Clinical Trials /

Study of the Safety, Pharmacokinetics and Efficacy of EDO-S101, in Patients With Advanced Solid Tumors

NCT03345485

Description:

Tinostamustine (EDO-S101) is a new chemical entity, an AK-DAC (a first-in-class alkylating deacetylase inhibiting molecule) that, in preclinical studies, has been shown to simultaneously improve access to the DNA strands within cancer cells, break them and block damage repair. This Phase 1/2 study will enroll patients with various advanced solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Gastrointestinal Stromal Tumor
  • Ovarian Carcinoma
  • Small Cell Lung Carcinoma
  • Soft Tissue Sarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety, Pharmacokinetics and Efficacy of EDO-S101, in Patients With Advanced Solid Tumors
  • Official Title: A Phase 1/2 Study to Investigate the Safety, Pharmacokinetics and Efficacy of EDO-S101, a First-in-Class Alkylating Histone Deacetylase Inhibition (HDACi) Fusion Molecule, in Patients With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: EDO-S101-1002
  • NCT ID: NCT03345485

Conditions

  • Small-cell Lung Cancer
  • Soft Tissue Sarcoma
  • Triple-negative Breast Cancer
  • Ovarian Cancer

Interventions

DrugSynonymsArms
Tinostamustine (EDO-S101)Tinostamustine (EDO-S101)

Purpose

Tinostamustine (EDO-S101) is a new chemical entity, an AK-DAC (a first-in-class alkylating deacetylase inhibiting molecule) that, in preclinical studies, has been shown to simultaneously improve access to the DNA strands within cancer cells, break them and block damage repair. This Phase 1/2 study will enroll patients with various advanced solid tumors.

Detailed Description

      The study consists of 2 phases:

        -  Phase 1: Dose Escalation until MAD

        -  Phase 2: Evaluation of Toxicity and Response Rate in Selected Solid Tumor Cohorts

      The study is designed as an open label, Phase 1/2 trial of single agent EDOS101. The Phase 1
      portion of the study is designed to define the MTD for two (2) administration schedules by
      evaluating toxicities during dose escalation until MAD. The Phase 2 portion of the study is
      designed to evaluate ORR and CBR at four (4) or six (6) months depending on the type of solid
      tumor.
    

Trial Arms

NameTypeDescriptionInterventions
Tinostamustine (EDO-S101)ExperimentalPhase 1: Schedule A: Tinostamustine (EDO-S101), IV, 60mg/m2 up to 150mg/m2 Day 1 and 15 of each 28 day cycle Schedule B: Tinostamustine (EDO-S101, IV, 60mg/m2 up to 150mg/m2 Day 1, 8 and 15 of each 28 day cycle Phase 2: The RP2D and selected schedule will be further investigated in patients with specific types of solid tumors: relapsed/refractory SCLC, soft tissue sarcoma, non-Kit GIST, triple negative breast, and ovarian cancers.
  • Tinostamustine (EDO-S101)

Eligibility Criteria

        General Phase 1 and 2 Inclusion Criteria:

          1. Signed informed consent.

          2. Patients age ≥18 years at signing the informed consent.

          3. Histologically confirmed diagnosis of advanced or metastatic solid tumors, disease
             should have progressed following at least one line of therapy and no other standard
             therapy with proven clinical benefit is available

          4. Patients with secondary metastasis to the CNS are eligible if they have met certain
             criteria.

          5. Evaluable disease; either measurable on imaging or with informative tumor marker.

          6. Discontinuation of previous cancer therapies at least three (3) weeks or 5 half-lives,
             whichever is shorter.

          7. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

          8. Neutrophils ≥1,500 μL.

          9. Platelets ≥100,000 μL.

         10. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤ 3 upper limit of
             normal (ULN). In cases with liver involvement ALT/ AST ≤ 5× ULN.

         11. Total bilirubin ≤1.5 mg/dL unless elevated due to known Gilbert's syndrome.

         12. Creatinine ≤1.5 ULN.

         13. Serum potassium within normal range.

         14. If female of child-bearing potential (i.e. not postmenopausal or surgically sterile),
             must be willing to abstain from sexual intercourse or employ an effective barrier or
             medical method of contraception during the study drug administration and for at least
             6 months following last treatment. If male, must be sterile or willing to abstain from
             sexual intercourse or employ a barrier method of contraception during the study
             treatment and for at least 6 months following last treatment.

        General Phase 1 and 2 Exclusion Criteria:

          1. Patients with primary central nervous system (CNS) cancer.

          2. Patients with QTc interval >450 msec for male and >470 msec for female.

          3. Patients who are on treatment with drugs known to prolong the QT/QTc interval.

          4. Patients who are being treated with Valproic Acid for any of its indication (epilepsy,
             mood disorder) must be excluded or must stop using the medication.

          5. Any serious medical condition that interferes with adherence to study procedures.

          6. Prior history of solid tumor malignancy diagnosed within the last three (3) years of
             study enrollment excluding adequately treated basal cell carcinoma of the skin,
             squamous cell carcinoma of the skin, or in situ cervical cancer, in situ breast
             cancer, in situ prostate cancer (patients must have shown no evidence of active
             disease for 2 years prior to enrollment)

          7. Pregnant or breast feeding females.

          8. New York Heart Association (NYHA) stage III/IV congestive heart failure, arrhythmias
             not adequately controlled, or other significant co-morbidities [e.g. active infection
             requiring systemic therapy, history of human immunodeficiency virus (HIV) infection,
             or active Hepatitis B or Hepatitis C].

          9. Use of other investigational agents within 30 days or 5 half-lives prior to the first
             dose of study drug. As long as patient has recovered from any related toxicities ≥
             Grade 1.

         10. Steroid treatment within seven (7) days prior to study treatment. Patients that
             require intermittent use of bronchodilators, topical steroids or local steroid
             injections will not be excluded from the study. Patients who have been stabilized to
             10 mg Prednisolone PO QD (or equivalent), daily (or less) at least seven (7) days
             prior to study drug administration are allowed.

        Phase 2 Tumor-specific Eligibility Criteria

        Phase 2 patients must meet the cohort-specific inclusion/exclusion criteria in addition to
        the general inclusion/exclusion criteria for Phase 1 and Phase 2 study listed above.

        Cohort 1: Patient Population: Relapsed/Refractory SCLC

          1. Histologically or cytologically confirmed limited or extensive disease stage of SCLC.
             The disease should be progressing during or relapsing after the previous treatment.

          2. At least one line of prior combination and no other standard therapy with proven
             clinical benefit is available.

          3. At least 3 weeks or 5 half-lives, whichever is shorter, should have elapsed since
             prior treatment as long as the patient recovered from any related toxicities to ≤
             Grade 1.

          4. Prior radiotherapy is acceptable provided the patient has recovered from any
             radiotherapy related acute toxicities.

          5. Presence of measurable disease as defined by the RECIST version 1.1

        Cohort 2: Patient Population: Relapsed/Refractory Soft Tissue Sarcoma or Non-Kit GIST

          1. Histologically confirmed diagnosis of advanced, unresectable, or metastatic soft
             tissue sarcoma not amenable to curative treatment with surgery or radiotherapy
             excluding:

             chondrosarcoma, neuroblastoma, osteosarcoma, embryonal rhabdomyosarcoma, or Kaposi
             sarcoma.

          2. Must have received at least one prior line chemotherapy regimen and no other standard
             therapy with proven clinical benefit is available.

          3. The disease should be progressing/relapsed during or after the previous treatment. At
             least 3 weeks should have elapsed since prior chemotherapy or 5 half-lives, whichever
             is shorter, as long as the patient recovered from any related toxicities to ≤ Grade 1.

          4. Presence of measurable disease as defined by RECIST version 1.1

        Cohort 3: Patient Population: Relapsed/Refractory Triple Negative Breast Cancer

          1. Histologically or cytologically confirmed locally advanced or metastatic Triple
             Negative Breast Cancer.

          2. Must have received at least one line of chemotherapy and no other standard therapy
             with proven clinical benefit is available. At least 3 weeks should have Elapsed since
             prior chemotherapy or 5 half-lives, whichever is shorter, as long as the patient
             recovered from acute toxicity of previous therapies to ≤ grade 1.

          3. Prior radiotherapy is acceptable provided it was applied within 4 four weeks before
             starting of this trial and the patient recovered from any radiotherapy related acute
             toxicities.

          4. The disease should be progressing/relapsed during or after the previous treatment.

          5. Presence of measurable disease as defined by RECIST version 1.1

        Cohort 4: Patient Population: Relapsed/Refractory Ovarian Cancer

          1. Histologically or cytologically confirmed advanced ovarian cancer: epithelial ovarian
             cancer, primary peritoneal cancer or fallopian tube cancer (excluding borderline
             ovarian cancer) that is resistant or refractory to platinum therapy and no other
             standard therapy with proven clinical benefit is available.

               1. Platinum-resistant ovarian cancer is defined as disease that responded to primary
                  platinum therapy and then progressed within 6 months or disease that progressed
                  during or within six months of completing a subsequent platinum therapy.

               2. Primary platinum refractory disease is defined as disease that has not responded
                  to a platinum-based regimen or experienced disease recurrence within 3 months of
                  completing a first-line platinum-based regimen.

          2. The disease should be progressing/relapsed during or after the previous treatment. At
             least 3 weeks should have elapsed since prior chemotherapy or 5 half-lives, whichever
             is shorter, as long as the patient recovered from acute toxicity of previous therapies
             to ≤ Grade 1.

          3. Presence of measurable disease as defined by RECIST version 1.1
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety: Number of participants with treatment-related adverse events as assessed by CTCAE V4.03
Time Frame:12 months from beginning phase 1
Safety Issue:
Description:Safety: Number of patients experiencing treatment-related adverse events as assessed by CTCAE v4.03.

Secondary Outcome Measures

Measure:PK: Maximum Plasma Concentration [Cmax]
Time Frame:12 months from beginning phase 1
Safety Issue:
Description:Maximum plasma concentration of EDO-S101
Measure:PK: Time to reach maximum (peak) plasma concentration following drug administration (Tmax)
Time Frame:12 months from beginning phase 1
Safety Issue:
Description:Tmax of EDO-S101
Measure:PK: Area Under the Curve [AUC]
Time Frame:12 months from beginning phase 1
Safety Issue:
Description:EDO-S101 AUC in plasma
Measure:PK: Elimination half-life [t½,]
Time Frame:12 months from beginning phase 1
Safety Issue:
Description:PK: Half-life [t½,] for EDO-S101
Measure:Response Rate: Progression Free Survival (PFS)
Time Frame:12 months from beginning phase 2
Safety Issue:
Description:PFS : Will be measured from the start of treatment with EDO-S101 until the first documentation of disease progression or death due to any cause whichever occurs first
Measure:Response Rate: Overall Survival (OS)
Time Frame:12 months from beginning phase 2
Safety Issue:
Description:OS will be determined as the time from the start of treatment with EDO-S101 until death due to any cause.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Mundipharma-EDO GmbH

Trial Keywords

  • Phase 1 clinical trial
  • Solid Tumor
  • Small Cell Lung Cancer
  • Breast Cancer
  • Ovarian Cancer
  • Soft Tissue Sarcoma
  • Relapsed/Refractory
  • Triple Negative
  • GIST
  • Epithelial cancer
  • Peritoneal cancer
  • Fallopian tube cancer
  • Metastatic
  • Advanced

Last Updated

November 15, 2017