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Breast CancerPhase 1/2NCT01479179

Trastuzumab in Combination With AMG 479 in HER-2 Overexpressing MBC Progressing on Trastuzumab

A Phase 1/2 study testing AMG 479 and Trastuzumab in people with Breast Cancer, run by M.D. Anderson Cancer Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The goal of Phase 1 of this clinical research study is to test the safety and tolerability of AMG 479 when given with trastuzumab. The goal of Phase 2 of this clinical research study is to learn if the combination of AMG 479 and trastuzumab can help to control 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?
AMG 479 and Trastuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Nov 2012to Nov 2015
Phase
Phase 1/2
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

  • History of biopsy-proven HER-2-overexpressing breast cancer and radiographic evidence of metastatic disease. The HER-2 status can be determined either by immunohistochemistry (score, 3+) or by fluorescence in situ hybridization.
  • Patients must have received anthracycline-, taxane- and capecitabine-based chemotherapy for breast cancer. In addition, patients must have developed progressive disease to trastuzumab- or lapatinib-based therapy within the last 3 months. Patients who develop metastatic breast cancer within 3 months after receiving trastuzumab or lapatinib in the adjuvant and/or neoadjuvant setting are eligible. Three prior lines of HER2-directed therapy (containing either trastuzumab or lapatinib) for metastatic breast cancer are allowed.
  • Woman >/=18 years old.
  • Performance status 0-2 (by Eastern Cooperative Oncology Group {ECOG} scale).
  • Laboratory parameters: Absolute neutrophil count (ANC) 1.0 x 10^9/L or higher; Platelet count 100,000 x 10^9/L or higher; Hemoglobin 9.0 g/dL or higher; Partial thromboplastin (PTT) </= 1.3 x upper limit of normal (ULN) and international normalized ratio (INR) </= 1.5, unless subject is on anticoagulation therapy. Subjects on therapeutic anticoagulation are eligible if there is no bleeding and they are on a stable dose of anticoagulation therapy (eg, on coumadin with an INR of 2 to 3) for at least 7 days before registration(prior to the start of therapy). Continued in inclusion #6.
  • Continuation from # 5: Serum creatinine </= 1.5 x the ULN or calculated creatinine clearance (by Cockcroft-Gault formula) >/=40 mL/min; Aspartate aminotransferase (AST) </= 2.5 x ULN; Alanine aminotransferase (ALT) </= 2.5 x ULN; Alkaline phosphatase </= 2.5 x ULN (</= 5 x ULN with bone/liver metastases ); Bilirubin </= 1.5 x ULN.
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  • Glycosylated hemoglobin (HgbA1c)</= 8%
  • Fasting blood glucose </= 160 mg/dL (Fasting will require subjects to refrain from all food and beverage [except water] for at least 8 hours). Documentation will confirm patient compliance with nothing by mouth (NPO) status prior to lab exam.
  • Patients must not be pregnant. A pregnancy test will be obtained if the patient is a woman of child-bearing potential, defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses at any time in the preceding 24 consecutive months).
  • Patients must have signed an informed consent document stating that they understand the investigational nature of the proposed treatment.
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/= 20 mm with conventional techniques, including palpation, plain x-ray, or magnetic resonance imaging (MRI), or or >/= 10 mm with spiral computed tomography (CT) scan. Bone metastases and pleural effusions are not considered measurable disease.
  • Patients may not be receiving any other investigational agents within 30 days of registration.
  • Left ventricular ejection fraction determined by echocardiogram or multiple-gated acquisition scan (MUGA) (cardiac scan) must be 50% or higher.

Who cannot join

  • Central nervous system (CNS) metastases , unless previously treated by either radiation therapy and/or surgical resection, clinically stable and off corticosteroids. Subjects with a history of CNS metastases that are both treated and stably controlled are eligible if all of the following apply: therapy has been administered (surgery and/or radiation therapy); there is no additional treatment planned for brain metastases; the subject is clinically stable; the subject is off corticosteroids or on a stable dose of corticosteroids for at least 14 days prior to enrollment
  • Prior malignancy (other than in situ cervical cancer, or basal cell or squamous cell carcinoma of the skin), unless treated with curative intent and without evidence of disease for 3 years or longer.
  • Administration of other prior anticancer therapies within 4 weeks of enrollment, except Trastuzumab and Lapatinib.
  • Toxicities related to prior anticancer treatment (except alopecia) that have not resolved to </= grade 1 according to common terminology criteria for adverse events (CTCAE V4.0) before registration or prior to start of therapy.
  • Prior treatment with investigational treatment targeted to IGF axis including, but not limited to, CP-751,871, IM-A12, RO4858696.
  • Previous exposure to AMG 479.
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  • Currently receiving systemic antibiotic therapy for the treatment of an active infection.
  • History of bleeding diathesis.
  • Known positive test for human immunodeficiency virus, or chronic hepatitis B or C infection.
  • Any co-morbid medical condition that may put the subject at significant risk for toxicity.
  • Major surgical procedure within 28 days of registration (prior to the start of therapy).
  • Minor surgical procedures within 7 days of registration although placement of central access device, fine needle aspiration, thoracentesis or paracentesis > 1 day before registration is acceptable.
  • Known inability to tolerate intravenous (IV) drug administration.
  • Has not yet completed at least 30 days before registration since ending other investigational device or drug study(s)
  • Subject has known sensitivity to any of the products to be administered during dosing.
  • Subject will not be available for follow-up assessments.
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of venous thromboembolism.
  • Patient with reproductive potential who will not agree to use one highly effective method of contraceptive such as implants, injectables, intrauterine devices (IUDs) such as copper T or Levonorgestrel-releasing intrauterine system (LNG-IUS), sexual abstinence, vasectomised partner, or condom or occlusive cap (diaphragm or cervical/vault cap) supplemented with the use of a spermicide during treatment.
  • Poorly controlled diabetes mellitus
  • Patient with hearing impairment of > grade 3.

About this study

Official title: Phase I/II Study of Trastuzumab in Combination With AMG 479, A Fully Human Monoclonal Antibody Against Insulin-Like Growth Factor Type 1 Receptor (IGF-1R), in Patients With HER-2 Overexpressing Metastatic Breast Cancer Progressing on Trastuzumab-Based or Lapatinib-based Therapy

The goal of Phase 1 of this clinical research study is to test the safety and tolerability of AMG 479 when given with trastuzumab.

The goal of Phase 2 of this clinical research study is to learn if the combination of AMG 479 and trastuzumab can help to control breast cancer.

AMG 479 is designed to block tumor cells from growing and spreading.

Trastuzumab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell.

Read the detailed description

Phase 1 and Phase 2 of the Study:

If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Groups of 3 participants will be enrolled in the Phase 1 portion of the study. There are 2 dose levels that will be tested in Phase 1.

If you are enrolled in the Phase 1 portion, the dose of AMG 479 you receive will depend on when you joined this study. The first group of participants will receive the higher dose level of AMG 479. If there are intolerable side effects, the next group will receive the lower dose.

If you are enrolled in the Phase 2 portion, you will receive AMG 479 at the highest dose that was tolerated in the Phase 1 portion.

All participants will receive the same dose level of trastuzumab.

Study Drug Administration:

You will receive AMG 479 by vein over 60-120 minutes on Day 1 of each 21-day cycle.

You will receive trastuzumab by vein over 30-90 minutes on Day 1 of each cycle.

If you are already receiving trastuzumab at the time you join the study, you will continue to receive the standard dose of trastuzumab. If the last dose of trastuzumab was given more than 1-3 weeks before you joined the study (depending on the dose previously received), then you will receive a higher "loading" dose of trastuzumab followed by the standard dose.

Study Visits:

At every visit, you will be asked about any side effects you may have had.

Your vital signs will be checked before, during, and after each infusion of AMG 479.

On Day 1 of Cycle 1, blood (about 5 tablespoons) will be drawn for routine tests.

If you are in Phase 1, blood (about 1 tablespoon each time) will be drawn for pharmacokinetic (PK) testing 2 times (before and after the study drug dose) on Day 1 of Cycles 1 and 2. PK testing measures the amount of study drug in the body at different time points.

On Day 8 of Cycle 1, blood (about 1 tablespoon) will be drawn for routine tests.

On Day 15 of Cycle 1:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Blood (about 1 tablespoon) will be drawn for routine tests.
  • Your performance status and any updates to your medical history will be recorded.

On Day 1 of Cycles 2, 4, and 6, you will have CT or MRI scans to check the status of the disease.

On Day 1 of Cycles 2 and beyond:

  • Blood (about 1-2 teaspoons) will be drawn for blood sugar tests. You will need to fast for 8 hours before these tests.
  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status and any updates to your medical history will be recorded.
  • Blood (about 1 tablespoon) will be drawn for routine tests.

You will have a PET-CT scan at Week 3 if you had a PET-CT scan at screening.

On Day 8 of Cycles 1-3, blood (about 1½ teaspoons) will be drawn to check your blood clotting function.

Every 3 months, you will have either an ECHO or MUGA scan to check your heart function.

In certain cases with your doctor's permission, the study visits may occur 1 day earlier or later than described above. If you are having side effects, extra clinic visits may be needed.

Length of Treatment:

You may continue taking the study drugs for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drugs if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment visit.

End of Treatment Visit:

Within 30 days after the last study drug dose:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • You will be asked if you have had any side effects and about any drugs you may be taking.
  • Any updates to your medical history will be recorded.
  • Blood (about 3 tablespoons) will be drawn for routine tests.
  • You will have a hearing test
  • If you have not had one in the last 30 days or after your last treatment, you will have an ECHO or MUGA scan to check your heart function.
  • If the doctor thinks it is needed, you will have CT or MRI scans to check the status of the disease.
  • If you are in Phase 1, blood (about 1 tablespoon) will be drawn for PK testing.

This is an investigational study. Trastuzumab is FDA approved and commercially available for the treatment of breast cancer. AMG-479 is not FDA approved or commercially available. AMG-479 is currently being used for research purposes only.

Up to 35 patients will take part in this study. All will be enrolled at MD Anderson.

Conditions
Breast Cancer
Being tested
AMG 479, Trastuzumab
Keywords
Breast Cancer, Metastatic Breast Cancer, HER-2-overexpressing breast cancer, Human epidermal growth factor receptor, AMG 479, Trastuzumab, Herceptin
Medical subject headings
Breast Neoplasms

What participants receive

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

  • AMG 479Drug

    Phase I Starting Dose: 18 mg/kg by vein on Day 1 of a 21 day cycle.

    Phase II Starting Dose: Maximum tolerated dose from Phase I.

  • TrastuzumabDrug

    Also called Herceptin

    Phase I and II Starting Dose: 8 mg/kg by vein on Day 1 of a 21 day cycle.

    Phase I and II Maintenance Dose: 6 mg/kg by vein on Day 1 of a 21 day cycle.

Study groups in NCT01479179
Study groupRoleWhat they receive
AMG 479 + TrastuzumabExperimentalAMG 479 18 mg/kg or 12 mg/kg intravenously (IV) 30 minutes after trastuzumab. Trastuzumab loading dose (Week 1) 8 mg/kg IV over 90 minutes; maintenance dose 6 mg/kg IV over 30 minutes every 3 weeks.
Receives: Drug: AMG 479; Drug: Trastuzumab

What is being measured

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

  1. Maximum tolerated dose (MTD)

    Maximum tolerated dose (MTD) is highest dose for which one or fewer dose limiting toxicities (DLTs) are experienced in 6 participants. DLT is defined as a grade 3, or higher hematological or non-hematological toxicity related to study (AMG-479) drug or combination of AMG 479 and trastuzumab therapy during first cycle (21 days).

    Measured: After first 21 day cycle

Secondary outcomes (1)

  1. Clinical Benefit Rate (CBR)

    Efficacy measured by clinical benefit rate {CR (Complete response) + PR (Partial response) + SD (stable disease) >/= 24 weeks}. Response assessment by CT or MRI. CR: Disappearance of all target lesions; PR: >30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; PD: =/>20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1 or > new lesions. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started.

    Measured: Baseline to 24 weeks

Timeline

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

  1. First posted24 Nov 2011 (estimated)
  2. Study startNov 2012
  3. Primary completionNov 2015 (estimated)

Why it stopped: Drug sponsor decision to discontinue study.

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01479179
Sponsor's protocol ID
2009-0542
Status last verified
Oct 2016
First submitted
21 Nov 2011
Last updated
26 Oct 2016
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AMG 479 and Trastuzumab in people with Breast Cancer, run by M.D. Anderson Cancer Center.

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 13 inclusion and 22 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: withdrawn, as of the sponsor's last update on 26 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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 (MTD) (time frame: After first 21 day cycle). 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 NCT01479179.

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 Oct 2016.

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