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Trial record 1 of 3 for:    Dudek | Mesothelioma
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Phase II Nivolumab and Ramucirumab for Patients With Previously-Treated Mesothelioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03502746
Recruitment Status : Recruiting
First Posted : April 19, 2018
Last Update Posted : August 16, 2019
Sponsor:
Collaborators:
HealthPartners Institute Regions Cancer Care Center
Eli Lilly and Company
Bristol-Myers Squibb
Information provided by (Responsible Party):
Arkadiusz Z. Dudek, MD, Hoosier Cancer Research Network

Tracking Information
First Submitted Date  ICMJE April 11, 2018
First Posted Date  ICMJE April 19, 2018
Last Update Posted Date August 16, 2019
Actual Study Start Date  ICMJE June 26, 2018
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2018)
Response Rate [ Time Frame: 24 months ]
• Evaluate response rate [complete response (CR) + partial response (PR)] of nivolumab in combination with ramucirumab in subjects with previously-treated mesothelioma. Response assessment will be performed using modified RECIST 1.1 criteria.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03502746 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2018)
  • Adverse event assessment [ Time Frame: 24 months ]
    Assess adverse effects (AE) of nivolumab in combination with ramucirumab in subjects with previously-treated mesothelioma.
  • Progression-free survival [ Time Frame: 24 weeks ]
    Measure progression-free survival (PFS) defined as time from registration until objective tumor progression or death rate at 24 weeks with the combination of the anti-Programmed Death 1 (PD-1) agent, nivolumab and the anti-vascular endothelial growth factor receptor 2 (VEGFR2) antibody, ramucirumab in subjects with previously-treated mesothelioma.
  • Overall survival [ Time Frame: 24 months ]
    Measure overall survival (OS) defined as time from registration until death from any cause at 2 years after treatment with nivolumab in combination with ramucirumab in subjects with previously-treated mesothelioma.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Nivolumab and Ramucirumab for Patients With Previously-Treated Mesothelioma
Official Title  ICMJE Phase II Study of Nivolumab and Ramucirumab for Patients With Previously-Treated Mesothelioma:Hoosier Cancer Research Network LUN15-299
Brief Summary This study will evaluate the combination of Nivolumab and Ramucirumab in patients with previously-treated mesothelioma.
Detailed Description The programmed death ligand 1 (PD-L1) [16] and VEGFR2 [34] are highly-expressed on mesothelioma cells, and are therefore attractive options for this cancer. We chose to study the combination of ramucirumab with nivolumab because of the potential efficacy of these two agents in mesothelioma and because of the potential synergistic activity between them [30]. As previously discussed, immunotherapies such as anti-PD-1 inhibitors must contend with a hostile, immunosuppressive tumor microenvironment due to angiogenesis that results in hypoxia. This hypoxia decreases the ability of antibodies to infiltrate the tumor. We hypothesize that the normalization of tumor vasculature (by reducing the area of the tumor that is hypoxic) with an anti-VEGF strategy (i.e., ramucirumab) used in synergy with a PD-1 inhibitor will facilitate the infiltration of T-lymphocytes into tumor parenchyma. We will conduct a phase II study based on this premise using nivolumab and ramucirumab as second-line therapy in patients with malignant mesothelioma who have failed standard doublet platinum and anti-folate therapy.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Mesothelioma, Malignant
Intervention  ICMJE
  • Drug: Nivolumab
    Nivolumab 240mg, IV over 30 minutes.
    Other Name: Opdivo
  • Drug: Ramucirumab
    8mg/kg, IV over 60 minutes.
    Other Name: Cyramza
Study Arms  ICMJE Experimental: Nivolumab + Ramucirumab
Nivolumab 240mg IV + Ramucirumab 8mg/kg IV
Interventions:
  • Drug: Nivolumab
  • Drug: Ramucirumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 18, 2018)
35
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2021
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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 ≥ 9 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 two methods of birth control. The two birth control methods can be either two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. WOCP should begin using birth control from the screening visit, throughout the study period, and up to 5 months following the last dose of study drugs.
  • Men who are not surgically or medically sterile must agree to use an acceptable method of contraception. Male subjects with female sexual partners who are pregnant, possibly pregnant, or who could become pregnant during the study must agree to use condoms with spermicide from the date of the first dose of study drug, throughout the study period, and through at least 7 months after the last dose of study drug. Total abstinence for the same study period is an acceptable alternative.
  • Measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to modified RECIST 1.1 criteria, and obtained by imaging within 28 days prior to study registration.
  • Prior intracavity cytotoxic or sclerosing agents (including bleomycin) is acceptable.
  • Radiation therapy must be completed > 28 days before study registration, and the measurable disease must be outside of the radiation port.
  • Pemetrexed-containing chemotherapy must be completed > 28 days before study registration.
  • Must provide written informed consent and HIPAA authorization approved by an Institutional Review Board (IRB). NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  • All previous toxicity resolved to Grade 1 or less.

Exclusion Criteria:

  • 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.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.

    o NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

  • Received a live vaccine within 30 days prior to the first dose of trial treatment. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid (oral) vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines and are not allowed.
  • History of interstitial lung disease or active, non-infectious pneumonitis.
  • Female subject is pregnant or breast-feeding.

    • NOTE: Women of childbearing potential (WOCP) must have a negative pregnancy test (either serum β-HCG with a sensitivity of 50 mIU/ml or urine dipstick within 24 hours of study registration).
    • NOTE: Women are not considered to be of childbearing potential if they meet at least one of the following: 1) surgically sterilized, or 2) postmenopausal (a woman who is ≥45 years of age and has not had menses for greater than 1 year), or 3) not heterosexually active for the duration of the study. See section 5.6.2.
  • Major blood vessel invasion or significant intratumor cavitation.
  • If they experience hemoptysis (defined as bright red blood or ≥ ½ teaspoon) within 2 months prior to first dose of protocol therapy or with radiographic evidence of intratumor cavitation or has radiologically documented evidence of major blood vessel invasion or encasement by cancer.
  • Any condition that, in the opinion of the investigator, might jeopardize the safety of the subject or interfere with protocol compliance.
  • Any mental or medical condition that prevents the subject from giving informed consent or participating in the trial.
  • Any pathological condition that carries a high risk of bleeding (for example, tumor involving major vessels or known varices.)
  • Known hypersensitivity to nivolumab or ramucirumab or any of their components.
  • Known history of active tuberculosis.
  • Received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, localized Gleason ≤ grade 7 prostate cancers. Subjects with other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to enrollment may be eligible for study after discussion with the sponsor-investigator
  • Treatment with any investigational agent within 28 days prior to study registration. The subject must have recovered from the acute toxic effects of the regimen.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Arkadiusz Z Dudek, MD 651-254-3321 Arkadiusz.Z.Dudek@HealthPartners.Com
Contact: Dylan Cregar 3176345842 ext 38 dcregar@hoosiercancer.org
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03502746
Other Study ID Numbers  ICMJE HCRN-LUN15-299
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Arkadiusz Z. Dudek, MD, Hoosier Cancer Research Network
Study Sponsor  ICMJE Arkadiusz Z. Dudek, MD
Collaborators  ICMJE
  • HealthPartners Institute Regions Cancer Care Center
  • Eli Lilly and Company
  • Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Arkadiusz Z Dudek, MD HealthPartners Institute Regions Cancer Care Center
PRS Account Hoosier Cancer Research Network
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP