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Carcinoma, Non-Small-Cell LungPhase 3NCT02629848

Study of Motesanib (AMG 706) in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer

A Phase 3 study testing Motesanib, Paclitaxel and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Takeda.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This study will evaluate progression free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, and safety of motesanib (AMG706) in combination with paclitaxel and carboplatin compared to placebo in combination with paclitaxel and carboplatin. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Motesanib, Paclitaxel and Carboplatin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
401 participants
Where
No sites listed yet
Study dates
Jul 2012to Mar 2015
Phase
Phase 3
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

  • Disease Related:
  • Histologically or cytologically confirmed, Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC) (except diagnosis by sputum cytology only). Adenosquamous histology or an unclear histology subtype containing more than 10% squamous cells was not allowed.
  • No prior chemotherapy, molecularly-targeted therapy, or immunotherapy. Neoadjuvant and post-operative adjuvant therapy except chemotherapy with platinum agent completed 1 year prior to randomization was permitted.
  • Measurable or non-measurable lesion per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 criteria (except non-measurable lesion with malignant effusion only).
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
  • Life expectancy of ≥ 3 months as documented by the Investigator.
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  • Demographic:
  • Must have been 18 years of age or older at the time informed consent was obtained.
  • Laboratory:
  • Hematological function, as follows:
  • Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L.
  • Platelet count ≥ 100 x 10^9/L and ≤ 850 x 10^9/L.
  • Hemoglobin ≥ 9 g/dL.
  • Renal function, as follows:
  • Creatinine clearance (GFR) > 40 mL/min (calculated by Cockcroft-Gault formula).
  • Urinary protein quantitative value of ≤ 30 mg in urinalysis or ≤ 1+ on dipstick unless total quantitative protein was < 500 mg in a 24-hour urine sample.
  • Hepatic function, as follows:
  • Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) or AST < 5 x ULN if liver metastases were present.
  • Alanine aminotransferase (ALT) ≤ 2.5 x ULN or ALT < 5 x ULN if liver metastases were present.
  • Alkaline phosphatase (ALP) ≤ 2.0 x ULN or ALP < 5 x ULN if liver or bone metastases were present.
  • Total bilirubin < 1.5 x ULN.
  • Coagulation function, as follows:
  • Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1 x ULN.
  • International normalized ratio (INR) ≤ 1.5 x ULN.
  • Ethical:
  • Ability to give written informed consent.
  • General:
  • Able to take oral medications.
  • Able to start protocol-directed therapy within 7 days from the date of randomization.

Who cannot join

  • Disease Related:
  • Symptomatic central nervous system metastases. Participants with asymptomatic brain metastases were eligible if definitive therapy had been administered (surgery and/or radiation therapy), there was no planned treatment for brain metastasis, and the participant was clinically stable and off corticosteroids for at least 2 weeks prior to randomization. Participants with asymptomatic brain metastases were also eligible if the participant did not need definitive therapy (surgery and/or radiation therapy) or corticosteroids according to the Investigator's judgement.
  • Palliative radiation therapy:
  • Radiation therapy within 28 days prior to randomization for central (chest).
  • Radiation therapy within 14 days prior to randomization for distant metastatic foci.
  • History of pulmonary hemorrhage or gross hemoptysis (approximately 3 mL of bright red blood or more) within 6 months prior to randomization.
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  • Medications:
  • Prior targeted therapies, including but not limited to:
  • AMG 706, inhibitors of vascular endothelial growth factor (VEGF) (eg, SU5416, SU6668, ZD6474, SU11248, PTK787, AZD2171, AEE-788, sorafenib, bevacizumab), or epidermal growth factor receptor (EGFR) (eg, panitumumab, cetuximab, gefitinib, erlotinib).
  • Any anticoagulation therapy within 7 days prior to randomization. The use of low-dose warfarin (≤ 2 mg daily) or low molecular weight heparin or heparin flushes for prophylaxis against central venous catheter thrombosis was allowed.
  • Known history of allergy or hypersensitivity reaction to paclitaxel or carboplatin.
  • General:
  • History of arterial or venous thrombosis within 12 months prior to randomization.
  • History of bleeding diathesis or bleeding within 14 days prior to randomization.
  • Peripheral neuropathy ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.
  • Clinically significant cardiovascular disease within 12 months of randomization, including myocardial infarction, unstable angina, ≥ Grade 2 peripheral vascular disease, cerebrovascular accident, transient ischemic attack, percutaneous transluminal coronary angioplasty/stent, congestive heart failure or ongoing arrhythmias requiring medication.
  • Any kind of disorder that compromised the ability of the participant to comply with the study procedures.
  • Open wound, ulcer or fracture.
  • Active or any uncontrolled, infection or inflammatory disease requiring systemic treatment ≤ 14 days prior to randomization.
  • Diagnosed interstitial lung disease and/or significant interstitial shadow on the computerized tomography (CT) image.
  • Uncontrolled hypertension as defined by resting blood pressure > 150/90 mmHg despite the use of an antihypertensive.
  • History (past/current) of other primary cancer unless:
  • Curatively resected non-melanomatous skin cancer.
  • Curatively treated cervical carcinoma in situ.
  • Other primary solid tumor curatively treated with no known active disease present and no curative treatment administered for the last 3 years.
  • Surgery:
  • Major surgical procedures within 28 days prior to randomization.
  • Minor surgical procedures within 14 days prior to randomization.
  • Failure to recover from prior surgery.
  • Placement of a central venous access device (including ports and tunneled or non-tunneled catheters) within 3 days in principle prior to randomization.
  • Core needle biopsy within 7 days prior to randomization.
  • Planned elective surgery while on the study treatment.
  • Not recovered from all previous therapies (ie, radiation, surgery and medications). AEs related to previous therapies must have been CTCAE Grade ≤ 1 at Screening or must have resolved to the participant's Baseline level prior to the most recent previous therapy (except alopecia).
  • Participation in therapeutic clinical trials or currently receiving other investigational treatment(s) within 30 days prior to randomization.
  • Pregnant (eg, positive human chorionic gonadotropin [HCG] test-urine or serum) or breast-feeding woman.
  • Any participant not consenting to use adequate contraceptive precautions, from informed consent until 6 months after the last treatment.
  • Known to be human immunodeficiency virus (HIV), hepatitis B surface (HBs) antigen or hepatitis C positive. Participants may have been HBs antigen (-) and HB core antibody (+) and /or HBs antibody (+) with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) (-). If HBs antigen (-) but HBV DNA (+), participant could be enrolled with concomitant antiviral treatment (entecavir or tenofovir). In case of hepatitis C virus (HCV) antibody (+) with HCV ribonucleic acid (-) and/or HCV core antigen (-), participants could be enrolled.
  • Participant with HBs antigen (+) could be enrolled if AST and ALT were within ULN, and HBV DNA level was less than 3.0 Log. The participant must have received concomitant antiviral treatment (entecavir or tenofovir). Participants who were already on antiviral treatment at Screening were not eligible.
  • Known chronic hepatitis.
  • History of any medical or psychiatric condition or laboratory abnormality that, in the opinion of the Investigator, may have increased the risks associated with participation in the study or administration of investigational products (IPs) administration, or may have interfered with the interpretation of the results.
  • Previously randomized to this study.
  • Not available for follow-up assessments or unable to comply with study requirements.

About this study

Official title: A Global Phase 3, Randomized, Placebo Controlled, Double-Blind Trial of AMG 706 in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer (Asian Phase 3 Study)

This study will evaluate progression free survival (PFS), overall survival (OS), objective response rate (ORR), duration of response, and safety of motesanib (AMG706) in combination with paclitaxel and carboplatin compared to placebo in combination with paclitaxel and carboplatin.

Read the detailed description

The drug being tested in this study is called motesanib. Motesanib is being tested in combination with paclitaxel and carboplatin to treat people who have Stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC). This study will look at progression free survival, overall survival, overall response and safety.

The study enrolled 401 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there is an urgent medical need):

  • Motesanib 125 mg + Paclitaxel + Carboplatin
  • Placebo (dummy inactive pill) - this is a tablet that looks like the study drug but has no active ingredient + Paclitaxel + Carboplatin

All participants were asked to take 5 X 25 mg motesanib tablets or placebo at the same time each day throughout the study. All participants received treatment with paclitaxel 200 mg/m^2 intravenous (IV) and carboplatin IV on Day 1 of each 3 week Cycle for up to 6 Cycles. After 6 Cycles participants could continue to receive motesanib or placebo alone for up to 36 months.

This multi-centre trial was conducted worldwide. The overall time to participate in this study was up to 36 months. Participants made multiple visits to the clinic, plus a final visit 30 days after receiving their last dose of study drug for a follow-up assessment.

Being tested
Motesanib, Placebo, Paclitaxel, Carboplatin
Keywords
Drug therapy
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.

  • MotesanibDrug

    Also called AMG 706

    Motesanib (AMG 706) 5 x 25 mg tablets

  • PlaceboDrug

    Motesanib placebo-matching tablets

  • PaclitaxelDrug

    Paclitaxel IV

  • CarboplatinDrug

    Carboplatin IV

Study groups in NCT02629848
Study groupRoleWhat they receive
Motesanib + Paclitaxel + CarboplatinExperimentalMotesanib 125 mg, (5 x 25 mg) tablets, orally, once daily and paclitaxel 200 mg/m^2, intravenous, once on Day 1 and carboplatin at a dose to achieve a target Area Under the Curve (AUC) of 6.0 mg/mL x minute, once on Day 1 of a 3 week Cycle for up to 6 Cycles. After 6 Cycles, motesanib 125 mg, tablets, orally, once daily alone until disease progression, drug intolerability, study withdrawal or death for up to 36 months.
Receives: Drug: Motesanib; Drug: Paclitaxel; Drug: Carboplatin
Placebo + Paclitaxel + CarboplatinPlacebo comparatorMotesanib placebo-matching tablets, orally, once daily and paclitaxel 200 mg/m^2, intravenous, once on Day 1 and carboplatin at a dose to achieve a target AUC of 6.0 mg/mL x minute, once on Day 1 of a 3 week Cycle for up to 6 Cycles. After 6 Cycles, motesanib placebo-matching, tablets, orally, once daily alone until disease progression, drug intolerability, study withdrawal or death for up to 36 months.
Receives: Drug: Placebo; Drug: Paclitaxel; Drug: Carboplatin

What is being measured

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

  1. Progression Free Survival

    PFS was defined as the time from the date of randomization to the date of disease progression per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 or death from any cause, whichever occurred first. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

    Measured: Up to 24 Months

Secondary outcomes (7)

  1. Overall Survival (OS)

    OS was defined as the time from randomization to death (or, where applicable, the censoring date). Participants who had not died or were lost to follow-up by the analysis data cut-off date were censored at their last contact date. Participants who withdrew full consent to participate in the study were censored on the date consent was withdrawn.

    Measured: 6, 12, 18 and 24 months

  2. Objective Response Rate (ORR)

    ORR was defined as the percentage of participants achieving either a complete response (CR) or partial response (PR) per RECIST Version 1.1 criteria. CR= disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. PR= At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the Baseline sum LD.

    Measured: Up to 30 months

  3. Duration of Response (DOR)

    DOR was defined as the time from the date of first response (CR or PR) to disease progression (per RECIST Version 1.1) or death. CR= Disappearance of all target lesions; disappearance of all non-target lesions and normalization of tumor marker level. PR= At least a 30% decrease in the sum of the longest diameter (LD ) of target lesions, taking as reference the Baseline sum LD.

    Measured: Up to 30 months

  4. Percentage of Participants with Treatment Emergent Adverse Events (TEAEs)

    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

    Measured: Up to 30 months

  5. Percentage of Participants with Abnormal Clinical Laboratory Findings

    The percentage of participants with any chemistry or hematology abnormal standard safety laboratory values collected throughout study

    Measured: Up to 30 months

  6. Cmax: Maximum Observed Plasma Concentration for Montesanib and its Metabolite M4

    Maximum Observed Plasma Concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration- time curve.

    Measured: Predose on Day 1 and 1 to 2 hours postdose in Cycles 3 and 5

  7. Cmin: Minimum Observed Plasma Concentration for Montesanib and its Metabolite M4

    Minimum observed plasma concentration (Cmin) is the lowest plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

    Measured: Predose on Day 1 and 1 to 2 hours postdose in Cycles 3 and 5

Timeline

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

  1. First posted14 Dec 2015 (estimated)
  2. Study startJul 2012
  3. Primary completionSep 2014
  4. Study completionMar 2015

Why it stopped: Sponsor decision to terminate the study because the study did not meet the primary endpoint.

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
401 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02629848
Sponsor's protocol ID
TB-AB030103
Other IDs
U1111-1176-7347, JapicCTI-121887
Status last verified
Dec 2015
First submitted
10 Dec 2015
Last updated
14 Dec 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Motesanib, Paclitaxel and Carboplatin in people with Carcinoma, Non-Small-Cell Lung, run by Takeda.

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 29 inclusion and 42 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: stopped early, as of the sponsor's last update on 14 Dec 2015. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 stopped early (reason given: Sponsor decision to terminate the study because the study did not meet the primary endpoint.). Results are not available in the source record.

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?

Progression Free Survival (time frame: Up to 24 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 NCT02629848.

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 Dec 2015.

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