Phase II Nivolumab and Ramucirumab for Patients With Previously-Treated Mesothelioma

NCT03502746 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCRN-LUN15-299
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

This study will evaluate the combination of Nivolumab and Ramucirumab in patients with previously-treated mesothelioma.

Conditions

Mesothelioma, Malignant

Outcome Measures

Primary Outcomes (1)

• Response Rate

  Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) \>= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. Response rate will be defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1.

  Up to a maximum of 23 months

Secondary Outcomes (3)

• Adverse Event Assessment

  AE had been recorded from time of consent until 100 days after discontinuation of study drug or until a new anti-cancer treatment starts, whichever occurs first; up to a maximum of 28 months.

• Progression-free Survival (PFS)

  Time of treatment start until the criteria for disease progression or death, up to a maximum of 23 months.

• Overall Survival

  Time of treatment start until death or date of last contact, up to a maximum of 32 months.

Study Arms (1)

Nivolumab + Ramucirumab

EXPERIMENTAL

Nivolumab 240mg IV + Ramucirumab 8mg/kg IV

Drug: Nivolumab; Drug: Ramucirumab

Interventions

Nivolumab DRUG

Nivolumab 240mg, IV over 30 minutes.

Also known as: Opdivo

Nivolumab + Ramucirumab

Ramucirumab DRUG

8mg/kg, IV over 60 minutes.

Also known as: Cyramza

Nivolumab + Ramucirumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female ≥ 18 years of age at time of consent.
• Histologically-confirmed malignant mesothelioma not amenable to curative surgery and who have received at least one pemetrexed-containing chemotherapy regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• total bilirubin \< 1.5 mg/dL (25.65 μmol/L) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 mg/dL (except subject with Gilbert's Syndrome, who can have total bilirubin \< 3.0 mg/dl)
• aspartate aminotransferase (AST) ≤ 3 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• alanine aminotransferase (ALT) ≤ 3 × ULN or ≤ 5 × ULN for subjects with known hepatic metastases
• hemoglobin ≥ 8 g/dL, subjects requiring transfusion will not be eligible to start study
• absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• platelet count ≥ 100 × 109/L
• serum creatinine ≤1.5 times the ULN, or creatinine clearance (measured via 24-hour urine collection) ≥40 mL/minute (that is, if serum creatinine is \>1.5 times the ULN, a 24-hour urine collection to calculate creatinine clearance must be performed)
• subject's urinary protein is ≤1+ on dipstick or routine urinalysis (UA; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection for protein must demonstrate \<1000 mg of protein in 24 hours to allow participation in this protocol)
• INR \< 1.5, and a partial thromboplastin time (PTT) (PTT/aPTT) \< 1.5 x ULN (unless receiving anticoagulant therapy)
• Subjects on full-dose anticoagulation must be on a stable dose (minimum duration 14 days) of oral anticoagulant or low molecular weight heparin (LMWH). Patients receiving warfarin must be switched to low molecular weight heparin and have achieved stable coagulation profile prior to first dose of protocol therapy. For heparin and LMWH there should be no active bleeding (that is, no bleeding within 14 days prior to first dose of protocol therapy) or pathological condition present that carries a high risk of bleeding (for example, tumor involving major vessels or known varices).
• Subjects must be willing to undergo a CT-guided biopsy (i.e., image-guided percutaneous lung biopsy) to obtain tumor tissue within 28 days before initiation of treatment and after 4 cycles (8 weeks) of treatment.
• Women of childbearing potential (WOCP) must be willing to use birth control as outlined in the protocol.

You may not qualify if:

• Any Grade 3-4 GI bleeding within 3 months prior to study registration.
• History of deep vein thrombosis, pulmonary embolism, or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 3 months prior to study registration.
• Any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to study registration.
• Cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis (any degree) with a history of hepatic encephalopathy, or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis.
• Uncontrolled or poorly-controlled hypertension (\>160 mmHg systolic or \> 100 mmHg diastolic for \>4 weeks) despite standard medical management.
• Prior history of GI perforation/fistula (within 6 months of study registration) or risk factors for perforation.
• Serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to study registration.
• Active brain metastases or carcinomatous meningitis. Subjects with neurological symptoms must undergo a head CT scan or brain MRI to exclude brain metastasis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study drugs and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to study registration. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• Major surgery within 28 days prior to study registration
• Subcutaneous venous access device placement within 7 days prior to study registration.
• Elective or planned major surgery to be performed during the course of the clinical trial.
• Is receiving chronic antiplatelet therapy, including aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen, naproxen, and others), dipyridamole or clopidogrel, or similar agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted.
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). NOTE: HIV testing is not required.
• Known history of testing positive for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody), indicating acute or chronic infection. NOTE: Hepatitis B and Hepatitis C testing is not required.
• Condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.

Sponsors & Collaborators

• Arkadiusz Z. Dudek, MD: lead
• HealthPartners Institute Regions Cancer Care Center: collaborator
• Eli Lilly and Company: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Karmanos Cancer Center (Wayne State University)

Detroit, Michigan, 48201, United States

Location

HealthPartners Institute Regions Cancer Care Center

Minneapolis, Minnesota, 55440, United States

Location

Related Publications (1)

• Dudek AZ, Xi MX, Scilla KA, Mamdani H, Creelan BC, Saltos A, Tanvetyanon T, Chiappori A. Phase 2 Trial of Nivolumab and Ramucirumab for Relapsed Mesothelioma: HCRN-LUN15-299. JTO Clin Res Rep. 2023 Oct 12;4(12):100584. doi: 10.1016/j.jtocrr.2023.100584. eCollection 2023 Dec.

  PMID: 38046376 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Nivolumab; Ramucirumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Fauzia Sharmin
• Organization: Hoosier Cancer Research Network

fsharmin@hoosiercancer.org

(317) 921-2050

Study Officials

• Arkadiusz Z Dudek, MD

  HealthPartners Institute Regions Cancer Care Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 19, 2018
• Study Start: June 26, 2018
• Primary Completion: May 11, 2022
• Study Completion: November 9, 2023
• Last Updated: May 14, 2024
• Results First Posted: October 26, 2023

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)