Clinical Trials /

Safety and Efficacy Study of Daily SPL-108 Injections In Conjunction With Paclitaxel in Women With Ovarian Cancer

NCT03078400

Description:

Up to 18 women with ovarian cancer will administer up to two injections of SPL-108 daily in combination with weekly doses of Paclitaxel. They will be monitored for safety and efficacy for up to 6 months, until disease progression or unacceptable toxicity.

Related Conditions:
  • Ovarian Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Safety and Efficacy Study of Daily SPL-108 Injections In Conjunction With Paclitaxel in Women With Ovarian Cancer
  • Official Title: An Open-label Phase 1 Trial of the Safety and Efficacy of Daily Subcutaneous SPL-108 Injections When Used In Combination With Paclitaxel In Patients With Platinum-resistant, CD44+, Advanced Ovarian Epithelial Cancer

Clinical Trial IDs

  • ORG STUDY ID: SPL-006
  • NCT ID: NCT03078400

Conditions

  • Ovarian Epithelial Cancer

Interventions

DrugSynonymsArms
SPL-108Safety Phase

Purpose

Up to 18 women with ovarian cancer will administer up to two injections of SPL-108 daily in combination with weekly doses of Paclitaxel. They will be monitored for safety and efficacy for up to 6 months, until disease progression or unacceptable toxicity.

Detailed Description

      This is an open-label 2-arm trial. Eligible subjects will be screened and enrolled
      sequentially into 1 of 2 Arms:

      Arm I: N=6 to 12 subjects, Safety Phase

        -  Cohort 1 SPL-108 x 1 injection daily + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28
           day cycles

        -  Cohort 2 SPL-108 BID + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles

      For Arm I, at least 1 week will elapse between Dose 1 for each subject.

      In Cohort 1, 3 subjects will be enrolled: if 1 dose-limiting toxicity (DLT) occurs, 3
      subjects will be added at this dose level; if 0/3 or 1/6 DLTs occur, Cohort 2 will initiate
      enrolling subjects; if 2 or more DLTs occur at this dose level, subjects will not be enrolled
      in Cohort 2 and the trial will be terminated.

      In Cohort 2, 3 subjects will be enrolled: if 1 DLT occurs, 3 subjects will be added at this
      dose level; if 0/3 or 1/6 DLTs occur, Arm II will initiate enrolling subjects at the SPL-108
      BID dose; if 2 or more DLTs occur, Arm II will initiate enrolling subjects at the SPL-108
      dose one time each day.

      Arm II: N=up to 12, Exploratory Expansion Phase

      • Cohort 3: SPL-108 daily dose (to be determined in Arm I) + 80 mg/m2 PTX weekly on Days 1,
      8, and 15 in 28 day cycles.

      A Safety Committee will meet at the end of each Arm I Cohort as well as periodically to
      review safety data and make recommendations for trial progression. The primary efficacy
      outcome, Response Evaluation Criteria in Solid Tumors Committee (RECIST 1.1) criteria, will
      be assessed on Day 15 of Cycles 2, 4, and 6.
    

Trial Arms

NameTypeDescriptionInterventions
Safety PhaseExperimentalSix to 12 subjects Cohort 1 SPL-108 injection daily + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles Cohort 2 SPL-108 BID injection + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles
  • SPL-108
Exploratory Expansion PhaseExperimentalUp to 12 subjects • Cohort 3: SPL-108 daily dose (to be determined in Arm I) + 80 mg/m2 PTX weekly on Days 1, 8, and 15 in 28 day cycles.
  • SPL-108

Eligibility Criteria

        Inclusion Criteria:

          1. Females ≥18 years of age

          2. Platinum-resistant recurrent or metastatic epithelial ovarian carcinoma

          3. Positivity on CD44 assay as defined by strong (+++) or moderate (++) staining in 20%
             or more of the tumor tissue/stroma as obtained by biopsy or paracentesis

          4. Status post first-line therapy with definitive surgery (which provided tissue for
             pathologic diagnosis) and chemotherapy

          5. Original diagnosis has been confirmed through a histopathologic review of the primary
             tumor slides by an expert pathologist at the Principal Investigator's institution

          6. Disease has progressed or recurred during or less than 6 months after platinum-based
             chemotherapy at some point during the subject's course.

          7. No more than 3 prior regimens of cytotoxic chemotherapy unless approved by the sponsor
             (Note: all platinum-containing regimens are not to be counted separately but are
             considered to be a single regimen for the purposes of this criterion)

          8. Measurable disease by RECIST 1.1 criteria

          9. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, or 2

         10. Women with childbearing potential and partners must both use effective contraception
             during the study and for 3 months after the last dose

         11. Life expectancy of at least 6 months

         12. Able to understand and comply with the study procedures, understand the risks involved
             in the study, and provide written informed consent before the first study-specific
             procedure

        Exclusion Criteria:

          1. Treatment with cytotoxic chemotherapy for malignancies other than ovarian cancer
             within the past 5 years

          2. Fewer than 28 days before Cycle 1 Day 1 since any prior chemotherapy (less than 42
             days in the case of mitomycin or a nitrosourea)

          3. Fewer than 28 days before Cycle 1 Day 1 since administration of hormonal or biological
             anti-neoplastic agents

          4. Concomitant use of other cytotoxic or cytostatic drugs other than PTX

          5. Abnormal clinical laboratory values within 14 days prior to initiation of dosing, as
             indicated by:

               -  Hemoglobin level <9.0 gm/L

               -  Platelet count <100,000/mm3

               -  Granulocyte count <1500/mm3

               -  Serum creatinine level ≥2.5 mg/dL (221 μmol/L)

               -  Liver aminotransferase levels greater than 3 times the laboratory's upper limit
                  of normal (greater than 5 times the laboratory's upper limit of normal if the
                  liver is known to be involved with tumor)

          6. Contraindication to the use of PTX

          7. Pregnancy or breast-feeding at time of Screening and throughout the study.

          8. Active, uncontrolled infection

          9. Participation in another investigational drug trial concurrently or within 30 days of
             Cycle 1 Day 1, or a vaccine trial within 90 days of Cycle 1 Day 1

         10. Significant acute or chronic medical or psychiatric illness that, in the judgment of
             the Investigator, could compromise subject safety, limit the subject's ability to
             complete the trial, and/or compromise the objectives of the trial
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Adverse Events (Safety)
Time Frame:Until dose-limiting toxicity, disease progression or 6 months
Safety Issue:
Description:Includes adverse events, laboratory data, physical examination findings, vital signs, weight and ECOG Performance Status

Secondary Outcome Measures

Measure:Response to Investigational Product
Time Frame:Until dose-limiting toxicity, disease progression or 6 months
Safety Issue:
Description:Objective response (OR) through imaging assessments
Measure:Response to Investigational Product
Time Frame:Until dose-limiting toxicity, disease progression or 6 months
Safety Issue:
Description:Objective response (OR) through changes in CA 125 levels
Measure:Response to Investigational Product
Time Frame:Until dose-limiting toxicity, disease progression or 6 months
Safety Issue:
Description:Objective response (OR) as assessed through changes in Quality of Life (FACT-O Questionnaire)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Splash Pharmaceuticals, Inc.

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