A Study in Advanced Cancers Using Ramucirumab (LY3009806) and Other Targeted Agents

Phase 1

Completed

• Conditions: Advanced Cancer; Colorectal Cancer; Mantle Cell Lymphoma
• Interventions: Drug: Ramucirumab; Drug: Abemaciclib; Drug: Merestinib

• Registration Number: NCT02745769
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of this study is to evaluate the safety of ramucirumab in combination with other targeted agents in participants with advanced cancers.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-18
• Study First Submitted QC: 2016-04-18
• Study First Posted: 2016-04-20
• Study Start: 2016-10-21
• Primary Completion: 2018-11-05
• Study Completion: 2019-01-22
• Status Verified: 2019-03-01
• Last Update Submitted: 2019-03-02
• Last Update Posted: 2019-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

• Study Arm 1:

  • histopathologically confirmed advanced or metastatic colorectal cancer, excluding primary tumors of appendiceal origin
  • have at least 1 measurable lesion assessable by radiological imaging. Tumor lesions located in a previously irradiated area are considered measureable if progression has been demonstrated in such lesions
  • have received prior second-line treatment with oxaliplatin and/or irinotecan, and no other licensed/standard-of-care therapies are available. If the participant has RAS wild type colorectal cancer, he or she also must have received prior treatment with an epidermal growth factor receptor monoclonal antibody

• Study Arm 2

  • pathologically confirmed mantle cell lymphoma (MCL), with (a) measurable nodal disease on positron emission tomography computed tomography (PET-CT) per Lugano classification. Prior to enrollment, pathology must be reviewed and confirmed at the investigational site where the participant is entered
  • have MCL that relapsed after or is refractory to (a) first-line combination chemotherapy with or without stem cell transplant and (b) at least 1 other locally available therapy
  • provide a newly obtained tumor tissue sample. Tumor tissue biopsies may be taken by surgical resection, core needle biopsy, or fine needle biopsy

• All Study Arms:

  • have not received previous systemic therapy (including investigational agents) targeting programmed cell death protein 1 (PD-1)/ PD-1 ligand (PDL 1) or PD-1/PDL-2 signaling pathways. Prior therapy with other immune checkpoint inhibitors, including but not limited to, anti-CD137 antibody or anticytotoxic T-lymphocyte-associated antigen-4 antibody, is not permitted
  • have adequate organ function
  • are, in the judgment of the investigator, appropriate candidates for experimental therapy after available standard therapies have failed to provide clinical benefit
  • have discontinued all previous treatments for cancer and recovered from the acute effects of therapy, other than less than or equal to Grade 2 neuropathy or nonserious and nonlife-threatening toxicities such as alopecia, altered taste, and nail changes
  • have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale
  • men and women must agree to the use an effective method of contraception during the study and for at least 3 months post last dose of study drug administration. Women of child-bearing potential must have negative serum and urine pregnancy tests at screening and during each treatment cycle, respectively

Exclusion Criteria

• Study Arm 1

  • have a serious illness or medical condition including, but not limited to, the following: active or uncontrolled clinically serious infection; inadequate biliary drainage with evidence of unresolved biliary obstruction

• Study Arm 2

  • have a serious illness or medical condition including, but not limited to, the following: active or uncontrolled clinically serious infection, including chronic viral hepatitis

• All Arms:

  • have prior or concurrent malignancies, inclusive of hematologic, primary brain tumor, sarcoma, and other solid tumors, unless in complete remission with no therapy for a minimum of 5 years
  • have active gastrointestinal (GI) disease characterized by inflammatory bowel disease, malabsorption syndrome, or frequent Grade 2 or more diarrhea
  • are pregnant or breastfeeding
  • have previously documented brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression
  • have experienced any of the following: a major surgical procedure, significant traumatic injury, non-healing wound, peptic ulcer, or bone fracture less than or equal to 28 days prior to enrollment, or placement of a subcutaneous venous access device less than or equal to 7 days prior to the first dose of study treatment unless the procedure is of low risk of bleeding in the judgment of the investigator
  • have an elective or a planned major surgery during the course of the trial
  • have a known allergy or hypersensitivity reaction to any of the treatment components
  • have uncontrolled hypertension
  • have experienced any arterial thromboembolic event within 6 months prior to enrollment
  • have experienced any Grade 3 or 4 venous thromboembolic event that is considered by the investigator to be life threatening or that is symptomatic and not adequately treated by anticoagulation therapy, within 6 months prior to enrollment
  • have a history of GI perforation and/or fistulae within 6 months prior to enrollment
  • have experienced any bleeding episode considered life-threatening, or any Grade 3 or 4 GI/variceal bleeding episode in the 3 months prior to enrollment requiring transfusion or endoscopic or operative intervention
  • have congestive heart failure or poorly controlled cardiac arrhythmia per New York Heart Association Class II-IV heart disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ramucirumab + Abemaciclib	Abemaciclib	Ramucirumab IV on day 1 and day 15 in combination with abemaciclib orally twice a day over a 28 day cycle. Participants receiving benefit may continue until disease progression. On June 21st 2017 the Ramucirumab + Abemaciclib arm was cancelled with no participants enrolled.
Ramucirumab + Merestinib	Ramucirumab	Ramucirumab intravenously (IV) on day 1 and day 15 in combination with merestinib orally once a day over a 28 day cycle. Participants receiving benefit may continue until disease progression.
Ramucirumab + Abemaciclib	Ramucirumab	Ramucirumab IV on day 1 and day 15 in combination with abemaciclib orally twice a day over a 28 day cycle. Participants receiving benefit may continue until disease progression. On June 21st 2017 the Ramucirumab + Abemaciclib arm was cancelled with no participants enrolled.
Ramucirumab + Merestinib	Merestinib	Ramucirumab intravenously (IV) on day 1 and day 15 in combination with merestinib orally once a day over a 28 day cycle. Participants receiving benefit may continue until disease progression.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)	Cycle 1 (28 days)

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab, Merestinib and Abemaciclib	Predose Cycle 1 Day 1 through Predose Cycle 6 Day 1 (28 day cycles)
Proportion of Participants Who Exhibit Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]	Baseline through Measured Progressive Disease or Death (Estimated up to 24 months)
Progression Free Survival (PFS)	Baseline through Measured Progressive Disease or Death (Estimated up to 24 months)

Trial Locations

Locations (3)

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

UAB Comprehensive Cancer Center; 🇺🇸 Birmingham, Alabama, United States

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.; 🇬🇧 London, United Kingdom