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Advanced CancerPhase 1/2NCT02082210

A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer

A Phase 1/2 study testing Emibetuzumab and Ramucirumab in people with Advanced Cancer and Gastric Adenocarcinoma, run by Eli Lilly and Company at 4 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 find a recommended schedule and dose range for Emibetuzumab when given with ramucirumab that may be safely given to participants with cancer. In Part A of this study, escalating doses of Emibetuzumab will be given in combination with a fixed dose of ramucirumab to evaluate the safety of… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Emibetuzumab and Ramucirumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
97 participants
Where
4 sitesUnited States
Study dates
7 Mar 2014to 24 Jan 2018
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

  • Participants must have histological or cytological confirmed diagnosis of the following tumor types that is advanced and/or metastatic cancer and must be, in the judgment of the investigator, an appropriate participant for experimental therapy
  • Part A: Any type of solid tumor ("all comer")
  • Part B1: Gastric or Gastroesophageal Junction (GEJ) adenocarcinoma
  • Part B2: Hepatocellular cancer (excluding fibrolamellar carcinoma)
  • Part B3: Renal cell carcinoma (any histology)
  • Part B4: Non-small cell lung cancer (squamous or non-squamous)
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  • Have at least 1 measurable lesion outside of the central nervous system (CNS) whose presence is assessable using standard techniques by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
  • Availability of a tumor sample taken after progression on the most recent line of systemic tumor therapy or willing to undergo a tumor biopsy pre-study treatment.
  • Have a performance status of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale in Part A and ≤ 1 on the ECOG scale in Part B.
  • Have adequate organ function.
  • Routine urinalysis showing ≤1+ protein or protein/creatinine ratio <0.5. For proteinuria ≥2+ or urine protein/creatinine ratio ≥0.5, 24-hour urine must be collected and the level must be <1 gram of protein in 24 hours for subject enrollment.
  • Have discontinued all previous cancer therapies and any agents that have not received regulatory approval for any indication, for at least 21 days or 5 halflives prior to study enrollment, whichever is shorter, and recovered from the acute effects for therapy.
  • Have an estimated life expectancy, in the judgment of the investigator, that will permit the participant to complete 8 weeks (2 cycles) of treatment.
  • Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for at least 3 months following the last dose of study drug. Females with childbearing potential must have had a negative serum pregnancy test 7 days before the first dose of study drug and must not be breast-feeding.

Who cannot join

  • Have serious pre-existing medical conditions (at the discretion of the investigator, such as severe acute or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation).
  • Have a history of hypertensive crisis or hypertensive encephalopathy or current poorly controlled hypertension despite standard medical management.
  • Participant has experienced any arterial thromboembolic event (ATE), including myocardial infarction, unstable angina pectoris, cerebrovascular accident, or transient ischemic attack, within 6 months prior to receiving study drugs.
  • Have a history of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolic event during the 3 months prior to receiving study drugs.
  • Are receiving therapeutic anticoagulation with warfarin, low-molecular weight heparin, or similar agents. Participants receiving prophylactic, low-dose anticoagulation therapy are eligible provided that they are on low-molecular weight heparin or oral factor Xa inhibitors.
  • The participant is receiving chronic therapy with nonsteroidal anti-inflammatory drugs or other antiplatelet agents. Aspirin use at doses up to 325 mg/day is permitted.
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  • Have significant bleeding disorders, vasculitis, or had a significant bleeding episode from the gastrointestinal (GI) tract within 3 months prior to receiving study drugs.
  • Have a history of GI perforation and/or fistulae within 6 months prior to receiving study drugs.
  • Have congestive heart failure (CHF) New York Heart Association class ≥3 or symptomatic or poorly controlled cardiac arrhythmia.
  • Have undergone major surgery within 28 days prior to receiving study drugs.
  • Have a serious or nonhealing wound, peptic ulcer, or bone fracture within 28 days prior to receiving study drugs.
  • Have a known active fungal, bacterial, and/or known viral infection. Hepatocellular cancer participants with chronic viral (B or C) hepatitis are eligible if they retain adequate liver function.
  • Have liver cirrhosis with a Child-Pugh Stage of B or C.
  • Have symptomatic CNS malignancy (with the exception of medulloblastoma) or metastasis.
  • Have corrected QT (QTc) interval of >470 milliseconds on screening electrocardiogram (ECG).
  • Have received previous treatment with ramucirumab or Emibetuzumab, except for participants enrolled in cohort B1 (Gastric or GEJ adenocarcinoma) and B4 (non- small cell lung cancer) who may have received previous ramucirumab treatment.
  • Known hypersensitivity to any of the treatment components of ramucirumab or Emibetuzumab.
  • Have a second primary malignancy that, in the judgment of the investigator and sponsor, may affect the interpretation of results.
  • Are pregnant or breastfeeding.
  • For Part B4 (non-small cell lung cancer) only:
  • The participant has radiologically documented evidence of major blood vessel invasion or encasement by cancer
  • Participants with a history of gross hemoptysis within 2 months prior to study treatment
  • The participant has radiographic evidence of intratumor cavitation, regardless of tumor histology

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114-3117

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Tennessee Oncology PLLC

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase 1b/2 Study of Ramucirumab in Combination With LY2875358 in Patients With Advanced Cancer

The purpose of this study is to find a recommended schedule and dose range for Emibetuzumab when given with ramucirumab that may be safely given to participants with cancer. In Part A of this study, escalating doses of Emibetuzumab will be given in combination with a fixed dose of ramucirumab to evaluate the safety of the combination. After a recommended schedule and dose range of Emibetuzumab and ramucirumab has been established, Part B of the study will confirm safety and to see how well certain tumors respond to the combination of study drugs. The average amount of time on study is expected to be about 6 months.

Being tested
Emibetuzumab, Ramucirumab
Medical subject headings
Liver Neoplasms, Carcinoma, Renal Cell, Carcinoma, Non-Small-Cell Lung

What participants receive

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

  • EmibetuzumabDrug

    Also called LY2875358

    Administered Intravenously (IV)

  • RamucirumabDrug

    Also called LY3009806, IMC-1121B

    Administered Intravenously (IV)

Study groups in NCT02082210
Study groupRoleWhat they receive
Emibetuzumab + Ramucirumab (Part A)ExperimentalPart A: Dose escalation (750mg, 2000mg) of Emibetuzumab administered intravenously (IV), on days 1 and 15 every 28 day cycle in combination with a fixed dose of 8mg/kg ramucirumab administered IV on Days 1 and 15 every 28 day cycle.
Receives: Drug: Emibetuzumab; Drug: Ramucirumab
Emibetuzumab + Ramucirumab (Part B)ExperimentalPart B: Recommended 750mg Emibetuzumab dose from Part A to be administered IV, on days 1 and 15 every 28 day cycle in combination with a fixed dose of 8mg/kg ramucirumab administered IV on Days 1 and 15 every 28 day cycle.
Receives: Drug: Emibetuzumab; Drug: Ramucirumab

What is being measured

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

  1. Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

    DLT is defined as an adverse event during Cycle1 that is possibly, probably, or definitely related to treatment with Emibetuzumab in combination with fixed regimen of Ramucirumab \& fulfills any 1 of the following criterion using NCI CTCAE Version 4.03:

    Grade 3 non-hematological toxicity. Exceptions will be made for:Nausea, vomiting, diarrhea, constipation, or skin rash that persists for ≤3 days following appropriate supportive care intervention. Grade 3 hypertension in which systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg persist <7 days after intensified antihypertensive therapy is initiated.

    Grade 4 hematological toxicity of ≥7 days duration.

    ≥Grade 3 thrombocytopenia with ≥Grade 2 bleeding.

    Any febrile neutropenia.

    Any other significant toxicity deemed by the primary investigator \& Lilly clinical research personnel to be dose-limiting (eg, any toxicity that is possibly related to the study medication that requires the withdrawal of participant from study Cycle1).

    Measured: Baseline through Cycle 1 (28 day cycle)

  2. Part B: Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

    ORR is the percentage of participants achieving a best overall response (BOR) of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

    Measured: Baseline through Measured Progressive Disease or Death (Up to 17 months)

Secondary outcomes (8)

  1. Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Emibetuzumab

    Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Emibetuzumab.

    Measured: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h, 334h, 335h and 336h Post dose

  2. Part B: Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) (Disease Control Rate [DCR])

    DCR is the proportion of participants who exhibit a SD or confirmed CR or PR relative to baseline. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

    Measured: Baseline through Measured Progressive Disease (Up to 17 months)

  3. Part B: Progression Free Survival (PFS)

    PFS was defined as the time from the date of first dose of study drug until first observation of objective (radiographically documented) PD as defined by RECIST v1.1 or death from any cause, whichever comes first. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions.

    Measured: Baseline to Measured Progressive Disease or Death (Up to 17 Months)

  4. Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) From Time Zero to Tlast of Emibetuzumab

    Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) from time zero to tlast of Emibetuzumab.

    Measured: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h, 334h, 335h and 336h Post dose

  5. Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab

    Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab.

    Measured: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h and 336h Post dose

  6. Number of Participants With Treatment Emergent Anti-Emibetuzumab Antibodies

    Participants were considered as treatment-emergent anti drug antibodies (TE ADA) positive if there is a ≥4-fold increase from baseline when ADAs were detected at baseline. If no ADAs were detected at baseline, TE ADA were defined as those with a titer 2 fold (1 dilution) greater than the minimum required dilution (MRD) of the screening assay (1:4 for anti-emibetuzumab antibodies).

    Measured: Baseline through 46 Months

  7. Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Ramucirumab

    Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Ramucirumab.

    Measured: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h and 336h Post dose

  8. Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies

    Participants were considered as treatment-emergent anti drug antibodies (TE ADA) positive if there is a ≥4-fold increase from baseline when ADAs were detected at baseline. If no ADAs were detected at baseline, TE ADA were defined as those with a titer 2 fold (1 dilution) greater than the minimum required dilution (MRD) of the screening assay (1:10 for anti-ramucirumab antibodies).

    Measured: Baseline through 46 Months

Timeline

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

  1. First posted10 Mar 2014 (estimated)
  2. Study start7 Mar 2014
  3. Primary completion5 Dec 2017
  4. Study completion24 Jan 2018

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
97 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02082210
Sponsor's protocol ID
15246
Other IDs
I4C-MC-JTBF
Status last verified
Mar 2018
First submitted
6 Mar 2014
Last updated
19 Dec 2020
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Emibetuzumab and Ramucirumab in people with Advanced Cancer and Gastric Adenocarcinoma, run by Eli Lilly and Company at 4 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 14 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 19 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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 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 19 Dec 2020). 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?

Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs) (time frame: Baseline through Cycle 1 (28 day cycle)). The study lists 2 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 NCT02082210.

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 Dec 2020.

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