Small Cell Lung CancerPhase 1/2EDO-S101NCT03345485
Study of the Safety, Pharmacokinetics and Efficacy of Tinostamustine in Patients With Advanced Solid Tumors.
A Phase 1/2 study testing Tinostamustine 60mg/m2 over 30min, Tinostamustine 80mg/m2 over 30min and Tinostamustine 100mg/m2 over 30min in people with Small Cell Lung Cancer and Soft Tissue Sarcoma, run by Mundipharma Research Limited at 13 sites in 5 countries.
Trial summary
Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer, Soft Tissue Sarcoma, Triple-negative Breast Cancer
- What is being tested?
- Tinostamustine 60mg/m2 over 30min, Tinostamustine 80mg/m2 over 30min and Tinostamustine 100mg/m2 over 30min
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 8 Nov 2017to 29 Mar 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- To be eligible to participate in the trial, a patient cannot meet any of the following exclusion criteria:
- Patients with primary central nervous system (CNS) cancer.
- Patients with QTc interval (Fridericia's formula) >450 msec.
- Patients who are on treatment with drugs known to prolong the QT/QTc interval.
- Patients who are being treated with Valproic Acid for any of its indication (epilepsy, mood disorder).
- Any serious medical condition that interferes with adherence to trial procedures.
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- 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)
- Pregnant or breast feeding females.
- 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].
- Use of other investigational agents within 28 days prior to the first dose of study drug, provided the patient has recovered from any related toxicities ≥Grade 1.
- Steroid treatment within seven (7) days prior to trial 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 orally (PO) once daily (QD) (or equivalent), daily (or less) at least seven (7) days prior to IMP administration are allowed.
- 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: Relapsed/Refractory small cell lung cancer (SCLC)
- Histologically or cytologically confirmed limited or extensive disease stage of SCLC.
- Must have received at least 1 line of prior combination chemotherapy or biological 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.
- At least 28 days should have elapsed since prior treatment as long as the patient has recovered from any related toxicities to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
- Prior radiotherapy is acceptable provided the patient has recovered from any radiotherapy related acute toxicities.
- The disease should be progressing during or relapsing after the previous treatment.
- Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
- Cohort 2: Relapsed/Refractory Soft Tissue Sarcoma (STS)
- Histologically confirmed diagnosis of advanced, unresectable, or metastatic soft tissue sarcoma not amenable to curative treatment with surgery or radiotherapy excluding: neuroblastoma, GIST, embryonal rhabdomyosarcoma, Kaposi sarcoma, chondrosarcoma, osteosarcoma or Ewing's sarcoma.
- Must have received at least one prior line prior line chemotherapy or biological therapy 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. At least twenty-eight (28) days should have elapsed since prior chemotherapy, as long as the patient recovered from any related toxicities to ≤ Grade 1 (or ≤Grade 2 for any symptomatic neuropathy or endocrinopathies).
- The disease should be progressing during or relapsing after the previous treatment.
- Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
- Cohort 3: Relapsed/Refractory Triple Negative Breast Cancer (TNBC)
- Histologically or cytologically confirmed locally advanced or metastatic Triple Negative Breast Cancer. Proven human epidermal growth factor receptor 2 (HER2) negative by immunohistochemistry (INH) or in situ hybridization (ISH) per per American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) guidelines.
- Must have received at least one (1) line of chemotherapy or biological therapy and no other standard therapy with proven clinical benefit was available or recommended based on the Investigator's individual risk-benefit assessment for the subject.
- At least three (3) weeks should have elapsed since prior chemotherapy as long as the subject recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
- Prior radiotherapy was acceptable provided it was administered at least four (4) weeks (two (2) weeks for palliative, limited field radiation therapy) prior to starting treatment on this study and the subject recovered from any radiotherapy related acute toxicities.
- The disease had to be progressing during or relapsing after the previous treatment.
- Presence of measurable disease as defined by RECIST version 1.1. Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, were usually not considered measurable unless there had been demonstrated progression in the lesion.
- Cohort 4: Patient Population: Relapsed/Refractory Ovarian Cancer (OC)
- Histologically or cytologically confirmed advanced ovarian cancer: epithelial ovarian cancer, including primary peritoneal cancer or fallopian tube cancer (excluding borderline ovarian cancer, MMMT) of high grade serous histology, or high grade endometrioid 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. Clear cell carcinomas are excluded. Patients with primary platinum refractory disease (failure to respond to initial platinum treatment or relapse within four (4) weeks) and patients with primary platinum resistant disease (progression within six (6) months of completing first line platinum-based therapy) are excluded from the study.
- At least twenty eight (28) days should have elapsed since prior chemotherapy as long as the patient recovered from acute toxicity of previous therapies to ≤ Grade 1 (or ≤ Grade 2 for any symptomatic neuropathy or endocrinopathies).
- The disease should be progressing during or relapsing after the previous treatment.
- Presence of measurable disease as defined by RECIST version 1.1. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion.
- Cohort 5: Relapsed/Refractory Endometrial Cancer (EC)
- Histologically or cytologically confirmed locally advanced or metastatic endometrial cancer (excluding leiomyosarcoma and carcinosarcoma)
- Must have received at least one (1) 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 three (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).
- Prior radiotherapy is acceptable provided it was administered at least four(4) weeks (two (2) weeks for palliative, limited field radiation therapy) prior to starting treatment on this trial and recovered from any radiotherapy related acute toxicities.
- The disease should be progressing/relapsed during or after the previous treatment.
- Presence of measurable disease as defined by RECIST version 1.1. Tumour lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, were usually not considered measurable unless there had been demonstrated progression in the lesion.
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
United States5 sites
University of Michigan
Ann Arbor, Michigan, 48109
Mary Crowley Cancer Research
Dallas, Texas, 75251
Cedars-Sinai Medical Center
Los Angeles, California, 90048
New York University
New York, New York, 10016
Stanford University Medical Center
Palo Alto, California, 94304
Canada3 sites
Juravinski Cancer Centre
Hamilton, Ontario, on, L8V 1C3
McGill University
Montreal, Quebec, H4A 3J1
BC Cancer-Vancouver
Vancouver, Vancouver, BC, V5Z 1M9
Italy2 sites
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
Istituto Europeo di Oncologia
Milan, MI 20141
Spain2 sites
Hospital Universitari Vall d'Hebron
Barcelona, Horta-Guinardó, 08035
Hospital Universitario La Paz
Madrid, Fuencarral-El Pardo, 28046
About this study
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. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 60mg/m2 Administered During a 60 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 80mg/m2 Administered During a 80 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors.
Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. The main purpose of this study is to assess the safety, tolerability and efficacy of Tinostamustine in subjects with advanced solid tumours. Subjects will be given Tinostamustine via intravenous infusion on Days 1 and 15 of a 4-week cycle, the dose and infusion time will vary depending on the phase of the study.
Read the detailed description
The study consists of 2 phases and 2 sub-studies:
This study is a multi-centre, open-label phase 1/2 study of single agent EDO-S101 in subjects with advanced solid tumours.
Phase 1 part of the study is designed to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and the Pharmacokinetic (PK) of EDO-S101 as a single agent in patients with solid tumours who have progressed after at least one (1) line of therapy and for whom no other standard therapy with proven clinical benefit is available.
Phase 2 part of the study is designed to evaluate the overall response rate (ORR) of the RP2D, plus the rate of patients with stable disease (SD) at 4 or 6 months, depending on the type of solid tumour. The RP2D was determined after phase 1 to be 80 mg/m2 of EDO-S101 administered over 1 hour on Day 1 and Day 15 of each 4-week treatment cycle.
In addition, two sub-studies are designed to better characterize the effect of EDO-S101: one at a dose of 60 mg/m2 administered over 60 minutes and the second at a dose of 80 mg/m2 administered over 80 minutes on cardiac repolarization (QTc) and other ECG parameters in the subjects with solid tumours.
Subjects were eligible for these studies if they had a histologically confirmed solid tumour, signed informed consent and met the inclusion/exclusion criteria. After providing informed consent, subjects were screened, and all procedures were performed as per protocol.
- Conditions
- Small Cell Lung Cancer, Soft Tissue Sarcoma, Triple-negative Breast Cancer, Ovarian Cancer, Endometrial Cancer
- Being tested
- Tinostamustine 60mg/m2 over 30min, Tinostamustine 80mg/m2 over 30min, Tinostamustine 100mg/m2 over 30min, Tinostamustine 60mg/m2 over 60min, Tinostamustine 80mg/m2 over 60min
- Keywords
- Phase 1 (P1), Solid Tumor, Small Cell Lung Cancer (SCLC), Breast Cancer, Ovarian Cancer (OC), Soft Tissue Sarcoma (STS), Relapsed/Refractory, Triple Negative, Gastrointestinal stromal tumors (GIST), Epithelial cancer, Peritoneal cancer, Fallopian tube cancer, Metastatic, Advanced, Endometrial Cancer (EC), Phase 2 (P2), Corrected QT interval (QTc), System Organ Class (SOC), Preferred Term (PT), Day 1 (D1)
- Medical subject headings
- Small Cell Lung Carcinoma, Sarcoma, Triple Negative Breast Neoplasms, Ovarian Neoplasms, Endometrial Neoplasms, Breast Neoplasms, Recurrence, Gastrointestinal Stromal Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tinostamustine 60mg/m2 over 30minDrug
Also called EDO-S101
Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
Tinostamustine 80mg/m2 over 30minDrug
Also called EDO-S101
Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
Tinostamustine 100mg/m2 over 30minDrug
Also called EDO-S101
Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle.
Tinostamustine 60mg/m2 over 60minDrug
Also called EDO-S101
Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
Tinostamustine 80mg/m2 over 60minDrug
Also called EDO-S101.
Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
Tinostamustine 100mg/m2 over 60minDrug
Also called EDO-S101
Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle.
Tinostamustine 80mg/m2 over 80minDrug
Also called EDO-S101
Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 80 minutes on Days (D) 1 and 15 of each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 min) cohort 1 | Experimental | Not described Receives: Drug: Tinostamustine 60mg/m2 over 30min |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 min) cohort 2 | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 30min |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 min) cohort 3 | Experimental | Not described Receives: Drug: Tinostamustine 100mg/m2 over 30min |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 min) cohort 4 | Experimental | Not described Receives: Drug: Tinostamustine 60mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 min) cohort 5 | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 min) cohort 6 | Experimental | Not described Receives: Drug: Tinostamustine 100mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Small Cell Lung Cancer (SCLC) cohort | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Soft Tissue Sarcoma (STS) cohort | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Triple Negative breast Cancer (TNBC) cohort | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Ovarian Cancer (OC) cohort | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Endometrial Cancer (EC) cohort | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Sub study 1 (SS1) | Experimental | Not described Receives: Drug: Tinostamustine 60mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Sub study 2 (SS2) | Experimental | Not described Receives: Drug: Tinostamustine 80mg/m2 over 80min |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1
All TEAEs was reported from the first dose of study drug through the time of study drug discontinuation (at any time or Day 28 of the last treatment Cycle). All treatment-related TEAEs was followed until resolution or stabilization. For the purpose of regulatory reporting requirements, causal relationships of definite, probable, and possible was considered treatment-related.
Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03. (June 2010).
Measured: From each patient's time of first dose administration to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 6 months.
Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2
The Clinical Benefit Response Rate is calculated as the number of patients with Clinical Benefit Response divided by number of patients in the FAS (in the respective cohort). Clinical Benefit Response is defined as patients achieving stable disease with a duration of at least 12 weeks (84 days).
Summary subjects analysed were 36.
Measured: From start treatment and assessed after every 2 cycles until determination of stable disease and follow up for up to 84 days.
Highest Change From Baseline in QTcF in Sub-studies
QTcF: corrected QT interval [QTc] using Fridericia's formula) and other electrocardiogram (ECG) parameters in subjects with solid tumours who have progressed after at least 1 line of therapy and for whom no other standard therapy with proven clinical benefit is available.
Within each cycle a Change from baseline (CfB) is calculated for QTcF relative to the baseline value of day 1 of the cycle. QTcF CfB= QTcF Post-dose value - QTcF pre-dose value of D1 ECG Parameters: 4-hours ECG holter monitoring in C1 and ECGs during EDO-S101 administration.
Continuous variables the mean and standard deviation are presented together with the total number of observations and the number of missing and non-missing values.
Measured: From cycle 1 and at every cycle on treatment days D1 and D15, assessed pre-dose and post-start of infusion at 30 and 80mins (Substudy 2 - up to 6 months) and 30, 60, 90, 120 and 180mins (substudy 1 - up to 6 months).
Secondary outcomes (11)
Treatment-related Adverse Events on Phase 2 and Sub Studies
Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03, June 2010, with the exception that assessment of QTc prolongations constituting adverse events (AEs) of special interest were based on NCI CTCAE version 5.0, November 2017.
All subjects who received at least 1 dose of study treatment were included in the Safety Population. Safety analyses were performed on data from all subjects in the Safety Population.
Adverse events are reported on a patient basis. The percentages are calculated using the number of patients in the Safety Analysis Set as the denominator.
Measured: From each patient's time of informed consent to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 8 months
Progression Free Survival (PFS) Time for Phase 2 and Sub Studies
PFS was defined as the number of days between the date of the first dose of treatment of a patient and the first date of disease progression, start of a subsequent anti-cancer therapy, or death of the patient.
Measured: From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 26 months.
Overall Survival (OS) Time for Phase 2 and Sub Studies
Overall survival is defined as the number days between the date of the first dose of treatment and the date of death. If no date of death is recorded the Overall Survival time is censored at the Last available visit date.
Phase 2: To determine the overall survival (OS) time for subjects with solid tumours.
SS1:To determine the overall survival (OS) time for subjects who received 60 mg/m2 of EDO-S101 during a 60-minute Infusion.
SS2: To determine the overall survival (OS) time for subjects who received 80 mg/m2 of EDO-S101 during a 80-minute Infusion.
Measured: From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 42 months.
Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies
The duration of objective response is measured from the date of the first tumor response assessment with an Investigator's Overall Response of CR or PR (whichever status is recorded first) until the date of progression or death. DoR is presented by subject.
Measured: From patient's first overall response of CR or PR, until disease progression/subsequent anti-cancer therapy/death from any cause, up to 24 months.
Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies
To determine the objective response rate (ORR) and the clinical benefit rate (CBR [Complete Response (CR), Partial Response (PR) plus durable Stable Disease (SD)]) in Sub Studies.
SD was regarded as durable if, after observing SD, the first observation of PD was at least 84 days after the start of study treatment.
Measured: From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months)
Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies.
Duration of SD, was defined as the number of days between the date of the first dose of treatment and the first date of disease progression or death.
SD was regarded as durable if, after observing SD, the first observation of progression disease was at least 84 days after the start of study treatment.
Measured: From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months).
Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies
Measured: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies.
Measured: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Summary of Tmax in in Phase 2 and Sub Studies.
Measured: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies
Measured: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Summary of Half-life of Tinostamustine in Phase 2 and Substudies.
Measured: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start8 Nov 2017
- Primary completion27 Jul 2022
- Study completion29 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- In phase 1 (dose escalation phase) of the study, subjects were allocated sequentially. In phase 2, subjects were allocated in parallel to the various arms (cohorts) based on their cancer specifics. In the substudies 1 and 2, subjects were allocated into a single group in each substudy. Overall, the study model is described as Sequential as the study proceeded in phases.
- Masking
- None (open label)
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mundipharma Research Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Shivaani Kummar, MD, Principal investigator, Oregon Health and Science UniversityAna Oaknin, MD, Principal investigator, Head of Gynaecologic Cancer Program, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03345485
- Sponsor's protocol ID
- EDO-S101-1002
- Other IDs
- 2020-004246-11
- Acronym
- EDO-S101
- Status last verified
- Jun 2024
- First submitted
- 24 Oct 2017
- Last updated
- 21 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Relevant patient listing data of de-identified patients may be reviewed
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 60mg/m2 Administered During a 60 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors. Sub-study to Characterize the Effects of Tinostamustine at a Dose of 80mg/m2 Administered During a 80 Minutes Infusion on Cardiac Repolarization, in Patients With Advanced Solid Tumors.
- ClinicalTrials.gov ID
- NCT03345485
- Acronym / sponsor ID
- EDO-S101 / EDO-S101-1002
- Conditions
- Small Cell Lung Cancer, Soft Tissue Sarcoma, Triple-negative Breast Cancer, Ovarian Cancer, Endometrial Cancer
- Keywords
- Phase 1 (P1), Solid Tumor, Small Cell Lung Cancer (SCLC), Breast Cancer, Ovarian Cancer (OC), Soft Tissue Sarcoma (STS), Relapsed/Refractory, Triple Negative
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Mundipharma Research LimitedIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2017 (actual)
- Primary completion
- 27 Jul 2022 (actual)
- Study completion
- 29 Mar 2023 (actual)
- First posted
- 17 Nov 2017 (actual)
- Results
- Posted 21 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Tinostamustine (EDO-S101) is a first-in-class alkylating deacetylase inhibitor designed to improve drug access to deoxyribonucleic acid (DNA) strands, induce DNA damage and counteract its repair in cancer cells. The main purpose of this study is to assess the safety, tolerability and efficacy of Tinostamustine in subjects with advanced solid tumours. Subjects will be given Tinostamustine via intravenous infusion on Days 1 and 15 of a 4-week cycle, the dose and infusion time will vary depending on the phase of the study.
Detailed description
The study consists of 2 phases and 2 sub-studies:
This study is a multi-centre, open-label phase 1/2 study of single agent EDO-S101 in subjects with advanced solid tumours.
Phase 1 part of the study is designed to determine the safety, tolerability, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D) and the Pharmacokinetic (PK) of EDO-S101 as a single agent in patients with solid tumours who have progressed after at least one (1) line of therapy and for whom no other standard therapy with proven clinical benefit is available.
Phase 2 part of the study is designed to evaluate the overall response rate (ORR) of the RP2D, plus the rate of patients with stable disease (SD) at 4 or 6 months, depending on the type of solid tumour. The RP2D was determined after phase 1 to be 80 mg/m2 of EDO-S101 administered over 1 hour on Day 1 and Day 15 of each 4-week treatment cycle.
In addition, two sub-studies are designed to better characterize the effect of EDO-S101: one at a dose of 60 mg/m2 administered over 60 minutes and the second at a dose of 80 mg/m2 administered over 80 minutes on cardiac repolarization (QTc) and other ECG parameters in the subjects with solid tumours.
Subjects were eligible for these studies if they had a histologically confirmed solid tumour, signed informed consent and met the inclusion/exclusion criteria. After providing informed consent, subjects were screened, and all procedures were performed as per protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 13
- Model description
- In phase 1 (dose escalation phase) of the study, subjects were allocated sequentially. In phase 2, subjects were allocated in parallel to the various arms (cohorts) based on their cancer specifics. In the substudies 1 and 2, subjects were allocated into a single group in each substudy. Overall, the study model is described as Sequential as the study proceeded in phases.
| Arm | Type | Receives |
|---|---|---|
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 min) cohort 1 | Experimental | Drug: Tinostamustine 60mg/m2 over 30min |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 min) cohort 2 | Experimental | Drug: Tinostamustine 80mg/m2 over 30min |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 min) cohort 3 | Experimental | Drug: Tinostamustine 100mg/m2 over 30min |
| Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 min) cohort 4 | Experimental | Drug: Tinostamustine 60mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 min) cohort 5 | Experimental | Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 min) cohort 6 | Experimental | Drug: Tinostamustine 100mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Small Cell Lung Cancer (SCLC) cohort | Experimental | Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Soft Tissue Sarcoma (STS) cohort | Experimental | Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Triple Negative breast Cancer (TNBC) cohort | Experimental | Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Ovarian Cancer (OC) cohort | Experimental | Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Endometrial Cancer (EC) cohort | Experimental | Drug: Tinostamustine 80mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Sub study 1 (SS1) | Experimental | Drug: Tinostamustine 60mg/m2 over 60min |
| Tinostamustine (EDO-S101) - Sub study 2 (SS2) | Experimental | Drug: Tinostamustine 80mg/m2 over 80min |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (43 listed)
- To be eligible to participate in the trial, a patient cannot meet any of the following exclusion criteria:
- Patients with primary central nervous system (CNS) cancer.
- Patients with QTc interval (Fridericia's formula) >450 msec.
- Patients who are on treatment with drugs known to prolong the QT/QTc interval.
- Patients who are being treated with Valproic Acid for any of its indication (epilepsy, mood disorder).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tinostamustine 60mg/m2 over 30minAlso: EDO-S101Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (30 min) cohort 1 |
| Tinostamustine 80mg/m2 over 30minAlso: EDO-S101Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (30 min) cohort 2 |
| Tinostamustine 100mg/m2 over 30minAlso: EDO-S101Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 30 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (30 min) cohort 3 |
| Tinostamustine 60mg/m2 over 60minAlso: EDO-S101Tinostamustine as a single agent was administered at doses of 60mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Phase 1 - 60mg/m2 (60 min) cohort 4, Tinostamustine (EDO-S101) - Sub study 1 (SS1) |
| Tinostamustine 80mg/m2 over 60minAlso: EDO-S101.Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Phase 1 - 80mg/m2 (60 min) cohort 5, Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Endometrial Cancer (EC) cohort, Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Ovarian Cancer (OC) cohort, Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Small Cell Lung Cancer (SCLC) cohort, Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Soft Tissue Sarcoma (STS) cohort, Tinostamustine (EDO-S101) - Phase 2 Relapsed/refractory Triple Negative breast Cancer (TNBC) cohort |
| Tinostamustine 100mg/m2 over 60minAlso: EDO-S101Tinostamustine as a single agent was administered at doses of 100mg/m2 by intravenous infusion over 60 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Phase 1 - 100mg/m2 (60 min) cohort 6 |
| Tinostamustine 80mg/m2 over 80minAlso: EDO-S101Tinostamustine as a single agent was administered at doses of 80mg/m2 by intravenous infusion over 80 minutes on Days (D) 1 and 15 of each 28-day cycle. | Drug | Tinostamustine (EDO-S101) - Sub study 2 (SS2) |
Primary outcome
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1
Time frame: From each patient's time of first dose administration to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 6 months.
All TEAEs was reported from the first dose of study drug through the time of study drug discontinuation (at any time or Day 28 of the last treatment Cycle). All treatment-related TEAEs was followed until resolution or stabilization. For the purpose of regulatory reporting requirements, causal relationships of definite, probable, and possible was considered treatment-related. Number of patients experiencing treatment-related adverse events (TEAE) as assessed by CTCAE v4.03. (June 2010).
Clinical Benefit Response Rate in Selected Solid Tumor Cohorts on Phase 2
Time frame: From start treatment and assessed after every 2 cycles until determination of stable disease and follow up for up to 84 days.
The Clinical Benefit Response Rate is calculated as the number of patients with Clinical Benefit Response divided by number of patients in the FAS (in the respective cohort). Clinical Benefit Response is defined as patients achieving stable disease with a duration of at least 12 weeks (84 days). Summary subjects analysed were 36.
Highest Change From Baseline in QTcF in Sub-studies
Time frame: From cycle 1 and at every cycle on treatment days D1 and D15, assessed pre-dose and post-start of infusion at 30 and 80mins (Substudy 2 - up to 6 months) and 30, 60, 90, 120 and 180mins (substudy 1 - up to 6 months).
QTcF: corrected QT interval [QTc] using Fridericia's formula) and other electrocardiogram (ECG) parameters in subjects with solid tumours who have progressed after at least 1 line of therapy and for whom no other standard therapy with proven clinical benefit is available. Within each cycle a Change from baseline (CfB) is calculated for QTcF relative to the baseline value of day 1 of the cycle. QTcF CfB= QTcF Post-dose value - QTcF pre-dose value of D1 ECG Parameters: 4-hours ECG holter monitoring in C1 and ECGs during EDO-S101 administration. Continuous variables the mean and standard deviation are presented together with the total number of observations and the number of missing and non-missing values.
11 secondary outcomes
Treatment-related Adverse Events on Phase 2 and Sub Studies
Time frame: From each patient's time of informed consent to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 8 months
Progression Free Survival (PFS) Time for Phase 2 and Sub Studies
Time frame: From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 26 months.
Overall Survival (OS) Time for Phase 2 and Sub Studies
Time frame: From patient's first dose until first documented progression/start of subsequent anti-cancer therapy/death from any cause, whichever came first, up to 42 months.
Maximum Duration of Response (DoR) Time for Phase 2 and Sub Studies
Time frame: From patient's first overall response of CR or PR, until disease progression/subsequent anti-cancer therapy/death from any cause, up to 24 months.
Objective Response Rate (ORR) and the Clinical Benefit Rate (CBR) That Persists for at Least Four (4) Months in Selected Solid Tumor Cohorts on Sub Studies
Time frame: From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months)
Number of Participants With Duration of Stable Disease (SD) That Persists for at Least 4 Months in Selected Solid Tumor Cohorts in Sub Studies.
Time frame: From start of treatment, assessed every 2 cycles, until first documented complete CR, PR or SD, up to 6 months. If SD, assessment continued every 2 cycles until CR/PR/death (up to 6 months).
Maximum Plasma Concentration (Cmax) in Phase 2 and Sub Studies
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Area Under the Curve [AUC(0-t)] in Phase 2 and Sub Studies.
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Summary of Tmax in in Phase 2 and Sub Studies.
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Clearance of Tinostamustine and Metabolites in Phase 2 and Substudies
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Summary of Half-life of Tinostamustine in Phase 2 and Substudies.
Time frame: Blood samples were collected over a period of 24hr (phase 2 and sub-study 1) and 30hr (sub-study 2) on Cycle 1 Day 1 and Day 15.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Relevant patient listing data of de-identified patients may be reviewed
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shivaani Kummar, MD principal investigator
Oregon Health and Science University
Ana Oaknin, MD principal investigator
Head of Gynaecologic Cancer Program, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d'Hebron
13 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Tinostamustine 60mg/m2 over 30min, Tinostamustine 80mg/m2 over 30min and Tinostamustine 100mg/m2 over 30min in people with Small Cell Lung Cancer and Soft Tissue Sarcoma, run by Mundipharma Research Limited at 13 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Canada, Italy, Spain, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE V4.03 on Phase 1 (time frame: From each patient's time of first dose administration to discontinuation of study drug (at any time or D28 of the last treatment cycle), up to 6 months.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2024.