Clinical Trials /

Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)

NCT02553642

Description:

The purpose of this study is to investigate the characteristics of tumors in patients treated with nivolumab and to identify features that help to predict a good or bad response to this drug.

Related Conditions:
  • Melanoma
  • Urothelial Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)
  • Official Title: A Prospectively Designed Study to Assess the Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)

Clinical Trial IDs

  • ORG STUDY ID: 15-126
  • NCT ID: NCT02553642

Conditions

  • Bladder Cancer
  • Melanoma

Interventions

DrugSynonymsArms
Nivolumabmelanoma and bladder cancer patients
Nivolumab plus Ipilimumabmelanoma and bladder cancer patients

Purpose

The purpose of this study is to investigate the characteristics of tumors in patients treated with nivolumab and to identify features that help to predict a good or bad response to this drug.

Trial Arms

NameTypeDescriptionInterventions
melanoma and bladder cancer patientsExperimentalMelanoma pts, treatment will be ipilimumab (3 mg/kg) in combination with nivolumab (1 mg/kg) adm every 3 weeks for 4 doses followed by nivolumab (240 mg) adm every 2 weeks. Treatment may continue for up to 2 years. Bladder ca pts, treatment will be nivolumab (240 mg) adm every 2 weeks. Treatment may continue for up to 2 years. Pts who have disease progression after their 6 week scan may continue to receive nivolumab monotherapy, at discretion of their treating phys & the study PI, until a second scan demonstrates confirmed disease progression. Pts who have disease progression at 6 weeks that is confirmed to be progression on a second scan may be eligible to subsequently receive ipilimumab (3 mg/kg) in combination with nivolumab (1 mg/kg) adm every 3 weeks for 4 doses followed by nivolumab (240mg) adm every 2 weeks. The crossover treatment may begin approx 12 or more weeks after initial treatment on study. Treatment may continue for up to 2 years from the initial dose of nivolumab.
  • Nivolumab
  • Nivolumab plus Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          1. Subjects must have signed and dated an IRB approved written informed consent in
             accordance with regulatory and institutional guidelines. This must be obtained before
             the performance of any protocol related procedures that are not part of normal
             subject care.

          2. Subjects must be willing and able to comply with scheduled visits, treatment
             schedule, laboratory tests, tumor biopsies, and other requirements of the study.

          3. Pathologically confirmed locally advanced or metastatic disease per the treating
             institution's standard of care of the following tumor types

             Subjects with histologically confirmed locally advanced/unresectable or metastatic
             melanoma who meet all of the following criteria:

             i. Subjects have received any number of prior lines of therapy or may be treatment
             naïve ii. If the subject has been treated with a prior line of therapy, they must
             have had disease progression or be refractory to treatment

             OR

             b. Subjects with histologically or cytologically confirmed locally
             advanced/unresectable or metastatic urothelial carcinoma (including mixed histologies
             of urothelial carcinoma with elements of other subtypes) of the renal pelvis, ureter,
             bladder or urethra (referred to broadly in this protocol as "bladder cancer") who
             meet the following criteria: i. Subjects must have disease progression or refractory
             disease after their prior line of therapy. Subjects must have had at least 1 platinum
             based chemotherapy regimen for the treatment of metastatic or locally advanced
             unresectable disease. Subjects may have received any number of prior lines of therapy
             OR

             ii. Subjects with disease recurrence within 1 year of a platinum based neoadjuvant or
             adjuvant therapy for bladder cancer.

             OR

             iii. The subject actively refuses chemotherapy for the treatment of metastatic or
             locally advanced disease considered as standard treatment for this disease stage
             (i.e. a patient who has relapsed >1 year after treatment with neoadjuvant or adjuvant
             chemotherapy), despite being informed by the investigator about the treatment
             options. The subject's refusal must be documented.

          4. Subjects must have measurable disease by CT scans or MRI per RECIST 1.1 criteria.
             Radiographic tumor assessment must be performed within 28 days prior to first dose of
             study drug.

          5. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          6. Age ≥ 18 years.

          7. Subjects must consent to allow for the acquisition of tumor sample prior to starting
             treatment on study (in most cases patients will require a tumor biopsy). This biopsy
             site may be the only site of measurable disease if the site is > 2 cm. The biopsy
             site must, in the opinion of the investigator, be likely to yield acceptable tumor
             sample for core biopsies as described in Appendix 4. It is also acceptable if tumor
             sample is obtained by excision biopsy or during surgery (i.e. if procedure was
             previously planned), provided the tumor sample can be processed as described in
             Appendix 4. In the case that a patient had a tumor sample acquired prior to
             consenting to the study and this tumor sample is acceptable for processing as
             described in Appendix 4 (i.e. frozen sample stored) and the tumor sample was acquired
             within 60 days of starting treatment, this is acceptable and a new biopsy will not be
             required.

          8. Willingness to adhere to the study visit schedule and prohibitions as specified in
             this protocol.

          9. Expected survival of at least 4 months.

         10. At the time of day 1 of the study, patients must have completed chemotherapy,
             targeted therapy, investigational therapy, other immunotherapy, radiation therapy or
             major surgery (requiring general anesthesia) at least 28 days before administration
             of the first dose of nivolumab. Patients undergoing minor surgical procedures and
             biopsies that do not require general anesthesia may begin receiving study therapy if
             sufficiently recovered as determined by the treating investigator. Patients may have
             received prior focal radiotherapy for palliation of an isolated site of disease,
             which must be completed at least 14 days prior to day 1 of the study.

             Palliative (limited-field) radiation therapy is permitted during treatment with study
             drug (s), if all of the following criteria are met:

               1. The lesion being considered for palliative radiation is not a target lesion

               2. Radiation treatment is administered 12 weeks or greater after their first dose
                  of study drug.

         11. All baseline laboratory requirements will be assessed and should be obtained within
             14 days of the first dose of study drug. Screening laboratory values must meet the
             following criteria:

        White blood cells (WBCs) ≥ 2000/μL

        Neutrophils ≥ 1000/μL

        Platelets ≥ 100 x 103/μL

        Hemoglobin ≥ 9.0 g/dL

        Serum creatinine ≤ 1.5 x ULN (or glomerular filtration rate ≥ 40mL/min)

        Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert's syndrome who must have total
        bilirubin ≤ 3.0mg/dL)

        AST and ALT ≤ 3 x ULN

        Albumin ≥ 3.0 g/dL

        Exclusion Criteria:

          1. Active brain metastases or leptomeningeal metastases. Subjects with treated brain
             metastases are eligible if they meet all of the following criteria:

               1. Must be at least 28 days since craniotomy and resection, stereotactic
                  radiosurgery, or whole brain radiotherapy.

               2. Must have no evidence of progression for at least 4 weeks after treatment is
                  complete and within 28 days prior to first dose of study drug administration.

               3. Must have no requirement for immunosuppressive doses of systemic corticosteroids
                  (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug
                  administration.

          2. Any serious or uncontrolled medical disorder that, in the opinion of the
             investigator, may increase the risk associated with study participation or study drug
             administration, impair the ability of the subject to receive protocol therapy or
             interfere with the interpretation of study results.

          3. Other prior malignancy active within the previous 2 years except for local or organ
             confined early stage cancer that has been definitively treated with curative intent
             or does not require treatment, does not require ongoing treatment, has no evidence of
             active disease and has a negligible risk of recurrence and is therefore unlikely to
             interfere with the endpoints of the study.

          4. Subjects with active autoimmune disease, symptoms or conditions. Subjects with
             vitiligo, type I diabetes, residual hypothyroidism due to autoimmune thyroiditis only
             requiring hormone replacement, asymptomatic laboratory evidence of autoimmune disease
             (e.g.: +ANA, +RF, antithyroglobulin antibodies), or conditions not expected to recur
             in the absence of an external trigger are permitted to enroll.

          5. Subjects with a condition requiring systemic treatment with either corticosteroids (>
             10 mg daily prednisone equivalent) or other immunosuppressive medications within 14
             days of first dose of study drug. Inhaled or topical steroids, and adrenal
             replacement steroid doses are permitted in the absence of active autoimmune disease.

          6. Subjects who have received prior therapy with any T cell co-stimulation or checkpoint
             pathways such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, anti-CD137; or other
             medicines specifically targeting T cells are prohibited. Prior therapy with BCG is
             permitted. Prior IL-2 is permitted.

          7. All toxicities attributed to prior anti-cancer therapy other than alopecia and
             fatigue must have resolved to grade 1 (CTCAE version 4) or baseline before
             administration of study drug. Subjects with toxicities attributed to prior
             anti-cancer therapy and which are not expected to resolve and result in long lasting
             sequelae such as neuropathy after platinum-based therapy, are permitted to enroll.

          8. Positive test for hepatitis B virus (HBV) using HBV surface antigen (HBV sAg) test or
             positive test for hepatitis C virus (HCV) using HCV ribonucleic acid (RNA) or HCV
             antibody test indicating acute or chronic infection.

          9. Known history of testing positive for human immunodeficiency virus (HIV) or known
             acquired immunodeficiency syndrome (AIDS).

         10. History of allergy to study drug component or history of severe hypersensitivity
             reaction to any monoclonal antibody

         11. Women who are breast feeding or pregnant as evidenced by positive serum pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) done within 14 days of
             first dosing and urine test within 72 hours of first dosing.

         12. Women of childbearing potential *(WOCBP) not using a medically acceptable means of
             contraception throughout the study treatment and for at least 23 weeks following the
             last dose of study treatment (5 half-lives of study drug plus 30 days duration of
             ovulatory cycle).

             *WOCBP are defined as those who has experienced menarche and who has not undergone
             successful surgical sterilization (hysterectomy, bilateral tubal ligation, or
             bilateral oophorectomy) or is not postmenopausal. Post-menopausal is defined as:
             Amenorrhea ≥ 12 consecutive months without another cause, or For women with irregular
             menstrual periods and on hormone replacement therapy (HRT), a documented serum
             follicle stimulating hormone (FSH) level > 35 mIU/mL

         13. Male subjects who are unwilling to use contraception during the treatment and for at
             least 31 weeks after the last dose of study treatment (5 half-lives of study drug
             plus 90 days duration of sperm turnover).

         14. Subjects who are compulsorily detained for treatment of either a psychiatric or
             physical (e.g., infectious disease) illness.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:response rate
Time Frame:12 weeks
Safety Issue:
Description:The primary clinical endpoint is response rate defined as the proportion of patients who achieve a complete or partial response based on RECIST criteria within 12 weeks of initiating treatment.

Secondary Outcome Measures

Measure:PD-L1 expression
Time Frame:2 years
Safety Issue:
Description:will be evaluated in pre-treatment and on-treatment biopsies. PD-L1 expression on tumor cells will be graded as positive or negative, according to the most up to date standards for the assay in use. PD-L1 expression on immune cells will be graded as \ positive or negative, according to the most up to date standards for the assay in use (At present, <5% staining is called negative whereas 5% or greater is considered positive).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Tumor Mutation
  • Nivolumab
  • Nivolumab plus Ipilimumab
  • Predicted Neo-antigen Burden
  • 15-126

Last Updated

February 28, 2017