Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03345485
Other study ID # EDO-S101-1002
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date October 6, 2017
Est. completion date March 29, 2023

Study information

Verified date September 2023
Source Mundipharma Research Limited
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Tinostamustine (EDO-S101) is a new chemical entity, an AK-DAC (a first-in-class alkylating deacetylase inhibiting molecule), that in pre-clinical 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.


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 EDO-S101. The Phase 1 portion of the study is designed to define the MTD by evaluating toxicities during dose escalation until MAD. The Phase 2 portion of the study is designed to evaluate ORR and SD that persists for at least 4 months of the RP2D.


Recruitment information / eligibility

Status Completed
Enrollment 71
Est. completion date March 29, 2023
Est. primary completion date July 27, 2022
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 or recommended based on the investigator's individual risk-benefit as-sessment for the patient. 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 or recommended based on the investigator's individual risk-benefit assessment for the patient. 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 (or = Grade 2 for any symptomatic neuropathy or endocrinopathies). 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 1. Histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy excluding: neuroblastoma, 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 or recommended based on the investigator's individual risk-benefit assessment for the patient. For GIST-patients: must have received at least two lines of tyrosine kinase inhibitors or do not respond to or for which tyrosine kinase inhibitor therapy is not suitable. 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 (or = Grade 2 for any symptomatic neuropathy or endocrinopathies). 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. Proven HER2 negative by immunohistochemistry (IHC) or in situ hybridization (ISH) per ASCO-CAP guidelines. 2. Must have received at least one line of chemotherapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. 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 (or = Grade 2 for any symptomatic neuropathy or endocrinopathies). 3. Prior radiotherapy is acceptable provided it was applied within 4 four weeks (2 weeks for palliative, limited field radiation therapy) prior to starting treatment on 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 or recommended based on the investigator's individual risk-benefit assessment for the patient. 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 (or = Grade 2 for any symptomatic neuropathy or endocrinopathies). 3. Presence of measurable disease as defined by RECIST version 1.1 Cohort 5: Relapsed/Refractory Endometrial Cancer 1. Histologically or cytologically confirmed locally advanced or metastatic endometrial cancer. 2. Must have received at least one line of chemotherapy and no other standard therapy with proven clinical benefit is available or recommended based on the investigator's individual risk-benefit assessment for the patient. 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 (or = Grade 2 for any symptomatic neuropathy or endocrinopathies). 3. Prior radiotherapy is acceptable provided it was administered at least 4 weeks (2 weeks for palliative, limited field radiation therapy) prior to starting treatment on this trial and 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.

Study Design


Intervention

Drug:
Tinostamustine (EDO-S101)
The study is designed as an open label, Phase 1/2 trial of single agent EDO-S101. The Phase 1 portion of the study is designed to define the MTD by evaluating toxicities during dose escalation until MAD. The Phase 2 portion of the study is designed to evaluate ORR and SD that persists for at least 4 months of the RP2D.

Locations

Country Name City State
Canada McGill University Montréal Quebec
United States University of Michigan Ann Arbor Michigan
United States Northwestern University Chicago Illinois
United States Mary Crowley Cancer Research Dallas Texas
United States Cedars-Sinai Medical Center Los Angeles California
United States New York Univesity New York New York
United States Stanford University Medical Center Palo Alto California
United States Georgetown University Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Mundipharma Research Limited

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety: Number of participants with treatment-related adverse events as assessed by CTCAE V4.03 Safety: Number of patients experiencing treatment-related adverse events as assessed by CTCAE v4.03. 12 months from beginning phase 1
Primary Objective Response Rate (ORR) and SD that persists for at least 4 months in selected solid tumor cohorts ORR is defined as proportion of subjects with CR or PR based on RECIST V.1.1 12 months from beginning phase 2
Secondary PK: Maximum Plasma Concentration [Cmax] Maximum plasma concentration of EDO-S101 12 months from beginning phase 1
Secondary PK: Time to reach maximum (peak) plasma concentration following drug administration (Tmax) Tmax of EDO-S101 12 months from beginning phase 1
Secondary PK: Area Under the Curve [AUC] EDO-S101 AUC in plasma 12 months from beginning phase 1
Secondary PK: Elimination half-life [t½] PK: Half-life [t½] for EDO-S101 12 months from beginning phase 1
Secondary Response Rate: Progression Free Survival (PFS) 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 12 months from beginning phase 2
Secondary Response Rate: Overall Survival (OS) OS will be determined as the time from the start of treatment with EDO-S101 until death due to any cause. 12 months from beginning phase 2
See also
  Status Clinical Trial Phase
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Withdrawn NCT05201001 - APX005M in Patients With Recurrent Ovarian Cancer Phase 2
Completed NCT02963831 - A Study to Investigate ONCOS-102 in Combination With Durvalumab in Subjects With Advanced Peritoneal Malignancies Phase 1/Phase 2
Not yet recruiting NCT06376253 - A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers Phase 1
Recruiting NCT05489211 - Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03) Phase 2
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Active, not recruiting NCT03667716 - COM701 (an Inhibitor of PVRIG) in Subjects With Advanced Solid Tumors. Phase 1
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Recruiting NCT05156892 - Tamoxifen and SUBA-Itraconzole Combination Testing in Ovarian Cancer Phase 1
Suspended NCT02432378 - Intensive Locoregional Chemoimmunotherapy for Recurrent Ovarian Cancer Plus Intranodal DC Vaccines Phase 1/Phase 2
Recruiting NCT04533763 - Living WELL: A Web-Based Program for Ovarian Cancer Survivors N/A
Active, not recruiting NCT03371693 - Cytoreductive Surgery(CRS) Plus Hyperthermic Intraperitoneal Chemotherapy(HIPEC) With Lobaplatin in Advanced and Recurrent Epithelial Ovarian Cancer Phase 3
Withdrawn NCT03032614 - Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients Phase 2
Completed NCT01936363 - Trial of Pimasertib With SAR245409 or Placebo in Ovarian Cancer Phase 2
Completed NCT02019524 - Phase Ib Trial of Two Folate Binding Protein Peptide Vaccines (E39 and J65) in Breast and Ovarian Cancer Patients Phase 1
Terminated NCT00788125 - Dasatinib, Ifosfamide, Carboplatin, and Etoposide in Treating Young Patients With Metastatic or Recurrent Malignant Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT05059522 - Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing Phase 3
Active, not recruiting NCT04383210 - Study of Seribantumab in Adult Patients With NRG1 Gene Fusion Positive Advanced Solid Tumors Phase 2
Terminated NCT04586335 - Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors. Phase 1
Terminated NCT03146663 - NUC-1031 in Patients With Platinum-Resistant Ovarian Cancer Phase 2