a study in advanced cancers using ramucirumab (ly3009806) and other targeted agents

Conditions: Advanced Cancer; Colorectal Cancer; Mantle Cell Lymphoma

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.


Eligibility criteria:
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