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Trial record 61 of 2732 for:    tumor | Neuroendocrine Tumors

Nivolumab With Ipilimumab in Subjects With Neuroendocrine Tumors

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ClinicalTrials.gov Identifier: NCT03420521
Recruitment Status : Recruiting
First Posted : February 2, 2018
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Brief Summary:
This is a single arm open-label design study looking at Nivolumab plus Ipilimumab in patients with Advanced Neuroendocrine Tumors. Patients will be dosed Nivoluma 240mg IV over 60 minutes every 2 weeks and Ipilimumab 1mg/kg IV over 30 minutes every 6 weeks. Once cycle will include 3 doses of Nivolumab and 1 dose of Ipilimumab. The objective of this study is to evaluate the objective response rate of combination nivolumab and ipilimumab in advanced, well-differentiated neuroendocrine tumors. Durability of response, and PFS will also be described.

Condition or disease Intervention/treatment Phase
Neuroendocrine Tumors Carcinoid Tumor Drug: Nivolumab Drug: Ipilimumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Single Arm Phase II Study of Nivolumab in Combination With Ipilimumab in Subjects With Advanced Neuroendocrine Tumors
Actual Study Start Date : March 9, 2018
Estimated Primary Completion Date : January 15, 2023
Estimated Study Completion Date : January 15, 2024


Arm Intervention/treatment
Nivolumab plus Ipilimumab
Nivolumab-240 mg IV over 60 minutes Q2W Ipilimumab 1mg/kg IV over 30 minutes Q6W
Drug: Nivolumab
240mg IV over 60 minutes Q2W

Drug: Ipilimumab
1mg/kg IV over 30 minutes Q6W




Primary Outcome Measures :
  1. Objective Response Rate of neuroendocrine tumor (NET) of the lung [ Time Frame: 6 weeks post-intervention ]
    Proportion of participants with reduction in size of advanced, progressive, well-differentiated nonfunctional neuroendocrine tumor (NET) of the lung treated with nivolumab plus ipilimumab.

  2. Objective Response Rate of neuroendocrine tumor (NET) of the pancreas [ Time Frame: 6 weeks post-intervention ]
    Proportion of participants with reduction in size of advanced, progressive, well-differentiated nonfunctional neuroendocrine tumor (NET) of the pancreas treated with nivolumab plus ipilimumab.

  3. Objective Response Rate of neuroendocrine tumor (NET) of the gastrointestinal (GI) tract [ Time Frame: 6 weeks post-intervention ]
    Proportion of participants with reduction in size of advanced, progressive, well-differentiated nonfunctional neuroendocrine tumor (NET) of the gastrointestinal (GI) tract treated with nivolumab plus ipilimumab.


Secondary Outcome Measures :
  1. Safety as assessed by number of treatment-emergent adverse events [ Time Frame: 2 weeks post-intervention ]
    Number of treatment-emergent adverse events (safety and tolerability) of nivolumab plus ipilimumab by characterization of toxicities in subjects with advanced well-differentiated nonfunctional NET of the lung, pancreas or GI tract.

  2. Safety as assessed by number of treatment dose interruptions [ Time Frame: 2 weeks post-intervention ]
    Quantification of treatment dose interruptions in subjects with advanced well-differentiated nonfunctional NET of the lung, pancreas or GI tract.

  3. Efficacy as assessed by Progression Free Survival (PFS) at 6 months [ Time Frame: 6 months post-intervention ]
    Efficacy via progression free survival (PFS) at 6 months of the combination of nivolumab and ipilimumab in subjects with advanced well-differentiated nonfunctional NET of the lung, pancreas or GI tract

  4. Efficacy as assessed by Progression Free Survival (PFS) at 12 months [ Time Frame: 12 months post-intervention ]
    Efficacy via progression free survival (PFS) at 12 months of the combination of nivolumab and ipilimumab in subjects with advanced well-differentiated nonfunctional NET of the lung, pancreas or GI tract

  5. Efficacy as assessed by Progression Free Survival (PFS) at 24 months [ Time Frame: 24 months post-intervention ]
    Efficacy via progression free survival (PFS) at 24 months of the combination of nivolumab and ipilimumab in subjects with advanced well-differentiated nonfunctional NET of the lung, pancreas or GI tract

  6. Median progression free survival [ Time Frame: up to 2 years post-intervention ]
    Median number months without disease progression

  7. Efficacy as assessed by disease control rate (DCR) [ Time Frame: 2 years post-intervention ]
    Percentage of participants who achieve partial or complete response to combination of nivolumab and ipilimumab.

  8. Efficacy as assessed by Duration of Response (DOR) [ Time Frame: Up to 2 years post-intervention ]
    Number of months from documentation of tumor response to disease progression

  9. Efficacy as assessed by Overall Survival (OS) [ Time Frame: Up to 2 years post-intervention ]
    Number of months participants stay alive after treatment with the combination of nivolumab and ipilimumab in subjects with advanced well-differentiated nonfunctional NET of the lung, pancreas or GI tract



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with histologically confirmed advanced, progressive, well-differentiated nonfunctional NET of the pancreas, lung or gastrointestinal (GI) tract per the 7th International Association for the Study of Lung Cancer classification (IASLC) or the American Joint Committee on Cancer (AJCC) Staging Handbook, 7th edition.

    • Measurable disease by CT or MRI per RECIST 1.1 criteria (Appendix 3); radiographic tumor assessment performed within 28 days before treatment. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site after the completion of radiation therapy.
    • Prior therapy, including everolimus, octreotide, surgery, chemoradiation, is all permitted after being properly noted. This prior therapy must have been completed at least 28 days prior to study enrollment.
    • Previously untreated patients who decline standard therapy for their cancer are allowed to enroll.
    • Subjects are to have tumor tissue sample available at central lab for PD -L1 IHC testing during the screening period. Subjects can initiate therapy before the result of IHC testing. The tumor tissue sample must be a core needle biopsy, excisional or incisional biopsy. It may be fresh or archival if obtained within 6 months prior to enrollment, and there can have been no systemic therapy (e.g., adjuvant or neoadjuvant chemotherapy) given after the sample was obtained.
    • (Stage 2 only) Subjects must be willing to undergo 2 sets of core needle biopsies (pre-treatment and at 6-8 weeks on therapy) if there are lesions amenable to biopsy. Subjects without a lesion amendable to biopsy will still be permitted to enroll provided they have an archival tumor sample for PD-L1 IHC testing. An optional core biopsy will be requested at progression.
    • ECOG performance status ≤ 1 (see Appendix 1)
    • Prior palliative radiotherapy to non-CNS lesions must have been completed at least 2 weeks prior to treatment. Subjects with symptomatic tumor lesions at baseline that may require palliative radiotherapy within 4 weeks of first treatment are strongly encouraged to receive palliative radiotherapy prior to treatment.
    • Patients must have normal organ and marrow function as defined below:
  • - WBC ≥1,500/mcL
  • - absolute neutrophil count ≥1,000/mcL
  • - hemoglobin ≥ 8.0 g/dL
  • - platelets ≥75,000/mcL
  • - total bilirubin ≤ 1.5 x ULN (patients with Gilbert's syndrome may have serum bilirubin ≤ 3 x ULN)
  • - AST/ALT ≤ 3 × institutional ULN (≤ 5 x ULN in the presence of liver metastases)

    - creatinine

  • ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below):
  • Female:
  • CrCl = (140 - age in years) x weight in kg x 0.85

    o 72 x serum creatinine in mg/dL

  • Male:
  • CrCl = (140 - age in years) x weight in kg x 1.00

    - 72 x serum creatinine in mg/dL

    • Age ≥18 years of age
    • Patients must have recovered from adverse events due to prior treatment to ≤ grade 1, except for alopecia and sensory neuropathy ≤ grade 2.
    • Patients must be able to understand and the willingness to sign a written informed consent document.
  • Exclusion Criteria:

    • Subjects with poorly differentiated or small cell carcinoma histology
    • Subjects with disease that is amenable to surgical resection.
    • Subjects with history of or active symptoms of carcinoid syndrome
    • Hepatic intra-arterial embolization or peptide receptor radionuclide therapy (PRRT) within 4-8 weeks; cryoablation, radiofrequency ablation or trans-arterial chemoembolization of hepatic metastases within ≤ 4 weeks of study enrollment
    • Subjects with symptomatic untreated CNS metastases are excluded.
    • Subjects are eligible if CNS metastases are asymptomatic or adequately treated and subjects are neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to first treatment.
    • In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of <10 mg daily prednisone (or equivalent) for at least 2 weeks prior to first treatment.
    • Subjects with carcinomatous meningitis
    • Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before first treatment.
    • Pregnant or breast-feeding women
    • Women of child-bearing potential, who are biologically able to conceive, and not employing two forms of highly effective contraception. Highly effective contraception must be used throughout the trial and up to 8 weeks after the last dose of study drug (e.g. male condom with spermicidal; diaphragm with spermicide; intra-uterine device). Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 14 days prior to starting study drug.
    • Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
    • Other active malignancy requiring concurrent intervention.
    • Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal replacement steroid 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
    • Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
    • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
    • Known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interferes with the interpretation of safety results.
    • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
    • Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
    • History of allergy or hypersensitivity to study drug components

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03420521


Contacts
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Contact: Christine Hann, MD/PhD 410-502-0678 chann1@jhmi.edu
Contact: Rachel Levy 410-502-8738 rlevy16@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Medical Institution Recruiting
Baltimore, Maryland, United States, 21287
Contact: Christine Hann    410-502-0658    chann1@jhmi.edu   
Contact: Rachel Levy    410-502-8738    rlevy16@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Bristol-Myers Squibb
Investigators
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Principal Investigator: Christine Hann, MD/PhD Johns Hopkins University

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03420521     History of Changes
Other Study ID Numbers: J17156
IRB00151698 ( Other Identifier: JHM IRB )
First Posted: February 2, 2018    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
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Neoplasms
Neuroendocrine Tumors
Carcinoid Tumor
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Neoplasms, Glandular and Epithelial
Adenocarcinoma
Carcinoma
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents