epithelial Ovarian Cancer and Primary Peritoneal Cancer, run by Jason D. Wright at 3 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 18 inclusion and 33 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 9 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Number of Protocol Defined Adverse Events in Patients Receiving Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab (time frame: Up to 30 days after completion of 9 cycles of treatment and/or early discontinuation (approximately up to 12 months)). 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 NCT01146795.

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 9 Feb 2021.

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