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Non-Small Cell Lung CancerPhase 2NCT00508625

A Study of AMG 951 [rhApo2L/TRAIL] in Subjects With Previously Untreated Non-Small Cell Lung Cancer (NSCLC) Treated With Chemotherapy +/- Bevacizumab

A Phase 2 study testing AMG 951 (rhApo2L/TRAIL), Bevacizumab and Carboplatin in people with Non-Small Cell Lung Cancer, run by Amgen.

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 is a phase 2 multicenter, open label, randomized study of AMG 951 (rhApo2L/TRAIL) in subjects with previously untreated stage IIIb/IV NSCLC treated with chemotherapy with or without bevacizumab. Subjects will be assigned to a set of treatment groups depending on their eligibility to receive bevacizumab. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Small Cell Lung Cancer
What is being tested?
AMG 951 (rhApo2L/TRAIL), Bevacizumab and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
213 participants
Where
No sites listed yet
Study dates
Jun 2006to Nov 2011
Phase
Phase 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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed Non-Small Cell Lung Cancer (NSCLC). Mixed tumors will be categorized by the predominant cell type unless small cell elements are present in which case the patient is ineligible. Cytologic or histologic elements can be established on metastatic tumor aspirates or biopsy.
  • Subjects must have advanced NSCLC defined as stage IIIb with malignant pleural effusion or Stage IV or recurrent disease. Subjects with unmeasurable but evaluable disease can be included in the phase 1b study, but disease must be measurable to be included in the phase 2 study
  • Planning to receive up to 6 cycles of chemotherapy
  • ECOG performance status of 0 or 1
  • Life expectancy greater than 3 months
  • ≥18 years old
  • Subjects must sign and date a written Independent Ethics Committee (IEC)-approved Informed Consent Form
  • INR ≤ 1.2 and PTT ≤ ULN within 1 week prior to enrollment

Who cannot join

  • Disease Related
  • Prior malignancy other than NSCLC (except in situ basal cell carcinoma or in situ cervical cancer), unless have been treated with curative intent with no evidence of disease for > 3 years
  • Untreated or unstable central nervous system (CNS) metastases. Subjects with treated and stably controlled CNS metastases are eligible for cohorts A and B of the phase 2 part of the study if definitive therapy has been administered (surgery and/or radiation therapy), there is no planned treatment for brain metastases, and the subject is clinically stable and is off corticosteroids or on a stable dose of corticosteroids for at least 2 weeks prior to enrollment
  • Myocardial infarction, or unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure [New York Heart Association > class II]) within 1 year of enrollment
  • Uncontrolled hypertension defined as: systolic blood pressure > 150 mm Hg OR diastolic blood pressure > 100 mm Hg (antihypertensive therapy to achieve these parameters is allowable)
  • History of arterial thrombosis, pulmonary embolus, deep vein thrombosis or hemorrhagic disorders within 1 year of enrollment
Show all 39Show fewer
  • Recent major surgical procedure within 28 days of enrollment
  • Subjects must not have serious non-healing wound ulcer, or bone fracture within 21 days prior to enrollment
  • Persistent history of gross hemoptysis (defined as bright red blood of a ½ teaspoon or more) related to subject's NSCLC
  • Known (documented in medical notes) HIV infection
  • Active infection on day of enrollment
  • Known to be hepatitis C positive OR hepatitis B surface antigen positive
  • Subjects with Gilbert's syndrome
  • Laboratory
  • Absolute neutrophil count (ANC) < 1.5 x 10*9 /L (without granulocyte-colony stimulating factor support within 2 weeks of enrollment)
  • Platelet count < 100 x 10*9 /L (without transfusion within 2 weeks of enrollment)
  • Hemoglobin < 9 g/dL (subjects may be transfused or receive erythropoietic treatment to meet criterion)
  • Urine protein quantitative value of > 1+ on dipstick or > 30 mg/dL in urinalysis. If quantitative protein is < 500 mg in 24-hour urine collection then subject can be included
  • Significant liver dysfunction as defined by aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x upper limits of normal (ULN)
  • Alkaline phosphatase > 2.5 x ULN, or alkaline phosphatase > 5 x ULN in the presence of bone or liver metastasis
  • Total bilirubin > 1.5 x ULN
  • Calculated creatinine clearance < 50 mL/min.
  • Hypercalcemia (serum calcium > 12.0 mg/dL or symptomatic)
  • Medications
  • Prior chemotherapy (except for adjuvant chemotherapy, provided the last dose of adjuvant therapy was received at least one year prior to enrollment), hormonal therapy, radiotherapy (except palliative radiotherapy for bone metastases or radiation therapy for CNS metastases) or immunotherapy for treatment of advanced NSCLC
  • Prior drug treatment or therapy with investigational agents for NSCLC
  • Therapeutic anticoagulation treatment. Prophylactic anticoagulation of venous access devices (eg, with low-dose warfarin [1-2mg/day] or low-dose heparin) is allowed providing INR ≤ 1.2 and PTT is ≤ ULN within 1 week prior to enrollment
  • Chronic daily treatment with aspirin (> 325 mg/day) or non-steroidal anti-inflammatory agents known to inhibit platelet function. Treatment with dipyridamole, ticlopidine, clopidogrel and/or cilostazol is also not allowed.
  • General Exclusions
  • Participation in clinical trials or undergoing other investigational procedures within 30 days before study enrollment
  • Subject is evidently pregnant (e.g. positive HCG test) or is breast feeding
  • Woman or man with partner of childbearing potential not consenting to use adequate contraceptive precautions i.e. double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men.
  • Subject has known sensitivity to any of the products to be administered during the study.
  • Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with study procedures.
  • Any condition which in the investigator's opinion makes the subject unsuitable for study participation
  • Subjects enrolled and dosed in phase 1b will be excluded from phase 2
  • Exclusion criteria for phase 1b and bevacizumab treatment (cohorts C, D and E) in phase 2
  • Subjects with central nervous system tumor involvement
  • Subjects with squamous NSCLC

About this study

Official title: A Multicenter, Open Label, Randomized Study of AMG 951 in Subjects With Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated With Chemotherapy With or Without Bevacizumab

This is a phase 2 multicenter, open label, randomized study of AMG 951 (rhApo2L/TRAIL) in subjects with previously untreated stage IIIb/IV NSCLC treated with chemotherapy with or without bevacizumab.

Subjects will be assigned to a set of treatment groups depending on their eligibility to receive bevacizumab. Subjects with squamous NSCLC and/or CNS metastases will not be eligible to receive bevacizumab and will be assigned to either cohort A or B (provided all other eligibility criteria are met). Subjects who are eligible to receive bevacizumab will be assigned to cohort C, D or E. Cohorts are defined as follows:

Read more

Subjects with squamous NSCLC or CNS mets:

Cohort A: Chemotherapy alone Cohort B: Chemotherapy plus 8 mg/kg AMG 951 for 5 days

Subjects without squamous NSCLC and without CNS mets:

Cohort C: Chemotherapy and bevacizumab Cohort D: Chemotherapy, bevacizumab plus 8 mg/kg AMG 951 for 5 days Cohort E: Chemotherapy, bevacizumab plus up to 20 mg/kg AMG 951 for 2 days Approximately forty subjects will be recruited to each cohort.

Being tested
AMG 951 (rhApo2L/TRAIL), Bevacizumab, Carboplatin, Paclitaxel
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • AMG 951 (rhApo2L/TRAIL)Drug

    Also called Dulanermin

    AMG 951 is recombinant human Apo2Ligand/Tumor necrosis factor related apoptosis inducing ligand (rhApo2L/TRAIL) that triggers apoptosis through activation of death receptor 4 (DR4) and death receptor 5 (DR5).

  • BevacizumabDrug

    Also called Avastin

    Bevacizumab is a recombinant humanized version of a murine antibody to vascular endothelial growth factor (VEGF).

  • CarboplatinDrug

    Standard platinum based chemotherapy

  • PaclitaxelDrug

    Standard taxane chemotherapy

Study groups in NCT00508625
Study groupRoleWhat they receive
COther40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus Bevacizumab (15mg/kg) on day 1 of each 21 day cycle until disease progression, study drug intolerability or withdrawal of consent.
Receives: Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel
EExperimental40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus Bevacizumab (15mg/kg) on day 1 and AMG 951 (rhApo2L/TRAIL) (20mg/kg) on days 1-2 per 21 day cycle until disease progression, study drug intolerability or withdrawal of consent.
Receives: Drug: AMG 951 (rhApo2L/TRAIL); Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel
BExperimental40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus AMG 951 (rhApo2L/TRAIL) (8mg/kg) for 5 days per 21 days cycle until disease progression, study drug intolerability or withdrawal of consent.
Receives: Drug: AMG 951 (rhApo2L/TRAIL); Drug: Carboplatin; Drug: Paclitaxel
AOther40 subjects will receive up to 6 cycles of Carboplatin (AUC = 6.0mg/ml.min) and Paclitaxel (200mg/m2) only
Receives: Drug: Carboplatin; Drug: Paclitaxel
DExperimental40 subjects will receive up to 6 cycles of carboplatin (AUC=6.0mg/ml.min) and paclitaxel (200mg/m2) on day 1 of each 21 day cycle plus Bevacizumab (15mg/kg) on day 1 and AMG 951 (rhApo2L/TRAIL) (8mg/kg) on days 1-5 per 21 day cycle until disease progression, study drug intolerability or withdrawal of consent.
Receives: Drug: AMG 951 (rhApo2L/TRAIL); Drug: Bevacizumab; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

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

  1. Objective response rate (CR and PR) by modified RECIST

    Measured: Until disease progression, drug intolerability or withdrawal of consent

Secondary outcomes (6)

  1. Progression free survival

    Measured: Until disease progression, drug intolerability or withdrawal of consent

  2. Time to response

    Measured: Until disease progression, drug intolerability or withdrawal of consent

  3. Duration of response

    Measured: Until disease progression, drug intolerability or withdrawal of consent

  4. Time to progression

    Measured: Until disease progression, drug intolerability or withdrawal of consent

  5. Overall response rate (complete, partial or stable response)

    Measured: Until disease progression, drug intolerability or withdrawal of consent

  6. Overall Survival

    Measured: Until disease progression, drug intolerability or withdrawal of consent

Timeline

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

  1. First posted30 Jul 2007 (estimated)
  2. Study startJun 2006
  3. Primary completionMar 2009
  4. Study completionNov 2011

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
213 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00508625
Sponsor's protocol ID
20050190
Status last verified
Jun 2016
First submitted
26 Jul 2007
Last updated
14 Jun 2016
Results posted
No

Publications

  • Besse B, Planchard D, Veillard AS, Taillade L, Khayat D, Ducourtieux M, Pignon JP, Lumbroso J, Lafontaine C, Mathiot C, Soria JC. Phase 2 study of frontline bortezomib in patients with advanced non-small cell lung cancer. Lung Cancer. 2012 Apr;76(1):78-83. doi: 10.1016/j.lungcan.2011.09.006. Epub 2011 Dec 18.

    PubMed 22186627

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AMG 951 (rhApo2L/TRAIL), Bevacizumab and Carboplatin in people with Non-Small Cell Lung Cancer, run by Amgen.

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 8 inclusion and 39 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 14 Jun 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 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?

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?

Objective response rate (CR and PR) by modified RECIST (time frame: Until disease progression, drug intolerability or withdrawal of consent). 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 NCT00508625, 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 14 Jun 2016.

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