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Breast CancerPhase 2NCT01234402

Study of Icrucumab (IMC-18F1) or Ramucirumab Drug Product (DP) in Combination With Capecitabine or Capecitabine on Previously Treated Breast Cancer Patients

A Phase 2 study testing Ramucirumab DP, IMC-18F1 and Capecitabine in people with Breast Cancer, run by Eli Lilly and Company at 23 sites in 2 countries.

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

An open-label, multicenter, randomized, Phase 2 trial in which participant with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or Icrucumab (IMC-18F1) administered on an every-21-day cycle (in combination with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Ramucirumab DP, IMC-18F1 and Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
23 sitesin 2 countries
Study dates
Mar 2011to Jul 2017
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 or cytologically confirmed breast cancer which at the time of study entry is either Stage III disease not amenable to curative therapy or Stage IV disease
  • Has measurable or nonmeasurable disease
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  • Has received prior anthracycline therapy
  • Has received prior taxane therapy
  • Participants with human epidermal growth factor receptor-2 (HER2) positive disease must have progressed on or following trastuzumab
Show all 17Show fewer
  • Participants with hormone receptor-positive disease must have progressed on or following hormone therapy
  • Has received ≤ 3 prior chemotherapy regimens in any setting (a regimen is defined as any agent[s] that has been administered for more than 1 cycle; sequential neoadjuvant/adjuvant treatment is considered 1 regimen)
  • Has completed any prior radiotherapy ≥ 4 weeks prior to randomization
  • Has completed any prior hormonal therapy ≥ 2 weeks prior to randomization
  • Has adverse events (AEs) that have resolved to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v 4.0) from all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy,or hormonal therapy
  • Has adequate hematologic, coagulation, hepatic and renal function
  • Does not have:
  • cirrhosis at a level of Child-Pugh B (or worse) or
  • cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis and requiring ongoing treatment with diuretics and/or paracentesis
  • Has urinary protein is ≤ 1+ on dipstick or routine urinalysis; if urine protein ≥ 2+, a 24-hour urine collection must demonstrate < 1000 mg of protein in 24 hours to allow participation in the study
  • Agrees to use adequate contraception during the study period and for 12 weeks after the last dose of study medication

Who cannot join

  • Has a concurrent active malignancy other than adequately treated nonmelanomatous skin cancer, curatively treated cervical carcinoma in situ, or other noninvasive carcinoma or in situ neoplasm. A participant with previous history of malignancy is eligible, provided that there has been a disease-free interval for > 3 years
  • Has a known sensitivity to capecitabine, any of its components, or other drugs formulated with polysorbate 80
  • Has a known sensitivity to 5-fluorouracil (5-FU)
  • Has a known dihydropyrimidine dehydrogenase deficiency
  • Has received prior capecitabine treatment for advanced breast cancer
  • Has received investigational therapy within 2 weeks prior to randomization
Show all 23Show fewer
  • Has received bevacizumab within 4 weeks prior to randomization
  • Has received more than 1 prior antiangiogenic agent for breast cancer
  • Has a known sensitivity to agents of similar biologic composition as ramucirumab DP or Icrucumab (IMC-18F1), or other agents that specifically target vascular endothelial growth factor (VEGF)
  • Has an acute/subacute bowel obstruction or history of chronic diarrhea requiring ongoing medical intervention
  • Has a history of uncontrolled hereditary or acquired bleeding or thrombotic disorders
  • Has experienced a Grade ≥ 3 bleeding event within 3 months prior to randomization
  • Is receiving prophylactic or therapeutic anticoagulation with warfarin or any other oral anticoagulant
  • Has an uncontrolled intercurrent illness, including, but not limited to uncontrolled hypertension, symptomatic anemia, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or poorly controlled cardiac arrhythmia, psychiatric illness/social situations, or any other serious uncontrolled medical disorder in the opinion of the investigator
  • Has experienced any arterial thrombotic or thromboembolic events, including, but not limited to myocardial infarction, transient ischemic attack, or cerebrovascular accident within 6 months prior to randomization
  • Has brain metastases, uncontrolled spinal cord compression, or leptomeningeal disease
  • Has an ongoing or active infection requiring parenteral antibiotic, antifungal, or antiviral therapy
  • Has received a prior allogeneic organ or tissue transplantation
  • Has undergone major surgery within 4 weeks prior to randomization, or subcutaneous venous access device placement within 7 days prior to randomization
  • Has had a serious nonhealing wound, ulcer, or bone fracture within 4 weeks prior to randomization
  • Has known HIV or AIDS infection
  • Has an elective or planned major surgery to be performed during the course of the trial
  • Participant is pregnant or lactating

Trial locations and contacts

23 sites in 2 countries.

23 sites in 2 countries

United States20 sites

  • ImClone Investigational Site

    Atlanta, Georgia, 30322

  • ImClone Investigational Site

    Augusta, Georgia, 30912

  • ImClone Investigational Site

    Baton Rouge, Louisiana, 70809

  • ImClone Investigational Site

    Chicago, Illinois, 60611

  • ImClone Investigational Site

    Cincinnati, Ohio, 45242

  • ImClone Investigational Site

    Columbus, Ohio, 43219

  • ImClone Investigational Site

    Dallas, Texas, 75390

  • ImClone Investigational Site

    Indianapolis, Indiana, 46202

  • ImClone Investigational Site

    Jacksonville, Florida, 32224

  • ImClone Investigational Site

    Los Angeles, California, 90033

  • ImClone Investigational Site

    Morgantown, West Virginia, 26506

  • ImClone Investigational Site

    New York, New York, 10021

  • ImClone Investigational Site

    Richmond, Virginia, 23230

  • ImClone Investigational Site

    Salt Lake City, Utah, 84106

  • ImClone Investigational Site

    San Antonio, Texas, 78229

  • ImClone Investigational Site

    Scottsdale, Arizona, 85259

  • ImClone Investigational Site

    Spokane, Washington, 99208

  • ImClone Investigational Site

    Stony Brook, New York, 11794

  • ImClone Investigational Site

    The Bronx, New York, 10461

  • ImClone Investigational Site

    Washington, North Carolina, 27889

Other trials in United States

Canada3 sites

  • ImClone Investigational Site

    Calgary, Alberta, T2N 4N2

  • ImClone Investigational Site

    Edmonton, Alberta, T6G 1Z2

  • ImClone Investigational Site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Ramucirumab (IMC-1121B) Drug Product or Icrucumab (IMC-18F1) in Combination With Capecitabine or Capecitabine Monotherapy, in Unresectable, Locally Advanced or Metastatic Breast Cancer Patients Previously Treated With Anthracycline and Taxane Therapy

An open-label, multicenter, randomized, Phase 2 trial in which participant with unresectable, locally advanced or metastatic breast cancer who have been previously treated with anthracycline and taxane therapy receive ramucirumab DP or Icrucumab (IMC-18F1) administered on an every-21-day cycle (in combination with oral capecitabine therapy; capecitabine is administered twice a day on Days 1-14 of each cycle). Approximately 150 participants will be randomized in a 1:1:1 ratio to either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine (Arm A and Arm B, respectively) or capecitabine monotherapy (Arm C). Randomization will be stratified by triple-negative receptor status (estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor-2 [HER2/neu]-negative) (yes/no) and receipt of prior antiangiogenic therapy.

Treatment with the study medication(s) will continue until disease progression, the development of unacceptable toxicity, noncompliance or withdrawal of consent by the participant, or investigator decision. Capecitabine dose reductions in the setting of significant myelosuppression, hand-and-foot syndrome, or diarrhea will be required.

Conditions
Breast Cancer
Being tested
Ramucirumab DP, IMC-18F1, Capecitabine
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

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

  • Ramucirumab DPBiological

    Also called IMC-1121B, LY3009806

    10 mg/kg I.V.

    Day 1 of every-21-day cycle

  • IMC-18F1Biological

    Also called Icrucumab, LY3012212

    12 mg/kg I.V.

    Days 1 and 8 of every-21-day cycle

  • CapecitabineDrug

    1000 mg/m^2 orally

    Twice a day for 14 days

Study groups in NCT01234402
Study groupRoleWhat they receive
Ramucirumab DP + CapecitabineExperimentalCycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
Receives: Biological: Ramucirumab DP; Drug: Capecitabine
Icrucumab + CapecitabineExperimentalCycles repeat until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
Receives: Biological: IMC-18F1; Drug: Capecitabine
Capecitabine*Active comparatorCrossover Study: * At the discretion of the investigator, participants will be eligible to receive either ramucirumab DP or Icrucumab (IMC-18F1) in combination with capecitabine, after radiographic disease progression while on capecitabine. The investigator will decide which investigational product will be given. Cycles repeat every 21 days until disease progression, the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the participant.
Receives: Drug: Capecitabine

What is being measured

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

  1. Progression-Free Survival (PFS)

    PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) and the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up, or had missed 2 or more scheduled tumor assessments were censored at the day of their last adequate tumor assessment.

    Measured: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)

Secondary outcomes (12)

  1. Overall Survival (OS)

    Overall survival is defined as the time from the date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS will be censored on the last date the participant is known to be alive.

    Measured: From Date of Randomization until Death Due to Any Cause (Up To 160 weeks)

  2. Percentage of Participants With Objective Response Rate (ORR)

    The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm and the appearance of ≥1 new lesions was progression.

    Measured: From Date of Randomization until Disease Progression/Recurrence (Up to 97 weeks)

  3. Duration of Response

    Duration of response is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date that the criteria for progressive disease (PD) is met (taking as a reference for PD that smallest measurement recorded since the treatment started), or death, is objectively documented.CR was defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 mm. PR was defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter.PD defined as ≥20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Sum must also have demonstrated an absolute increase of ≥5 mm, or the appearance of 1 or more new lesions was considered progression.

    Measured: From Date of CR, PR until Disease Progression or Death Due to Any Cause (Up To 97 weeks)

  4. Number of Participants With Adverse Events (AEs)

    Adverse event (AE) will be regarded as treatment-emergent if onset date occurs any time on or after the administration of the first dose of study treatment up to 30 days after the last dose of study treatment (or up to any time if related to study treatment); or it occurs prior to first dose date and worsens while on therapy or up to 30 days after the last dose of study treatment (or up to any time if related to study treatment).

    A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

    Measured: Up To 160 Weeks

  5. Number of Participants With Serious Adverse Events (SAEs)

    SAE was defined as any untoward medical occurrence that at any dose:

    Resulted in death; Was life-threatening; Required inpatient hospitalization or caused prolongation of existing hospitalization; Resulted in persistent or significant disability/incapacity; Was a congenital anomaly/birth defect; Required intervention to prevent permanent impairment/damage; Was an important medical event (defined as a medical event that may not have been immediately life-threatening or resulted in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention to prevent one of the other serious outcomes listed in the definition above).

    A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.

    Measured: Up To 160 Weeks

  6. Maximum Concentration (Cmax) Ramucirumab Drug Product (DP) or Icrucumab

    Measured: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

  7. Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab

    Minimum Concentration (Cmin) Ramucirumab Drug Product (DP) or Icrucumab.

    Measured: Cycle 2,4,6,8,0,12,14,16,18,22: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

  8. Area Under the Concentration Versus Time Curve From Time Zero to Infinity of Ramucirumab or Icrucumab

    Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity of Ramucirumab and Icrucumab.

    Measured: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

  9. Terminal Half-life (t½) of Ramucirumab or Icrucumab

    Terminal half-life (t½) of Ramucirumab and Icrucumab.

    Measured: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

  10. Clearance (Cl) of Ramucirumab or Icrucumab

    Clearance (Cl) of Ramucirumab and Icrucumab.

    Measured: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

  11. Volume of Distribution at Steady State (Vss) of Ramucirumab or Icrucumab

    Volume of Distribution at Steady State (Vss) of Ramucirumab and Icrucumab.

    Measured: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

  12. Number of Participants With Anti-Ramucirumab and Anti-Icrucumab Antibodies

    Measured: Cycle 1: Pre-infusion, 1h, 48h, 72h, 168, 336h post infusion

Timeline

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

  1. First posted4 Nov 2010 (estimated)
  2. Study startMar 2011
  3. Primary completionOct 2013
  4. Study completionJul 2017

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
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01234402
Sponsor's protocol ID
13944
Other IDs
CP20-0903, I4Y-IE-JCDD
Status last verified
Jul 2019
First submitted
3 Nov 2010
Last updated
14 Aug 2019
Data monitoring committee
No
Individual data sharing
Yes: Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com. This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Publications

  • Vahdat LT, Layman R, Yardley DA, Gradishar W, Salkeni MA, Joy AA, Garcia AA, Ward P, Khatcheressian J, Sparano J, Rodriguez G, Tang S, Gao L, Dalal RP, Kauh J, Miller K. Randomized Phase II Study of Ramucirumab or Icrucumab in Combination with Capecitabine in Patients with Previously Treated Locally Advanced or Metastatic Breast Cancer. Oncologist. 2017 Mar;22(3):245-254. doi: 10.1634/theoncologist.2016-0265. Epub 2017 Feb 20.

    PubMed 28220020

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ramucirumab DP, IMC-18F1 and Capecitabine in people with Breast Cancer, run by Eli Lilly and Company at 23 sites in 2 countries.

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 17 inclusion and 23 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 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in United States, Canada. 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 14 Aug 2019). 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?

Progression-Free Survival (PFS) (time frame: From Date of Randomization until Disease Progression or Death Due to Any Cause (Up To 97 weeks)). 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 NCT01234402, 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 Aug 2019.

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