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CancerPhase 2NCT01017731

Study of Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes

A Phase 2 study testing IMC-1121B, Moxifloxacin and Diphenhydramine in people with Cancer and Solid Tumor, run by Eli Lilly and Company at 7 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 purpose of this study is to determine if Ramucirumab (IMC-1121B) causes prolongation of the QT/QTc interval in participants with advanced cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Cancer, Solid Tumor
What is being tested?
IMC-1121B, Moxifloxacin and Diphenhydramine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
68 participants
Where
7 sitesUnited States
Study dates
Nov 2009to May 2014
Phase
Phase 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

  • The participant has histologically documented advanced or metastatic malignant cancer of solid tumor origin which has not responded to standard therapy or for which no standard therapy is available
  • The participant has resolution of adverse events from prior anticancer therapies
  • Performance status of 0 to 2
  • The participant is ≥ 18 years of age
  • The participant is able to provide informed written consent and is amenable to compliance with protocol schedules and testing
  • The participant has adequate liver, kidney, blood, and blood clotting functions as defined in trial entrance criteria
  • The participant agrees to use adequate contraception during the study period and for 8 weeks after the last dose of study treatment

Who cannot join

  • The participant had anticancer therapy within 14 days (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
  • The participant had therapeutic radiotherapy within 14 days prior to entering the study
  • The participant has ongoing side effects ≥ Grade 2 due to prior anticancer therapy
  • The participant has brain or leptomeningeal metastases
  • The participant has a history of uncontrolled or severe cardiac disease
  • The participant has a history of severe congestive heart failure (CHF)
Show all 22Show fewer
  • The participant has a known history of arterial thrombotic events
  • The participant has a known history of significant peripheral arterial disease (PAD)
  • The participant has an implantable pacemaker or automatic implantable cardioverter defibrillator (AICD)
  • The participant has a history of risk factors for ventricular tachycardia or Torsades de pointes (TdP) [for example, family history (parents or siblings) of long QT syndrome], history of fainting, unexplained loss of consciousness, or convulsions
  • The participant has a systolic blood pressure (SBP) of > 150 millimeters of mercury (mmHg) or < 90 mmHg or a diastolic blood pressure (DBP) of < 45 or > 95 mmHg. (Participants with a history of hypertension who are receiving antihypertensive therapy are permitted on study provided blood pressure is within the parameters detailed above)
  • The participant has a heart rate < 50 beats per minute (bpm) or > 100 bpm at rest
  • The participant has a clinically relevant abnormality on the ECG, preventing an accurate measurement of the QT interval
  • The participant is using a medication that is known to prolong the ECG QT interval
  • The participant has a known allergy to any of the treatment components including fluoroquinolone antibiotics
  • The participant has received an investigational new drug or device within 14 days prior to enrollment into this study (excluding placement of an intravenous access device)
  • The participant has undergone major surgery within 28 days prior to enrollment
  • The participant has known human immunodeficiency virus (HIV) infection
  • The participant, if female, is pregnant or lactating
  • The participant is receiving chronic daily treatment with aspirin [> 325 milligrams per day (mg/day)]
  • The participant has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, other noninvasive carcinoma, or in situ neoplasm
  • The participant has psychological, familial, sociological, or geographical conditions which do not permit adequate study follow-up, compliance with the protocol, or signature of Informed Consent

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • ImClone Investigational Site

    Ann Arbor, Michigan, 48109

  • ImClone Investigational Site

    Atlanta, Georgia, 30322

  • ImClone Investigational Site

    Houston, Texas, 77024

  • ImClone Investigational Site

    Metairie, Louisiana, 70006

  • ImClone Investigational Site

    Philadelphia, Pennsylvania, 19111

  • ImClone Investigational Site

    Providence, Rhode Island, 02903

  • ImClone Investigational Site

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Study to Evaluate the Relationship Between Ramucirumab (IMC-1121B) Therapy and Corrected QT (QTc) Interval Changes in Patients With Advanced Cancer

The purpose of this study is to determine if Ramucirumab (IMC-1121B) causes prolongation of the QT/QTc interval in participants with advanced cancer.

Read the detailed description

The primary purpose of this study is to determine if treatment with ramucirumab causes prolongation of the QTc/QT interval in participants with advanced cancer, to assess the safety and tolerability of ramucirumab therapy, and to evaluate the pharmacokinetic (PK) characteristics of ramucirumab

Conditions
Cancer, Solid Tumor
Being tested
IMC-1121B, Moxifloxacin, Diphenhydramine
Keywords
Advanced Solid tumor, Antibodies, Monoclonal, QTc, Metastatic, Malignant
Medical subject headings
Neoplasms, Neoplasm Metastasis

What participants receive

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

  • IMC-1121BBiological

    Also called Ramucirumab, LY3009806

    IMC-1121B (Ramucirumab) 10 mg/kg intravenously (IV) over 60 minutes, once every 3 weeks for minimum of 9 weeks.

  • MoxifloxacinDrug

    Administered orally

  • DiphenhydramineDrug

    Administered IV

Study groups in NCT01017731
Study groupRoleWhat they receive
IMC-1121BExperimentalActive-control participants (first 16 participants) will receive one dose of moxifloxacin orally 7 days before the first treatment with ramucirumab. All participants will undergo triplicate electrocardiogram (ECG) tests (consisting of three individual ECGs performed consecutively within a period of 4 minutes) and vital signs at various times over the trial period. For Cycle 1, all participants will also receive 2 infusions of diphenhydramine before ramucirumab therapy (the first infusion is 1 day before therapy and the second infusion is 15 minutes before therapy). For Cycles 2, 3, and 4, all participants will receive diphenhydramine 15 minutes before ramucirumab therapy. For Cycle 5 and beyond, diphenhydramine infusions before ramucirumab therapy are at the investigator's discretion. Ramucirumab [10 milligrams per kilogram (mg/kg)] intravenously over 60 minutes, once every 3 weeks for minimum of 9 weeks without a break in between.
Receives: Biological: IMC-1121B; Drug: Moxifloxacin; Drug: Diphenhydramine

What is being measured

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

  1. Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants

    All electrocardiogram (ECG) tests were performed in triplicate prior to ramucirumab treatment. QT is the interval between the Q and T waves and QTc is the QT corrected for heart rate using Fridericia's formula: QTc = QT/RR^0.33 where RR is the interval between 2 R waves. Each participant's mean QT/QTc value was calculated for each ECG test during Cycle 3 and compared to his/her mean pretreatment QT/QTc value. The greatest change from baseline during Cycle 3 was reported. QTc prolongation is defined as a QTc exceeding 10 milliseconds (msec) with a lower 90% confidence interval (CI) exceeding 5 msec at any postdose time points per the International Conference on Harmonization (ICH) E14 guidelines for non-thorough QT studies (ICH 2005; ICH 2008). Least squares (LS) mean was calculated using a linear mixed model for repeated measures (MMRM) and adjusted for serum concentration.

    Measured: Baseline, Cycle 3 (1 cycle=21 days)

Secondary outcomes (13)

  1. Number of Participants With Drug-Related Adverse Events (AEs)

    Data presented are the number of participants who experienced treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), Grade 3 or higher TEAEs, or adverse events (AEs) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section.

    Measured: Baseline up to data cut off (approximately 105.6 weeks)

  2. Maximum Concentration (Cmax) During Cycle 1

    Maximum observed concentration of IMC-1121B (ramucirumab) in serum during Cycle 1 (1 cycle=21 days).

    Measured: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]

  3. Maximum Concentration (Cmax) During Cycle 1, Day 4

    Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.

    Measured: Approximately Week 1 (Cycle 1, Day 4)

  4. Maximum Concentration (Cmax) During Cycle 1, Day 8

    Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.

    Measured: Approximately Week 2 (Cycle 1, Day 8)

  5. Maximum Concentration (Cmax) During Cycle 1, Day 15

    Cmax was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 3 for Cmax during Cycle 1.

    Measured: Approximately Week 3 (Cycle 1, Day 15)

  6. Maximum Concentration (Cmax) During Cycle 2

    Cmax was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.

    Measured: Cycle 2 (predose and 1.25 hours postdose)

  7. Maximum Concentration (Cmax) During Cycle 3

    The maximum observed serum concentration of IMC-1121B (ramucirumab) at steady state (Cmax,ss) during Cycle 3 (1 cycle=21 days).

    Measured: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]

  8. Area Under Concentration (AUC) During Cycle 1

    The area under the concentration versus time curve from time 0 to infinity [AUC(0-inf)] is reported during Cycle 1 (1 cycle=21 days).

    Measured: Cycle 1 [2.25 hours (h), 3.25 h, 4.25 h, 72 h, 168 h, 336 h postdose]

  9. Area Under Concentration (AUC) During Cycle 1, Day 4

    AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).

    Measured: Approximately Week 1 (Cycle 1, Day 4)

  10. Area Under Concentration (AUC) During Cycle 1, Day 8

    AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).

    Measured: Approximately Week 2 (Cycle 1, Day 8)

  11. Area Under Concentration (AUC) During Cycle 1, Day 15

    AUC was summarized once per cycle because participants only received 1 dose of IMC-1121B (ramucirumab) per cycle. Refer to secondary outcome measure 9 for AUC during Cycle 1 (Day 1 through Day 15).

    Measured: Approximately Week 3 (Cycle 1, Day 15)

  12. Area Under Concentration (AUC) During Cycle 2, Day 1

    AUC was not calculated due to the sparse pharmacokinetic sampling employed on Cycle 2, Day 1.

    Measured: Approximately Week 1 (Cycle 2, Day 1)

  13. Area Under Concentration (AUC) During Cycle 3

    The area under the concentration versus time curve over the dosing interval at steady state [AUC(tau,ss)] is reported during Cycle 3 (1 cycle=21 days).

    Measured: Cycle 3 [predose and 1.25 hours (h), 2.25 h, 3.25 h, 4.25 h, 72 h, 168 h, 336 h, and 504 h postdose]

Timeline

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

  1. First posted23 Nov 2009 (estimated)
  2. Study startNov 2009
  3. Primary completionApr 2010
  4. Study completionMay 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 2
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
68 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01017731
Sponsor's protocol ID
13915
Other IDs
CP12-0712, I4T-IE-JVBK
Status last verified
May 2015
First submitted
19 Nov 2009
Last updated
10 Jun 2015
Data monitoring committee
No

Publications

  • Olszanski AJ, Smith DC, Camacho LH, Thompson J, Ramalingam SS, Harvey RD, Campos L, Ferry D, Tang S, Gao L, Safran H. Electrocardiographic Characterization of Ramucirumab on the Corrected QT Interval in a Phase II Study of Patients With Advanced Solid Tumors. Oncologist. 2016 Apr;21(4):402-3. doi: 10.1634/theoncologist.2015-0467. Epub 2016 Mar 16.

    PubMed 26984445

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing IMC-1121B, Moxifloxacin and Diphenhydramine in people with Cancer and Solid Tumor, run by Eli Lilly and Company at 7 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 7 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: finished, as of the sponsor's last update on 10 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 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 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 18 Jun 2014). 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?

Change From Baseline to Cycle 3 in QT/Corrected QT (QTc) Interval Prolongation in Participants (time frame: Baseline, Cycle 3 (1 cycle=21 days)). 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 NCT01017731, 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 10 Jun 2015.

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