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NSCLCPhase 1/2NCT01100931

A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II)

A Phase 1/2 study testing YM155, Carboplatin and Paclitaxel in people with NSCLC and Solid Tumors, run by National Cancer Institute (NCI) at 1 site 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

Background: Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC, Solid Tumors
What is being tested?
YM155, Carboplatin and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
1 siteUnited States
Study dates
Feb 2010to Dec 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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Response should be YES
  • Phase 1 and 2:
  • Has a signed consent/assent been obtained by the patient or parent/legal guardian?
  • Is a male or female greater than or equal to 18 years old?
  • If patient has brain metastases, is it asymptomatic and does not require steroids or antiepileptic mediations?
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky > 60%)?
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  • Has adequate bone marrow, renal, and hepatic function:
  • Absolute neutrophil count (ANC) greater than or equal to 1,500/m^3?
  • Hemoglobin greater than or equal to 10.0g/dl?
  • Platelets greater than or equal to 100,000/m^3?
  • Has adequate renal function defined as serum creatinine < upper limit of normal (ULN) or calculated creatinine clearance > 60 mL/min?
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times ULN?
  • Total bilirubin less than or equal to 1.5 times ULN (in patients with evidence of Gilberts disease, elevated bilirubin should not be related to tumor or other liver diseases and should be less than or equal 2 times upper limit of normal)?
  • Has negative human immunodeficiency virus (HIV) test?
  • If female, has negative pregnancy test?
  • Both male and female patients are willing to consent to using effective contraception (hormonal, barrier method or abstinence) prior to study entry, while on treatment and at least 3 months thereafter?
  • Phase 1 only:
  • Has recurrent or advanced cancer for whom standard therapy offers no curative potential and also for patients for whom the carboplatin/paclitaxel regimen is considered standard of care?
  • Has received no more than one previous chemotherapy regimen?
  • Has evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria?
  • Phase 2 only:
  • Has histological or cytological evidence of non small cell lung cancer?
  • Has evidence of metastatic disease or stage IIIB non small cell lung cancer (NSCL) with pleural effusion is required?
  • Has no prior chemotherapy for advanced lung cancer?
  • Note: Patients who received adjuvant or neo-adjuvant chemotherapy more than 12 months prior will be eligible?
  • Has 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 or as > 10 mm with spiral computed tomography (CT) scan?

Who cannot join

  • Response should be NO
  • Has any of the following within 6 months prior to study enrollment: myocardial infarction, unstable angina pectoris or uncontrolled angina pectoris, uncontrolled hypertension that is not controllable with antihypertensives, coronary/peripheral artery bypass graft, New York Heart Association (NYHA) class III or IV congestive heart failure, clinically significant peripheral vascular disease (Grade II or greater).
  • Has history of stroke or transient ischemic attack within 6 months?
  • Has history of pulmonary embolism, deep venous thrombosis or other thrombo-embolic event within 6 months?
  • Has psychiatric or neurologic illness that would limit compliance with study requirements?
  • Has severe active infection within 14 days requiring use of intravenous antibiotics before beginning treatment?
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  • Has received any other investigational agents within 30 days of the start of treatment?
  • Has history of an active malignancy unless curatively treated and risk of recurrence of < 5% at five years, with the exception of:
  • Adequately treated in situ carcinoma of the cervix
  • Non-melanomatous skin cancers (basal or squamous cell)?
  • Has history of severe hypersensitivity reaction to compounds of similar chemical or biologic composition to carboplatin, paclitaxel, or medicines of similar composition to YM155?
  • Has history of a major surgical procedure, open biopsy, or a significant traumatic injury within 14 days prior to commencing treatment, or the anticipation of the need for a major surgical procedure during the course of the study?
  • Has other serious illness, medical condition or significant laboratory abnormality that may cause undue risk for the subject's safety, inhibit protocol participation, or interference with interpretation of study results, and in the judgment of the investigator would make the subject inappropriate for entry into this study?
  • Phase 2 only: Has mixed tumor of any histology including small cell lung cancer?

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Background:

  • Carboplatin-paclitaxel is a commonly used chemotherapy combination for advanced non-small-cell lung carcinoma (NSCLC) and other solid tumors. In a randomized clinical trial, the combination of carboplatin, paclitaxel, and the additional chemotherapy drug bevacizumab had a better response rate and survival compared to carboplatin and paclitaxel alone. However, this trial treated only patients with a specific diagnosis and treatment risks. Further research is needed to determine whether this combination is useful for other diagnoses.
  • YM155 is a drug that targets a type of chemical often found in cancer cells. It has been investigated in several phase I and phase II clinical trials, and it has been shown to be well tolerated and moderately effective in treating advanced NSCLC in patients who had not responded well to one or two standard treatments.
Read more

Objectives:

  • To determine the efficacy of the combination of carboplatin, paclitaxel, and YM155 in the treatment of non-small-cell lung cancer.

Eligibility:

  • Individuals 18 years of age and older who have been diagnosed with advanced non-small-cell lung carcinoma or other solid tumors for which standard therapy is not likely to be effective.

Design:

  • Before the start of the study, participants will be screened with a medical history, blood tests, imaging scans of the affected areas, tumor biopsies, and other tests as directed by the study doctors.
  • Participants will be treated for six 21-day cycles, or 18 weeks of treatment. Each cycle will include blood tests and imaging studies as required.
  • On day 1 of each cycle, participants will receive an infusion of paclitaxel and carboplatin, followed by a 4-day infusion of YM155 (through a portable electronic infusion pump).
  • Participants will have a computed tomography scan or other imaging every other cycle (approximately every 6 weeks) to determine whether the therapy is affecting the cancer site.
  • After the sixth cycle, participants will return for follow-up visits at least every 3 months, and will be asked to remain in contact with the researchers to allow further study of the long-term effects of the treatment.
Read the detailed description

Background:

  • Treatment with platinum-based doublet chemotherapy results in a median survival of 7 to 10 months in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC).
  • Carboplatin-paclitaxel is a commonly used regimen in advanced NSCLC and other solid tumors. In a randomized clinical trial carboplatin, paclitaxel plus bevacizumab resulted in improved efficacy (response rate and survival) compared to carboplatin and paclitaxel alone but only patients with non-squamous histology and who were considered low risk of bleeding were treated. Improvement of survival was not confirmed in another randomized study with a different chemotherapy backbone.
  • Novel treatment strategies need to be developed for advanced NSCLC.
  • YM155 is a transcriptional inhibitor of survivin, an inhibitor of apoptosis protein. Pre-clinical activity of YM155 has been observed in several solid tumors, including NSCLC models and synergy was observed in combination with chemotherapeutic drugs, including carboplatin and paclitaxel.
  • YM155 has been investigated in several phase I and phase II clinical trials and it has been shown to be well tolerated with the most common toxicities reported as being reversible and of grades 1 -2 in severity. In addition, as a monotherapy YM155 alone has shown modest antitumor activity in a phase II trial in advanced NSCLC in patients who had failed one or two prior chemotherapy lines.

Primary Objectives:

  • In the Phase I portion of the study the primary objective will be to determine a safe and tolerable phase II dose of YM155 based upon dose limiting toxicities (DLTs) when YM155 is administered over 72 hours by continuous intravenous infusion (CIVI) every 3 weeks in combination with paclitaxel and carboplatin.
  • In the Phase II portion of the study the primary objective will be to determine the objective response rate (ORR = partial response (PR)+ complete response (CR)) of YM155 in combination with carboplatin and paclitaxel in the first line treatment of patients with advanced NSCLC.

Secondary Objectives:

  • In the Phase I portion of the study the secondary objective will be to determine the preliminary activity of the combination regimen based upon response rate as measured by response evaluation criteria in solid tumors [RECIST].
  • In the Phase II portion of the study the secondary objectives will be to determine the median progression free survival (PFS), median overall survival (OS) and safety and tolerability of this combination regimen in this patient population.
  • To assess expression of particular genes on the pretreatment tumor and pre/post treatment serum samples to evaluate the treatment effects and correlate them with clinical outcome.

Eligibility:

Phase I

  • The phase I portion of the trial will be open to all patients with recurrent or advanced cancer (NSCLC and other solid tumors) for whom standard therapy offers no curative potential and also in patients for whom the carboplatin / paclitaxel regimen is considered standard of care. Patients should have received no more than one previous chemotherapy regimen.

Phase II

  • Pathologically confirmed stage IIIB (malignant pleural effusion) or intravenous (IV) or recurrent NSCLC.
  • No previous chemotherapy for advanced lung cancer.
  • Adequate organ and bone marrow function.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Design:

  • Open label phase I/II trial
  • Following a Simon two-stage optimal design
Conditions
NSCLC, Solid Tumors
Being tested
YM155, Carboplatin, Paclitaxel
Keywords
NSCLC, Solid Tumors, YM155, Survivin, Non Small-Cell Lung Cancer, Solid Tumor
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.

  • YM155Drug

    Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).

    Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.

  • CarboplatinDrug

    Also called Paraplatin

    Area under curve (AUC) of 6 intravenous on day 1

  • PaclitaxelDrug

    Also called Taxol

    200 mg/m^2 intravenous on day 1

Study groups in NCT01100931
Study groupRoleWhat they receive
YM155 in Solid TumorsExperimentalPhase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days). Phase II: 10 mg/m^2 (MTD)intravenous infusion over 72 hours every 21 days.
Receives: Drug: YM155; Drug: Carboplatin; Drug: Paclitaxel

What is being measured

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

  1. Phase 1 Safe and Tolerable Phase 2 Dose.

    Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).

    Phase 2 dose is based upon dose limiting toxicities experienced during cycle 1.

    Measured: 1 year

  2. Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)).

    Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: up to 18 weeks

  3. Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

    Measured: 31.5 months

Timeline

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

  1. First posted9 Apr 2010 (estimated)
  2. Study startFeb 2010
  3. Primary completionDec 2012
  4. Study completionDec 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01100931
Sponsor's protocol ID
100051
Other IDs
10-C-0051
Status last verified
Sep 2015
First submitted
8 Apr 2010
Last updated
19 Oct 2015
Data monitoring committee
No

Publications

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

    PubMed 17237035

  • Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH; Eastern Cooperative Oncology Group. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):92-8. doi: 10.1056/NEJMoa011954.

    PubMed 11784875

  • Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr, Olak J, Stover D, Strawn JR, Turrisi AT, Somerfield MR; American Society of Clinical Oncology. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol. 2004 Jan 15;22(2):330-53. doi: 10.1200/JCO.2004.09.053. Epub 2003 Dec 22. No abstract available.

    PubMed 14691125

  • Kelly RJ, Thomas A, Rajan A, Chun G, Lopez-Chavez A, Szabo E, Spencer S, Carter CA, Guha U, Khozin S, Poondru S, Van Sant C, Keating A, Steinberg SM, Figg W, Giaccone G. A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013 Oct;24(10):2601-2606. doi: 10.1093/annonc/mdt249. Epub 2013 Jul 14.

    PubMed 23857959

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing YM155, Carboplatin and Paclitaxel in people with NSCLC and Solid Tumors, run by National Cancer Institute (NCI) at 1 site 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 26 inclusion and 14 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 19 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 4 Apr 2013). 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?

Phase 1 Safe and Tolerable Phase 2 Dose. (time frame: 1 year). The study lists 3 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 NCT01100931, which also lists 4 linked publications.

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 19 Oct 2015; AzTrials last refreshed its copy on 7 Nov 2026.

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