AzTrials
AzTrials

Fallopian Tube CancerPhase 1/2NCT00436501

VEGF Trap and Docetaxel in Treating Patients With Persistent or Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cancer, or Fallopian Tube Cancer

A Phase 1/2 study testing docetaxel, ziv-aflibercept and laboratory biomarker analysis in people with Fallopian Tube Cancer and Malignant Tumor of Peritoneum, run by National Cancer Institute (NCI) at 2 sites in United States.

Completed

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

Official record
Search all trials

Trial summary

This phase I/II trial is studying the side effects and best dose of VEGF Trap when given together with docetaxel and to see how well they work in treating patients with persistent or recurrent ovarian epithelial 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?
docetaxel, ziv-aflibercept and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
58 participants
Where
2 sitesUnited States
Study dates
Jan 2007to Nov 2012
Phase
Phase 1/2
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

Criteria:

  • Histologically confirmed ovarian epithelial, primary peritoneal, or fallopian tube cancer:

Persistent or recurrent disease

  • Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques:
  • Must have >= 1 target lesion to assess response;
  • Tumors within a previously irradiated field are considered nontarget lesions
  • Must have received 1 prior platinum-based chemotherapy regimen (for primary disease) containing carboplatin, cisplatin, or other organoplatinum compound:

Initial treatment may have included any of the following:

  • High-dose therapy;
  • Consolidation therapy;
  • Extended therapy administered after surgical or nonsurgical assessment
  • AND Must have received 1 prior platinum-based chemotherapy regimen (for primary disease) containing carboplatin, cisplatin, or other organoplatinum compound:

One additional cytotoxic regimen for recurrent or persistent disease allowed

  • No history or evidence of CNS disease, including primary brain tumor or brain metastases
  • Zubrod performance status 0-2 (0-1 for patients who received 2 prior regimens [taxane and/or platinum regimens are counted separately])
  • Absolute neutrophil count >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9 g/dL
  • Bilirubin normal
  • aspartate aminotransferase / alanine aminotransferase (AST/ALT) < 2.5 times upper limit of normal (ULN)
  • Creatinine < 1.5 times ULN OR creatinine clearance > 60 mL/min
  • Prothrombin Time (PT)/international normalized ratio (INR) < 1.5 OR in-range INR 2-3 (if patient is on a stable dose of therapeutic warfarin or low molecular weight heparin)
  • PTT < 1.2 times control
  • Urine protein:creatinine ratio < 1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for at least 6 months after completion of study treatment
  • No active infection requiring antibiotics
  • No sensory and motor neuropathy >= grade 2
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to VEGF Trap, Magnevist, or fludeoxyglucose F 18
  • No history of allergic reaction to paclitaxel or docetaxel or to products mixed in Cremophor EL or Tween 80
  • No active bleeding or pathologic condition that would carry a high risk of bleeding, including any of the following:

Known bleeding disorder; Coagulopathy; Peptic ulcer disease; Diverticulitis; Tumor involving major vessels

  • No active and/or untreated pulmonary embolism, deep vein thrombosis, or other thromboembolic event (i.e., any condition associated with aberrant clotting or migration of an induced clot)
  • No history or evidence of other CNS disease, including any of the following:

Seizures not controlled with standard medical therapy; Cerebrovascular accident; Transient ischemic attack; Subarachnoid hemorrhage within the past 6 months

  • No clinically significant cardiovascular disease, including any of the following:

Uncontrolled hypertension (i.e., systolic blood pressure [BP] > 150 mm Hg or diastolic BP > 100 mm Hg; systolic BP > 180 mm Hg and diastolic BP < 90 mm Hg OR diastolic BP > 90 mm Hg on >= 2 measurements within the past 3 months); Myocardial infarction; Coronary or peripheral artery bypass graft

  • No clinically significant cardiovascular disease, including any of the following:

New York Heart association class III or IV congestive heart failure; Serious cardiac arrhythmia requiring medication; Peripheral vascular disease >= grade 2; Unstable angina within the past 6 months; Clinically significant peripheral artery disease (e.g., claudication) within the past 6 months

  • No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies
  • Able to undergo an MRI scan:

No claustrophobia; No implanted devices or metallic foreign bodies not compatible with MRI (e.g., ferromagnetic implants or pacemakers); No known history of allergic reaction to gadolinium contrast agents

  • No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
  • No significant traumatic injury within the past 28 days
  • Recovered from prior therapy to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 grade =< 1:

Alopecia allowed

  • No prior VEGF Trap
  • No prior cancer treatment that would preclude study treatment
  • Prior paclitaxel allowed
  • Prior docetaxel for primary or recurrent disease allowed provided the following criteria are met:

No disease progression during therapy; No disease relapse within 3 months of completing therapy; No persistent disease at the completion of primary therapy

  • More than 7 days since prior placement of a vascular access device or core biopsy
  • At least 1 week since prior hormonal therapy for the malignant tumor
  • At least 4 weeks since other prior therapy, including immunologic agents (6 weeks for nitrosoureas or mitomycin C)
  • More than 28 days since prior major surgery, open biopsy, dental extraction, or other dental surgery/procedure resulting in an open wound
  • No concurrent major surgery
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer therapy
  • No other concurrent investigational agents
  • No concurrent hematopoietic growth factors during course 1 of phase I
  • Concurrent hormone replacement therapy allowed
  • White blood count (WBC) >= 3,000/mm^3

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Virginia Health System

    Charlottesville, Virginia, 22903

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I/II and Pharmacokinetic Study of Docetaxel Plus VEGF Trap (AVE0005, NSC# 724770) in Patients With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancer

This phase I/II trial is studying the side effects and best dose of VEGF Trap when given together with docetaxel and to see how well they work in treating patients with persistent or recurrent ovarian epithelial cancer, primary peritoneal cancer, or fallopian tube cancer. VEGF Trap may stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving VEGF Trap together with docetaxel may kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. Determine the safety and tolerability of VEGF Trap and docetaxel in patients with persistent or recurrent ovarian epithelial, primary peritoneal, or fallopian tube cancer. (Phase I [closed to accrual as of 3/14/2008]) II. Determine the maximum tolerated dose of VEGF Trap in these patients. (Phase I [closed to accrual as of 3/14/2008]) III. Determine the pharmacokinetics of VEGF Trap when administered alone and in combination with docetaxel in these patients. (Phase I [closed to accrual as of 3/14/2008]) IV. Determine the effects of VEGF Trap on tumor perfusion and metabolism in these patients. (Phase I [closed to accrual as of 3/14/2008]) V. Determine the effect of VEGF Trap and docetaxel on circulating endothelial precursors and circulating endothelial cells in these patients. (Phase I [closed to accrual as of 3/14/2008]) VI. Determine the frequency of clinical response (partial response and complete response) in patients treated with this regimen. (Phase II [open to accrual as of 5/9/2008]) VII. Determine the progression-free survival (PFS) and overall survival (OS) of patients treated with this regimen. (Phase II [open to accrual as of 5/9/2008])

SECONDARY OBJECTIVES:

  1. Determine the duration of PFS and OS of patients treated with this regimen. (Phase II) II. Determine the frequency and severity of adverse effects of this regimen in these patients. (Phase II) III. Determine the proportion of patients with PFS at 6 months. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of VEGF Trap followed by a phase II study.

PHASE I (closed to accrual as of 3/14/2008): Patients receive VEGF Trap IV over 1 hour on day 1 of course 1. Patients then receive VEGF Trap IV over 1 hour and docetaxel IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 or 6 patients experience dose-limiting toxicity.

PHASE II (opened to accrual as of 5/9/2008): Patients receive VEGF Trap at the MTD determined in phase I and docetaxel as in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients enrolled in phase I (closed to accrual as of 3/14/2008) undergo blood sample collection periodically for pharmacokinetic studies and surrogate marker studies. These patients also undergo dynamic contrast-enhanced MRI, fludeoxyglucose F 18 positron emission tomography, and CT scan at baseline and on day 1 of courses 1 and 2 to evaluate blood flow parameters and metabolic activity of tumors. Patients enrolled in phase I (closed to accrual as of 3/14/2008) and phase II will also undergo blood collection for Anti-VEGF trap antibody.

After the completion of study treatment, patients are followed at 1 and 2 months and then periodically thereafter.

Being tested
docetaxel, ziv-aflibercept, laboratory biomarker analysis, pharmacological study
Keywords
primary peritoneal cavity cancer, Ovarian Epithelial Cancer, Peritoneal Cancer, Fallopian Tube Cancer, VEGF Trap, aflibercept, vascular endothelial growth factor trap, Zaltrap, docetaxel, RP 56976, Taxotere, TXT
Medical subject headings
Fallopian Tube Neoplasms, Carcinoma, Ovarian Epithelial

What participants receive

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

  • docetaxelDrug

    Also called RP 56976, Taxotere, TXT

    25 mg/m^2 given intravenously (IV) over 1 hour (+/- 10 minutes) following VEGF Trap every 3 weeks starting cycle 1 (21 day cycles)

  • ziv-afliberceptBiological

    Also called aflibercept, vascular endothelial growth factor trap, VEGF Trap, Zaltrap

    Starting dose 2 mg/kg given IV Cycle 0. Phase I Group: Every 3 weeks beginning with Cycle 0 (Completed 03/14/2008); Phase II Group: Every 3 weeks starting cycle 1 (Opened 05/09/2008).

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT00436501
Study groupRoleWhat they receive
Treatment (VEGF Trap, Docetaxel)ExperimentalPhase I (closed to accrual as of 3/14/2008): Patients receive VEGF Trap IV over 1 hour on day 1 of course 1. Patients then receive VEGF Trap IV over 1 hour and docetaxel IV over 1 hour on day 1 in all subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of VEGF Trap until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 or 6 patients experience dose-limiting toxicity.
Receives: Drug: docetaxel; Biological: ziv-aflibercept; Other: laboratory biomarker analysis; Other: pharmacological study
Phase II Treatment (VEGF Trap, Docetaxel)ExperimentalPhase II (opened to accrual as of 5/9/2008): Patients receive VEGF Trap at the MTD determined in phase I and docetaxel as in phase I. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: docetaxel; Biological: ziv-aflibercept

What is being measured

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

  1. Maximum Tolerated Dose of VEGF Trap (Phase I)

    Escalating dose levels of VEGF Trap were administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose (MTD). The MTD is defined as the highest dose level below which 2 or more patients encounter a dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD established on absence of observed DLT(s) in either cycle 0 (single agent) or cycle 1 (combination therapy) of any given dose level.

    Measured: 21 day cycle, up to 3 cycles

  2. Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST)

    Frequency of clinical response (partial response or complete response) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance all target lesions; Partial Response (PR): >/= 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): >/= 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1+ new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.

    Measured: Up to 6 months

  3. Median Overall Survival (OS) (Phase II)

    Overall survival was defined from the date of study entry until death or date of last contact. Median survival time points calculated in the method of Kaplan-Meier. Standard RECIST criteria followed to evaluate response and progression, and all documented responses required confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, response assessment consistently done after two additional cycles of therapy.

    Measured: Time from start of treatment to time of progression, assessed up to 6 years.

  4. Overall Objective Response Rate According to RECIST (Phase II)

    The percentage of participants in the Phase II arm with an objective response defined as a measurable response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Standard RECIST criteria were followed to evaluate response and progression. All documented responses were required to undergo confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, this response assessment was consistently done after two additional cycles of therapy.

    Measured: Up to 6 months

  5. Median Progression-Free Survival (PFS) (Phase II)

    Progression-Free Survival was calculated from study entry until documented disease, death or date of last contact.

    Measured: Time from start of treatment to time of progression, assessed up to 6 years.

Secondary outcomes (3)

  1. Overall Median Duration of Response (Phase II)

    Duration of the response from time response is achieved until disease progression is detected. Response assessed following treatment (every 3 weeks) for disease progression. Study duration January 2007 to May 2013, approximately six and half years.

    Measured: Response assessed following treatment (every 3 weeks), up to 6 years. Study duration January 2007 to May 2013.

  2. Number of Participants With Treatment-related Adverse Effects as Assessed by NCI CTCAE v3.0 (Phase II)

    Number of participants with adverse effects of treatment. Frequency and severity of adverse effects of treatment as assessed by NCI CTCAE v3.0 (Phase II)

    Measured: Up to 6 years

  3. Number of Participants With PFS (Phase II)

    Progression-free survival (PFS) defined as number of participants out of total in arm that had no disease progression as measured at 6 months. Standard RECIST criteria used to evaluate response and progression. All documented responses required confirmation by imaging, examination, or both, no sooner than 4 weeks after initial documentation of response. In the absence of new symptoms, response assessment was consistently done after two additional cycles of therapy.

    Measured: 6 months

Timeline

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

  1. First posted19 Feb 2007 (estimated)
  2. Study startJan 2007
  3. Primary completionMar 2011
  4. Study completionNov 2012

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
58 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00436501
Sponsor's protocol ID
NCI-2009-00218
Other IDs
2006-0329, P50CA083639
Status last verified
Feb 2019
First submitted
15 Feb 2007
Last updated
26 Feb 2019
Data monitoring committee
No

Publications

  • Coleman RL, Duska LR, Ramirez PT, Heymach JV, Kamat AA, Modesitt SC, Schmeler KM, Iyer RB, Garcia ME, Miller DL, Jackson EF, Ng CS, Kundra V, Jaffe R, Sood AK. Phase 1-2 study of docetaxel plus aflibercept in patients with recurrent ovarian, primary peritoneal, or fallopian tube cancer. Lancet Oncol. 2011 Nov;12(12):1109-17. doi: 10.1016/S1470-2045(11)70244-3. Epub 2011 Oct 10.

    PubMed 21992853

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing docetaxel, ziv-aflibercept and laboratory biomarker analysis in people with Fallopian Tube Cancer and Malignant Tumor of Peritoneum, run by National Cancer Institute (NCI) at 2 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?

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 26 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 combined 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.

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 11 Mar 2015). 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?

Maximum Tolerated Dose of VEGF Trap (Phase I) (time frame: 21 day cycle, up to 3 cycles). The study lists 5 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 NCT00436501, which also lists 1 linked publication.

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 26 Feb 2019; AzTrials last refreshed its copy on 6 Nov 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in