Clinical Trials /

Adjuvant Treatment Determined By Pathological Response To Neoadjvuant Nivolumab

NCT04013854

Description:

Subjects with resectable melanoma will receive neoadjuvant nivolumab followed by surgical resection. Post-operatively, subjects will receive open-label treatment with up to 1 year of adjuvant nivolumab or ipilimumab plus nivolumab as determined by pathologic response at the time of resection.

Related Conditions:
  • Melanoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Adjuvant Treatment Determined By Pathological Response To Neoadjvuant Nivolumab
  • Official Title: Adjuvant Nivolumab or Ipilimumab + Nivolumab Determined By Pathological Response To A Single Dose Of Neoadjvuant Nivolumab

Clinical Trial IDs

  • ORG STUDY ID: UPCC 02619
  • NCT ID: NCT04013854

Conditions

  • Melanoma Stage III
  • Melanoma

Interventions

DrugSynonymsArms
nivolumabArm A: Adjuvant Nivolumab (Complete Pathological Response)
IpilimumabArm C: Adjuvant Combination (Less than Complete Response)

Purpose

Subjects with resectable melanoma will receive neoadjuvant nivolumab followed by surgical resection. Post-operatively, subjects will receive open-label treatment with up to 1 year of adjuvant nivolumab or ipilimumab plus nivolumab as determined by pathologic response at the time of resection.

Detailed Description

      Subjects with Stage III resectable melanoma will receive one dose of nivolumab 480 mg IV,
      then undergo standard definitive surgery approximately 4 weeks after the initial dose of
      nivolumab. Post-operatively, subjects will receive open-label treatment with up to 1 year of
      adjuvant nivolumab 480 mg IV every 4 weeks or ipilimumab plus nivolumab, as determined by
      pathologic response at the time of resection. Subjects with pathologic complete response or
      near pathologic complete response (PathCR/nearCR) (Arm A) receive adjuvant nivolumab for up
      to one year. Subjects with <PathCR/nearCR are randomized 1:2 to either adjuvant nivolumab
      (480 mg) for up to one year (Arm B) or adjuvant ipilimumab (1mg/kg) plus nivolumab (3mg/kg)
      for 4 doses and then nivolumab (480 mg) alone for a total of one year (Arm C).
    

Trial Arms

NameTypeDescriptionInterventions
Arm A: Adjuvant Nivolumab (Complete Pathological Response)Active Comparator480 mg IV for up to one year
  • nivolumab
Arm B: Adjuvant Nivolumab (Less than Complete Response)Active Comparator480 mg IV for up to one year
  • nivolumab
Arm C: Adjuvant Combination (Less than Complete Response)Experimentalipilimumab (1mg/kg) plus nivolumab (3mg/kg) for 4 doses and then nivolumab (480 mg) alone for a total of one year
  • nivolumab
  • Ipilimumab

Eligibility Criteria

        Inclusion Criteria:

          -  The subject must have stage IIIB, IIIC or IIID resectable melanoma that involves at
             least one measurable lesion by RECIST 1.1 criteria. Subjects may not have a diagnosis
             of uveal or mucosal melanoma.

          -  Either the subject or the subject's legally authorized representative must be willing
             and able to provide written informed consent before the performance of any
             protocol-related procedures.

          -  The subject must be ≥18 years of age on day of signing informed consent.

          -  The subject must have a performance status of 0 or 1 on the ECOG Performance Scale.

          -  The subject must demonstrate adequate organ function as defined in Table 1; all
             screening labs must be performed within 28 days of treatment initiation.

               -  Hematologic System: Absolute neutrophil count (ANC) ≥1500/mcL; Platelets
                  ≥100,000/mcL; Hemoglobin ≥9 g/dL or ≥5.6 mmol/L

               -  Renal System: Serum creatinine OR measured or calculateda creatinine clearance
                  (GFR can also be used in place of creatinine or CrCl) ≤1.5 X upper limit of
                  normal (ULN) OR ≥50 mL/min for subject with creatinine levels >1.5 X
                  institutional ULN

               -  Hepatic System: Serum total bilirubin ≤1.5 X ULN OR Direct bilirubin ≤ ULN for
                  subjects with total bilirubin levels >1.5 ULN; AST (SGOT) and ALT (SPGT) ≤2.5 X
                  ULN OR ≤5 X ULN for subjects with liver metastases

          -  A female participant is eligible to participate if she is not pregnant (see Appendix
             3), not breastfeeding, and at least one of the following conditions applies: A.) Not a
             woman of childbearing potential (WOCBP) as defined in Appendix 3 OR B.) A WOCBP who
             agrees to follow the contraceptive guidance in Appendix 3 during the treatment period
             and is willing to use a highly effective method of contraception or abstain from
             heterosexual intercourse for at least 2 weeks prior to the time of first dose of study
             medication through 5 months after the last dose of study medication.

          -  Female subjects of childbearing potential must have a negative urine or serum
             pregnancy test within 72 hours prior to receiving the first dose of study medication.

          -  Male subjects must agree to follow the contraceptive guidance in Appendix 3 starting
             with the first dose of study medication, while on study, through 7 months after the
             last dose of study medication.

        Exclusion Criteria:

          -  Subject has unresectable disease; i.e. in the opinion of the surgical oncologist, all
             of the subject's melanoma cannot be completely removed with a clear margin.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g.,
             CTLA-4, OX 40, CD137), interferon, high dose IL-2 or any other antibody or drug
             specifically targeting T-cell co-stimulation or checkpoint pathways.

          -  Has received prior systemic anti-cancer therapy including investigational agents
             within 4 weeks prior to the first dose of study drug. Note: Participants must have
             recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants
             with ≤Grade 2 neuropathy are an exception to this criterion.

          -  If participant received major surgery, they must have recovered adequately from the
             toxicity and/or complications from the intervention prior to starting study treatment.

          -  Subject has received transfusion of blood products (including platelets or red blood
             cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or
             recombinant erythropoietin) within 4 weeks to the first dose of study drug.

          -  Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

          -  Is currently participating in or has participated in a study of an investigational
             agent or has used an investigational device within 4 weeks prior to the first dose of
             study treatment.

          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
             immunosuppressive therapy within 7 days prior to the first dose of study drug.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of
             the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that
             have undergone potentially curative therapy are not excluded.

          -  Has active autoimmune disease that has required systemic treatment in the past 3
             months (i.e. with use of disease modifying agents, corticosteroids or
             immunosuppressive drugs). 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.

          -  Has evidence of active interstitial lung disease or a history of (non-infectious)
             pneumonitis that required steroids or has current pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Patients known to be positive for Human Immunodeficiency Virus (HIV) if they have a
             CD4 count of less than 350 mm3 and a serum HIV viral load > 25,000 IU/mL

          -  Has active Hepatitis B infection or active Hepatitis C virus infection as determined
             by medical record review.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the study, interfere with the subject's
             participation for the full duration of the study, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the study, starting with the screening visit through 5 months,
             if female, or 7 months, if male, after the last dose of investigational drug.

          -  Prisoners or subjects who are involuntarily incarcerated.

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

Primary Outcome Measures

Measure:Recurrence-Free Survival
Time Frame:1 year
Safety Issue:
Description:Recurrence-free survival (RFS) is defined as the time from date of surgery to date of disease recurrence, death due to any cause or most recent follow-up documenting freedom from recurrence (i.e., scan date).

Secondary Outcome Measures

Measure:Frequency and Incidence of Adverse Events
Time Frame:Up to 13 months
Safety Issue:
Description:Toxicity will be determined by scoring treatment-related AEs and SAEs. CTCAE version 5.0 grades will be employed.
Measure:Pathological Response Rate
Time Frame:Approximately 4 weeks
Safety Issue:
Description:
Measure:Overall Survival
Time Frame:Up to 7 Years
Safety Issue:
Description:Overall survival (OS) is defined as the time from date of surgery to date of death due to any cause or last subject contact alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Abramson Cancer Center of the University of Pennsylvania

Trial Keywords

  • nivolumab
  • ipilimumab
  • adjuvant
  • neoadjuvant
  • surgery

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