Clinical trial NCT02082210: A Study of Emibetuzumab in Combination With Ramucirumab (LY3009806) in Participants With Advanced Cancer
Official title: A Phase 1b/2 Study of Ramucirumab in Combination With LY2875358 in Patients With Advanced Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Advanced Cancer
Gastric Adenocarcinoma
Gastroesophageal Junction Adenocarcinoma
Hepatocellular Cancer
Renal Cell Carcinoma
Non-Small Cell Lung Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2014-03-10
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.


Eligibility criteria: Inclusion Criteria:

* 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)
* 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.

Exclusion Criteria:

* 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.
* 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

Primary outcomes:
measure: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
timeFrame: Baseline through Cycle 1 (28 day cycle)
measure: Part B: Percentage of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
timeFrame: Baseline through Measured Progressive Disease or Death (Up to 17 months)
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Observed Plasma Concentration (Cmax) of Emibetuzumab
timeFrame: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h, 334h, 335h and 336h Post dose
measure: Part B: Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR) (Disease Control Rate [DCR])
timeFrame: Baseline through Measured Progressive Disease (Up to 17 months)
measure: Part B: Progression Free Survival (PFS)
timeFrame: Baseline to Measured Progressive Disease or Death (Up to 17 Months)
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) From Time Zero to Tlast of Emibetuzumab
timeFrame: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h, 334h, 335h and 336h Post dose
measure: Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of Ramucirumab
timeFrame: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h and 336h Post dose
measure: Number of Participants With Treatment Emergent Anti-Emibetuzumab Antibodies
timeFrame: Baseline through 46 Months
measure: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Ramucirumab
timeFrame: Cycle 1: Day1 Predose, End of infusion, 3 Hours (h), 5h, 8h, 21h, 168h and 336h Post dose
measure: Number of Participants With Treatment Emergent Anti-Ramucirumab Antibodies
timeFrame: Baseline through 46 Months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Nashville
country: United States
facility: Tennessee Oncology PLLC
state: Tennessee
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: