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A Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

NCT04477343

Description:

The main purpose of this research study is to determine the maximum tolerable dose (MTD) of SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment without evidence of disease progression.

Related Conditions:
  • Pancreatic Ductal Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma
  • Official Title: An Open-label Phase 1 Study to Evaluate the Safety and Tolerability of SX-682 in Combination With Nivolumab as a Maintenance Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

Clinical Trial IDs

  • ORG STUDY ID: UGIP20027
  • NCT ID: NCT04477343

Conditions

  • Pancreatic Ductal Adenocarcinoma
  • Pancreatic Cancer

Interventions

DrugSynonymsArms
SX-682Experimental: SX-682 and Nivolumab
Nivolumab Injectable ProductExperimental: SX-682 and Nivolumab

Purpose

The main purpose of this research study is to determine the maximum tolerable dose (MTD) of SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment without evidence of disease progression.

Detailed Description

      In this study the investigator would like to better understand the maximum tolerable dose
      (MTD) of SX-682 in combination with nivolumab in patients with metastatic pancreatic ductal
      adenocarcinoma who have completed at least 16 weeks of first line chemotherapy treatment
      without evidence of disease progression. In addition, the investigator would like to measure
      the SX-682 pharmacokinetic data in humans. The investigator would also like to assess the
      immunophenotypic and stromal changes to the tumor microenvironment after treatment.
    

Trial Arms

NameTypeDescriptionInterventions
Experimental: SX-682 and NivolumabExperimentalSX-682 Dose: 25, 50, 100, 200, 400mg BID taken as an oral pill Nivolumab Dose: 240mg, every 2 weeks via intravenous infusion
  • SX-682
  • Nivolumab Injectable Product

Eligibility Criteria

        Inclusion Criteria:

        Written Informed Consent and HIPAA Authorization

          1. Subjects must have the nature of the study explained to them

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

          3. Subjects (or an acceptable proxy) must provide a signed and dated IRB/IEC approved
             written informed consent form (ICF) in accordance with regulatory and institutional
             guidelines for both the study and exploratory biomarker analysis obtained via paired
             biopsies.

          4. Subjects (or an acceptable proxy) must provide a signed and dated Health Insurance
             Portability and Accountability Act (HIPAA) authorization.

          5. The ICF and HIPAA authorization must be obtained before conduction and procedures that
             do not form a part of the subject's normal care.

          6. After signing the ICF and HIPAA Authorization, subjects will be evaluated for study
             eligibility during the Screening Period (no more than 28 days before study drug
             administration) according to the following further inclusion/exclusion criteria:

        Study Population/Inclusion Criteria

          1. Male or female subjects, aged at least 18 years

          2. Have histologically or cytologically confirmed metastatic pancreatic ductal
             adenocarcinoma

          3. Completion of at least 16 weeks of first line chemotherapy without evidence of disease
             progression

          4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

          5. Must have measurable disease with at least 1 unidimensional measurable lesion per
             iRECIST

          6. Screening laboratory values within 14 days prior to first dose of study drug:

             WBC ≥ 3000/µL Neutrophils ≥ 1500/µL Platelets ≥ 100,000>µL Hemoglobin ≥ 9.0 g/dL in
             the absence of blood transfusion Creatinine ≤ 1.5 mg/dL AST/ALT ≤ 2.5 x ULN for
             subjects with no liver metastases

               -  5 x ULN for subjects with liver metastases Bilirubin ≤ 1.5 mg/dL sa≤ 3.0 mg/dL
                  for subjects with Gilbert's disease INR or PT ≤ 1.5 x ULN unless receiving
                  anticoagulation therapy aPTT or PTT ≤ 1.5 x ULN unless receiving anticoagulation
                  therapy

          7. Life expectancy of ≥ 12 weeks as judged by the treating physician.

          8. Patient must consent for baseline and on treatment biopsies

          9. Patients must have baseline pulse oximetry ≥ 90% on room air

        Exclusion Criteria:

        Target Disease Exceptions:

        Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are
        eligible if these have been treated and there is no magnetic resonance imaging (MRI- except
        where contraindicated, in which case a CT scan is acceptable) evidence of progression for
        at least 8 weeks after treatment is complete and within 28 days prior to first dose of
        study drug administration. An MRI is not required to rule out brain metastases or
        leptomeningeal metastases. There must also be no requirement for high doses of systemic
        corticosteroids that could result in immunosuppression (>10 mg/day prednisone equivalents)
        for at least 2 weeks prior to study dry administration.

        Medical History and Concurrent Disease

        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. Specifically:

          1. Subjects with active, non-infectious pneumonitis.

          2. Subjects with interstitial lung disease or a history of pneumonitis that required oral
             or intravenous glucocorticoids to assist with management.

          3. Subjects with clinically significant heart disease that affects normal activities.

          4. Clinically significant cardiovascular/ cerebrovascular disease defined as cerebral
             vascular accident, stroke, carotid artery disease transient ischemic attach (< 6
             months prior to enrollment), myocardial infarction (<6 months prior to enrollment),
             unstable angina, congestive heart failure (New York Heart Association Classification
             Class >II) or serious cardiac arrhythmia.

          5. Prior malignancy active within the previous 3 years except for locally curable cancers
             that have been apparently cured, such as basal or squamous cell skin cancer,
             superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.

          6. Subjects with active, known or suspected autoimmune disease. Subjects with 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 are permitted
             to enroll.

          7. Subjects with a condition (including organ or bone marrow transplant) requiring
             systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents)
             or other immunosuppressive medications. Inhaled or topical steroids, and adrenal
             replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
             active autoimmune disease.

          8. Use of other investigational drugs (drugs not marketed for any indication) or
             medications at immunosuppressive doses within 28 days before study drug
             administration.

          9. Patients who received immunotherapy or investigational drug within 4 weeks prior to
             enrollment.

         10. Patients who underwent major surgery within 4 weeks of enrollment (not including
             diagnostic laparoscopy)

         11. History of myelodysplastic syndromes or myeloproliferative neoplasms.

         12. History of or medication induced prolonged QT interval.

         13. Any botanical preparation (e.g., herbal supplements or traditional Chinese medicines)
             intended to treat the disease under study or provide supportive care. Use of marijuana
             and its derivatives for treatment of symptoms related to cancer treatment, even if
             obtained by medical prescription or if its use (even without a medical prescription)
             has been legalized locally.

        Physical and Laboratory Test Findings

          1. A history of Hepatitis B or C, either acute or chronic, as indicated by HBV surface
             antigen positivity, HBV core antibody positivity, or positive HCV antibody with reflex
             to positive HCV RNA.

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

          3. Active tuberculosis (history of exposure or history of positive tuberculosis test plus
             presence of clinical symptoms, physical or radiographic findings).

          4. EKG demonstrating a QTc interval >470 msec or patients with congenital long QT
             syndrome.

        Allergies and Adverse Drug Reaction

          1. History of allergy to study drug components (examples: hydroxpropylmethylcellulose
             phthalate (hypromellose phthalate or HPMCP), microcrystalline cellulose, sodium
             croscarmellose, sodium lauryl sulfate, and silicon dioxide).

          2. History of severe hypersensitivity reaction to any monoclonal antibody (Grade ≥ 3
             NCI-CTCAE v5).

          3. History of anaphylaxis, or recent (within 5 months) history of uncontrolled asthma.

        Sex and Reproductive Status/Special Populations

          1. Women of childbearing potential (WOCBP) must use method(s) of contraception with a
             failure rate of less than 1% while on study and for 5 months after the last dose of
             SX-682 or nivolumab. A WOCBP is defined as any female who has experienced menarche and
             who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy)
             or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea
             in a woman over age 45 in the absence of other biological or physiological causes.

          2. Women under the age of 62 with a history of being postmenopausal must have a
             documented serum follicle stimulating hormone, (FSH) level > 40 mIU/mL.

          3. Women must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L
             or equivalent units of HCG) within 24 hours prior to the start of study drug.

          4. Women must not be breastfeeding.

          5. Men who are sexually active with WOCBP must use any contraceptive method with a
             failure rate of less than 1% per year while on study and for a period at least 7
             months after the last dose of study drug.

          6. Women who are not of childbearing potential and azoospermic men do not require
             contraception.

          7. Individuals who are incarcerated, compulsory detained or otherwise considered a
             vulnerable population
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerable dose [Safety and Tolerability]
Time Frame:through study completion, an average of 6 months
Safety Issue:
Description:Maximum tolerable dose is defined by less than or equal to 30% dose limiting toxicity (DLT) event rate within a given dose combination,

Secondary Outcome Measures

Measure:Progression Free Survival
Time Frame:From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Safety Issue:
Description:Measure of time from study enrollment until progression.
Measure:Overall Survival
Time Frame:From date of enrollment until date of death from any cause up to 24 months
Safety Issue:
Description:Measure of time from study enrollment until death from any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Rochester

Trial Keywords

  • Pancreatic Ductal Adenocarcinoma
  • Pancreatic Cancer

Last Updated

November 5, 2020