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Breast CancerPhase 1NCT01423123

Combination of Weekly Paclitaxel With Neratinib and Trastuzumab in Women With Metastatic HER2-positive Breast Cancer

A Phase 1 study testing Paclitaxel, trastuzumab and Neratinib in people with Breast Cancer, run by NSABP Foundation Inc at 4 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

The FB-8 study is designed as an open label, single arm, Phase I dose-escalation study evaluating the combination of weekly paclitaxel with neratinib and trastuzumab in women with metastatic, HER2-positive breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Breast Cancer
What is being tested?
Paclitaxel, trastuzumab and Neratinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
4 sitesUnited States
Study dates
May 2011to Mar 2014
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

  • Co-morbid conditions should be taken into consideration, but not the diagnosis of metastatic breast cancer.
  • Patients of reproductive potential must agree to use an effective non-hormonal method of contraception during therapy and for at least 6 months after the last dose of study therapy.
  • The ECOG performance status must be 0, 1, or 2.
  • Patients must have the ability to swallow oral medication.
  • Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast.
  • There must be documentation that the patient has evidence (measurable or non-measurable) of metastatic breast cancer. Histologic confirmation of metastatic disease is not required.
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  • Patients must have ER analysis performed on the primary tumor prior to study entry. If ER analysis is negative, then PgR analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
  • Breast cancer must be determined to be HER2-positive prior to study entry. Assays using FISH or CISH require gene amplification. Assays using IHC require a strongly positive (3+) staining score.
  • At the time of study entry, blood counts performed within 4 weeks prior to study entry must meet the following criteria: ANC must be greater than or equal to 1000/mm3; Platelet count must be greater than or equal to 100,000/mm3; Hemoglobin must be greater than or equal to 9 g/dL
  • The following criteria for evidence of adequate hepatic function performed within 4 weeks prior to study entry must be met: total bilirubin must be less than or equal to 1.5 x ULN; AST and ALT must be less than or equal to 2.5 x ULN for the lab or less than or equal to 5 x ULN if liver metastasis
  • Serum creatinine performed within 4 weeks prior to study entry must be less than or equal to 1.5 x ULN for the lab.
  • The LVEF assessment by 2-D echocardiogram or MUGA scan performed within 90 days prior to study entry must be greater than or equal to 50% regardless of the facility's LLN.

Who cannot join

  • Previous therapy with neratinib for any malignancy.
  • Symptomatic brain metastases or brain metastases requiring chronic steroids to control symptoms.
  • Active hepatitis B or hepatitis C with abnormal liver function tests.
  • Intrinsic lung disease resulting in dyspnea.
  • Active infection or chronic infection requiring chronic suppressive antibiotics.
  • Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
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  • Persistent greater than or equal to grade 2 diarrhea regardless of etiology.
  • Sensory or motor neuropathy greater than or equal to grade 2, as defined by the NCI CTCAE v3.0.
  • Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication.
  • Chronic daily treatment with corticosteroids with a dose of greater than or equal to 10 mg/day methylprednisolone equivalent (excluding inhaled steroids).
  • Uncontrolled hypertension defined as a systolic BP greater than 150 mmHg or diastolic BP greater than 90 mmHg, with or without anti-hypertensive medications (Patients with hypertension that is well controlled on medication are eligible.)
  • Cardiac disease (history of and/or active disease) that would preclude the use of any of the drugs included in the treatment regimen. This includes but is not confined to: Active cardiac disease: symptomatic angina pectoris within the past 90 days that required the initiation of or increase in anti-anginal medication or other intervention; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromise in cardiac function; and symptomatic pericarditis. History of cardiac disease: myocardial infarction documented by elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LV function; history of documented CHF; and documented cardiomyopathy
  • Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow up.
  • Pregnancy or lactation at the time of study entry. (Note: Pregnancy testing should be performed within 14 days prior to study entry according to institutional standards for women of childbearing potential.)
  • The investigator should assess the patient to determine if she has any psychiatric or addictive disorder or other condition that, in the opinion of the investigator, would preclude her from meeting the study requirements.
  • Use of any investigational agent within 4 weeks prior to study entry.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • West Virginia University Hospitals

    Morgantown, West Virginia, 26506-9162

  • Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08901

  • NSABP Foundation, Inc.

    Pittsburgh, Pennsylvania, 15212

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15232-1305

Other trials in United States

About this study

Official title: A Phase I Dose-Escalation Study Evaluating the Combination of Weekly Paclitaxel With Neratinib and Trastuzumab in Women With Metastatic HER2-positive Breast Cancer

The FB-8 study is designed as an open label, single arm, Phase I dose-escalation study evaluating the combination of weekly paclitaxel with neratinib and trastuzumab in women with metastatic, HER2-positive breast cancer. The primary aim of this study is to determine the safety and tolerability of the three-drug combination.

Read the detailed description

Patients will receive concurrent therapy with paclitaxel (80 mg/m2 IV on days 1, 8, and 15 of a 28-day cycle), trastuzumab (4 mg/kg IV loading dose, then 2 mg/kg IV weekly), and neratinib. The neratinib dose-escalation will include 4 dose levels (120 mg, 160 mg, 200 mg, and 240 mg) as a daily oral dose.

The neratinib dose-escalation for the study will proceed on the basis of dose-limiting toxicity (DLT) during cycle 1. DLT will be defined as the occurrence of 1 or more of the following events during cycle 1: any grade diarrhea that is associated with fever or dehydration; grade 3 diarrhea lasting more than 2 days on optimal medical therapy; grade 4 diarrhea of any duration; grade 3 or 4 neutropenia associated with fever; grade 4 neutropenia lasting more than 7 days; grade 4 thrombocytopenia; grade 3 or 4 non-hematological toxicity; or any toxicity-related delay of more than 2 weeks to initiate cycle 2. Patients will be enrolled at the next dose level when all evaluable patients at the same dose level have completed the first treatment cycle. Enrolled patients will remain on the assigned dose level treatment until toxicity or disease progression.

Conditions
Breast Cancer
Being tested
Paclitaxel, trastuzumab, Neratinib
Keywords
Paclitaxel, Trastuzumab, Neratinib, Breast Cancer, HER2-positive
Medical subject headings
Breast Neoplasms

What participants receive

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

  • PaclitaxelDrug

    80 mg/m2 IV on days 1, 8, and 15 every 28 days until disease progression.

  • trastuzumabBiological

    4 mg/kg IV loading dose, then 2 mg/kg IV weekly until disease progression.

  • NeratinibDrug

    Dose level 1: 120 mg/day orally; Dose level 2: 160 mg/day orally; Dose level 3: 240 mg/day orally; Dose level 4: 200 mg/day orally.

Study groups in NCT01423123
Study groupRoleWhat they receive
NeratinibExperimentalPaclitaxel (80 mg/m2 IV on days 1, 8, and 15 every 28 days) and trastuzumab (4 mg/kg/ loading dose, then 2 mg/kg) IV weekly beginning on day 1 of paclitaxel, neratinib orally daily beginning on day 1 of paclitaxel until disease progression.
Receives: Drug: Paclitaxel; Biological: trastuzumab; Drug: Neratinib

What is being measured

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

  1. Safety and tolerability of the three-drug combination

    Number of patients experiencing dose limiting toxicities (DLT).

    Measured: Through 6 months after last dose

Secondary outcomes (2)

  1. Overall response rate

    Number of patients with disappearance of all target lesions; Number of patients with at least a 30% decrease in the sum of the longest diameter (LD) of target lesions; patients with neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as a reference the smallest sum LD since baseline.

    Measured: Measured at 24 weeks from start of therapy.

  2. Progression-free interval

    Number of patients with at least a 20% increase in the sum of the LD of target lesions, taking as a reference the smallest sum LD recorded since baseline or the appearance of one or more new lesions.

    Measured: Time to disease progression up to 15 months.

Timeline

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

  1. First posted25 Aug 2011 (estimated)
  2. Study startMay 2011
  3. Primary completionAug 2012
  4. Study completionMar 2014

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
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01423123
Sponsor's protocol ID
NSABP FB-8
Other IDs
WS1554503
Status last verified
Jul 2014
First submitted
19 Aug 2011
Last updated
8 Jul 2014
Results posted
No
Data monitoring committee
No

Publications

  • Jankowitz RC, Abraham J, Tan AR, Limentani SA, Tierno MB, Adamson LM, Buyse M, Wolmark N, Jacobs SA. Safety and efficacy of neratinib in combination with weekly paclitaxel and trastuzumab in women with metastatic HER2-positive breast cancer: an NSABP Foundation Research Program phase I study. Cancer Chemother Pharmacol. 2013 Dec;72(6):1205-12. doi: 10.1007/s00280-013-2262-2.

    PubMed 24077916

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Paclitaxel, trastuzumab and Neratinib in people with Breast Cancer, run by NSABP Foundation Inc at 4 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 12 inclusion and 16 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 8 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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?

Safety and tolerability of the three-drug combination (time frame: Through 6 months after last dose). 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 NCT01423123, 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 8 Jul 2014.

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