Clinical Trials /

A Study of NKTR-214 in Combination With Nivolumab in Patients With Metastatic and/or Locally Advanced Sarcoma

NCT03282344

Description:

The purpose of this study is to test any good and bad effects of the combination of study drugs called NKTR-214 and nivolumab.

Related Conditions:
  • Alveolar Soft Part Sarcoma
  • Chondrosarcoma
  • Dedifferentiated Liposarcoma
  • Leiomyosarcoma
  • Myxofibrosarcoma
  • Osteosarcoma
  • Pleomorphic Liposarcoma
  • Sarcoma
  • Undifferentiated Pleomorphic Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of NKTR-214 in Combination With Nivolumab in Patients With Metastatic and/or Locally Advanced Sarcoma
  • Official Title: A Pilot Study of NKTR-214 and Nivolumab in Selected Patients With Locally Advanced/Metastatic Sarcoma (CA209-9EM)

Clinical Trial IDs

  • ORG STUDY ID: 17-366
  • NCT ID: NCT03282344

Conditions

  • SARCOMA

Interventions

DrugSynonymsArms
NKTR-214participants ≥18 years old NKTR-214 and Nivolumab
Nivolumabparticipants ≥18 years old NKTR-214 and Nivolumab

Purpose

The purpose of this study is to test any good and bad effects of the combination of study drugs called NKTR-214 and nivolumab.

Trial Arms

NameTypeDescriptionInterventions
participants ≥18 years old NKTR-214 and NivolumabExperimentalNKTR-214 0.006mg/kg will be an intravenous (IV) infusion administered over 30 (±5) minutes every 3 weeks. Nivolumab (anti-PD-1) 360mg will be administered every 3 weeks as an IV infusion over 30 (±5) minutes for participants ≥18 years.
  • NKTR-214
  • Nivolumab
participants 12 - 17 years old NKTR-214 0.006mg/kg and NivoExperimentalNKTR-214 0.006mg/kg will be an intravenous (IV) infusion administered over 30 (±5) minutes every 3 weeks. Nivolumab (anti-PD-1) 4.5 mg/kg up to 360 mg will be administered every 3 weeks as an IV infusion over 30 (±5) minutes for participants 12 - 17 years.
  • NKTR-214
  • Nivolumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male or female age ≥ 12 years at the time of informed consent

          -  Be capable, willing, and able to provide written informed consent/assent. For patients
             < 18 years of age, their parents or legal guardians must sign a written informed
             consent. Assent, when appropriate, will be obtained according to institutional
             guidelines.

          -  Be willing to comply with clinical trial instructions and requirements.

          -  Patients ≥ 18 years must be willing to comply with the mandatory biopsies.

          -  Patients must have a histologically confirmed metastatic and/or locally advanced
             sarcoma by the enrolling institution.

          -  For histological specific cohorts, patients must have confirmed metastatic and/or
             locally advanced osteosarcoma, chondrosarcoma, undifferentiated pleomorphic
             sarcoma/malignant fibrous histiocytoma high grade myxofibrosarcoma, vascular sarcoma,
             alveolar soft part sarcoma (ASPS), dedifferentiated/pleomorphic liposarcoma, Small
             Blue Round CellSynovial, or leiomyosarcoma (LMS) by the enrolling institution.

          -  Adequate performance status:

               -  Participants ≥16 years ECOG 0 or 1/KPS 100-70%

               -  Participants <12-15 years Lanksky 100-70%

          -  Patients must have at least one prior line of systemic therapy (e.g.chemotherapy,
             immunotherapy, targeted or biological therapy) for their sarcoma if standard treatment
             is appropriate. Treatment naïve patients may be enrolled if they have refused standard
             systemic treatment. Prior adjuvant therapy will not count provided it was completed
             more than 6 months previously.

          -  Presence of measureable disease per RECIST v1.1.Target lesions must not be chosen from
             a previously irradiated field unless there has been radiographically and/or
             pathologically documented tumor progression in that lesion prior to enrollment.

          -  On echocardiogram, documented left ventricular ejection fraction >45%. Patients may
             instead have a multigated acquisition (MUGA) scan instead of transthoracic
             echocardiogram (TTE).

          -  Adequate organ function

          -  Women of childbearing potential (WOCBP) † must have a negative urine or serum
             pregnancy test at screening and ≤ 72 hours prior to day 1 of study treatment. If the
             urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy
             test will be required.

             † A woman of childbearing potential is a sexually mature female who: has not undergone
             a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for
             at least 24 consecutive months (i.e. has had menses at any time in the preceding 24
             consecutive months).

          -  Male patients with WOCBP partners and female patients of childbearing potential must
             be willing to use an adequate method of contraception as outlined in Section 11.9, for
             the course of the study through 7 months (male participants) or 5 months (female
             participants) after the last dose of study medication.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the patient.

          -  Hematological

               -  Absolute neutrophil count (ANC) ≥1,500 /mcL

               -  Platelets ≥100,000 / mcL

               -  Hemoglobin ≥9 g/dL or ≥5.6 mmol/L

          -  Renal

               -  Serum creatinine OR Measured or calculateda creatinine clearance ≤1.5 X upper
                  limit of normal (ULN) OR ≥60 mL/min for patient with creatinine levels > 1.5 X
                  institutional ULN (GFR can also be used in place of creatinine or CrCl) Hepatic

               -  Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for patients with
                  total bilirubin levels > 1.5 ULN

               -  AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for patients with liver
                  metastases

               -  Albumin ≥ 2.5 mg/dL Coagulation

               -  International Normalized Ratio [34] or Prothrombin Time [35]≤1.5 X ULN unless
                  patient is receiving anticoagulant therapy as long as PT or PTT is within
                  therapeutic range of intended use of anticoagulants

               -  Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless patient is
                  receiving anticoagulant therapy as long as PT or PTT is within therapeutic range
                  of intended use of anticoagulants aCreatinine clearance should be calculated per
                  institutional standard.

        Exclusion Criteria:

          -  History of unstable or deteriorating cardiac disease within the previous 6 months
             prior to screening including but not limited to the following:

               -  Unstable angina or myocardial infarction.

               -  Congestive heart failure (New York Heart Association [NYHA] Class III or IV).

               -  Uncontrolled clinically significant arrhythmias.

          -  Evidence of clinically significant interstitial lung disease or has known history of,
             or any evidence of active, non-infectious pneumonitis. .

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Patients with previously treated brain metastases may participate
             provided:

               -  No current brain metastasis lesion greated than 2 cm. Patients with prior
                  metastasis lesions greater than 2 cm that have been removed by surgical and/or
                  radiotherapy may be enrolled if the lesion has been stable since surgery or
                  radiotherapy.

               -  No new or progressing brain metastatis of any size

               -  No stereotactic radiation or craniotomy within 4 weeks of Cycle 1 Day 1

               -  They are stable (without evidence of progression by imaging for at least four
                  weeks prior to the first dose of trial treatment

               -  No clinically signifigant symptoms secondary to brain metastases(This exception
                  does not include carcinomatous meningitis which is excluded regardless of
                  clinical stability.)

          -  Evidence of clinically significant immunosuppression such as the following:

               -  Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease

               -  Concurrent opportunistic infection

               -  Receiving systemic immunosuppressive therapy (> 2 weeks) including oral steroid
                  doses > 10 mg/day of prednisone or equivalent within 2 months prior to
                  enrollment. (Steroids for pre-medication for imaging studies are allowed.)

          -  History or evidence of symptomatic autoimmune disease (e.g., pneumonitis,
             glomerulonephritis, vasculitis, or other), or history of active autoimmune disease
             that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive
             drugs or biological agents used for treatment of autoimmune diseases) in past 2 years
             prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin
             for diabetes or physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic treatment for autoimmune
             disease.

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) disease

          -  Patients known to be positive for active Hepatitis B (HBsAg reactive), or Hepatitis C
             (HCV RNA (qualitative) is detected)

          -  Prolonged QTcF > 450 ms for men and > 470 ms for women at Screening.

          -  Patients who have received a live vaccine within 30 days of the start date of the
             planned study therapy. Note: Seasonal influenza vaccines for injection are generally
             inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g.,
             Flu-Mist®) are live attenuated vaccines, and are not allowed.

          -  Has a known history of active TB (Bacillus Tuberculosis)

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

          -  Has a known history of active TB (Bacillus Tuberculosis)

          -  Is currently participating and receiving study therapy or using an investigational
             device or has participated in a study of an investigational agent and received study
             therapy or used an investigational device within 4 weeks of the first dose of
             treatment.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent.

               -  Note: Patients with ≤ Grade 2 neuropathy are an exception to this criterion and
                  may qualify for the study.

               -  Note: If patient received major surgery, they must have recovered adequately from
                  the toxicity and/or complications from the intervention prior to starting
                  therapies.

          -  Hypersensitivity to nivolumab or any of its excipients.

          -  Hypersensitivity to NKTR-214 or any of its excipients.

          -  Need for > 2 antihypertensive medications for management of hypertension (including
             diuretics).

          -  Women who are pregnant or breast feeding
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:number of patients with a response
Time Frame:2 years
Safety Issue:
Description:Primary Response Criteria (RECIST 1.1) Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease [1]: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters whi le on study.

Details

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

Trial Keywords

  • NKTR-214
  • NIVOLUMAB
  • 17-366

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