A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma

Blokhin Cancer Research Center (Moscow, Russia)

RUS · PI Dr. Moreau · 7 patients

Border Medical Oncology (Wodonga, Australia)

AUS · PI Dr. Kim · 1 patients

CTRC Institute for Drug Development, University of Texas (San Antonio, TX)

USA · PI Dr. Muller · 11 patients

Christian Medical College (Vellore, India)

IND · PI Dr. Dubois · 2 patients

Clinical County Hospital Mures, Medical Oncology Department (Târgu Mureş, Romania)

ROU · PI Dr. Silva · 4 patients

Curie Manavata Cancer Centre (Nashik, India)

IND · PI Dr. Nolan · 1 patients

Delhi State Cancer Institute (Mandoli, India)

IND · PI Dr. Muller · 2 patients

Delhi State Cancer Institute (Pune, India)

IND · PI Dr. Okafor · 0 patients

Epworth HealthCare Clinical Trials and Research Centre (Richmond, Australia)

AUS · PI Dr. Dubois · 3 patients

Hemato Oncology Clinic, Vedanta Institute of Medical Science (Ahmedabad, India)

IND · PI Dr. Ito · 4 patients

Hemato Oncology Clinic, Vedanta Institute of Medical Science (Thaltej, India)

IND · PI Dr. Moreau · 0 patients

Jehangir Clinical Development Centre Pvt Ltd (Pune, India)

IND · PI Dr. Tanaka · 1 patients

Lviv State Oncological Regional Treatment - Diagnostics Center, Chemotherapy Department (Lviv, Ukraine)

UKR · PI Dr. Okafor · 3 patients

M.S. Ramaiah Medical College and Hospitals (Bangalore, India)

IND · PI Dr. Reyes · 1 patients

Medisprof SRL (Cluj-Napoca, Romania)

ROU · PI Dr. Kowalski · 1 patients

Mount Medical Centre (Perth, Australia)

AUS · PI Dr. Jansen · 0 patients

Municipal Institution "Dnipropetrovsk City Multi-Field Clinical Hospital #4" of Dnipropetrovsk Regional Councel (Dnipropetrovsk, Ukraine)

UKR · PI Dr. Reyes · 2 patients

Municipal institution "Chernivtsi Regional Clinical Oncologic Dispensary" (Chernivtsi, Ukraine)

UKR · PI Dr. Ito · 1 patients

Noble Hospital Clinical Research Department 1st Floor (Hadapsar, India)

IND · PI Dr. Rossi · 1 patients

Oncological Institute "Prof. Dr. I. Chiricuta", Cluj-Napoca (Cluj-Napoca, Romania)

ROU · PI Dr. Novak · 3 patients

Pennsylvania Hematology Oncology Associates (Philadelphia, PA)

USA · PI Dr. Tanaka · 2 patients

Royal Hobart Hospital (Hobart, Australia)

AUS · PI Dr. Novak · 3 patients

Royal North Shore (St Leonards, Australia)

AUS · PI Dr. Rossi · 2 patients

Royal Perth Hospital (Perth, Australia)

AUS · PI Dr. Silva · 4 patients

Sarcoma Oncology Center (Santa Monica, CA)

USA · PI Dr. Reyes · 16 patients

Spitalul Judetean de Urgenta "Dr. Constantin Opris" Baia-Mare, Sectia Oncologie (Baia Mare, Romania)

ROU · PI Dr. Jansen · 2 patients

Stanford University (Stanford, CA)

USA · PI Dr. Nolan · 5 patients

State Health Centre Oncology Department (Budapest, Hungary)

HUN · PI Dr. Clarke · 30 patients

State Healthcare Institution "Republican Clinical Oncological Center of the Ministry of Health of Republic of Tatarstan" (Kazan', Russia)

RUS · PI Dr. Clarke · 12 patients

State Institution "Institute of Medical Radiology named after S.P.Grygoryev of National Academy of Medical Sciences of Ukraine" (Kharkiv, Ukraine)

UKR · PI Dr. Nolan · 3 patients

Tata Memorial Hospital, Department of Medical Oncology (Mumbai, India)

IND · PI Dr. Kim · 2 patients

The Crown Princess Mary Cancer Centre Westmead (Sydney, Australia)

AUS · PI Dr. Kowalski · 5 patients

University of Iowa (Iowa City, IA)

USA · PI Dr. Okafor · 5 patients

Vinnytsya Regional Clinical Oncologic Dispensary, Surgical Department (Vinnytsia, Ukraine)

UKR · PI Dr. Tanaka · 1 patients

confirm onsite visit

Site "Royal Perth Hospital (Perth, Australia)" is a statistical outlier among the 34 sites of "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" (risk score 0.496; visit-window compliance 50% vs study mean 88%, z=-2.92; missed-visit rate 12% vs study mean 3%, z=2.73). An on-site visit is proposed for 2026-10-13; the other sites stay on remote/centralized monitoring.

confirm onsite visit

Site "State Health Centre Oncology Department (Budapest, Hungary)" is a statistical outlier among the 34 sites of "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" (risk score 0.359; enrollment per open month 2.11 vs study mean 0.67, z=3.36). An on-site visit is proposed for 2026-10-13; the other sites stay on remote/centralized monitoring.

confirm onsite visit

Site "Lviv State Oncological Regional Treatment - Diagnostics Center, Chemotherapy Department (Lviv, Ukraine)" is a statistical outlier among the 34 sites of "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" (risk score 0.34; lab flags per patient 18.00 vs study mean 9.74, z=2.54). An on-site visit is proposed for 2026-10-13; the other sites stay on remote/centralized monitoring.

review aged queries

86 data queries are open past the 14-day SLA on "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" (86 past 30 days, 16 safety-critical P1). JSCDM benchmark: ≥80% reviewed within 2 weeks, target 95%. Oldest: [AE-006 · 5298 d] AE Anaemia (grade 4) for P2B-001 (onset 2012-03-28) is CTCAE grade 4 but not flagged serious. Confirm seriousn; [AE-006 · 5292 d] AE Neutropenia (grade 4) for P2B-003 (onset 2012-04-03) is CTCAE grade 4 but not flagged serious. Confirm seri; [VS-001 · 5230 d] Visit Cycle 2 Day 1: infusion (V3) for P2B-005 occurred on 2012-06-04, 5 d late against planned day 22 (2012-0; [VS-001 · 5210 d] Visit Cycle 3 Day 1: infusion; week-6 CT/MRI and ECHO/MUGA before dosing (V4) for P2B-005 occurred on 2012-06-; [VS-001 · 5208 d] Visit Cycle 5 Day 1: infusion; week-12 CT/MRI and ECHO/MUGA before dosing (V6) for P2B-003 occurred on 2012-06

assess serious event

OVERDUE SAE — SAE Narrative Subject P2B-132 (46-year-old male), enrolled in the Aldoxorubicin (INNO-206) 350 mg/m2 treatment arm, experienced a serious adverse event of Cholecystitis (System Organ Class: Hepatobiliary disorders), assessed as Grade 3 in severity. The event met the criterion of seriousness due to hospitalization. Onset occurred on 2013-09-29, with resolution on 2013-10-13, for a total duration of 14 days. The outcome was reported as RECOVERED/RESOLVED. The investigator's causality assessment was UNLIKELY (not suspected as related to study treatment). No dose adjustment was made as a result of this event (action taken with study treatment: DOSE NOT CHANGED). This event was classified as unexpected, as it is not listed on the doxorubicin hydrochloride label (doxorubicin class proxy). As an unexpected serious adverse event assessed as not related to study drug, expedited reporting was required within 15 days per ICH E2A guidelines, with a due date of 2013-10-14. This report is OVERDUE. Death within 30 days of the event: No. Additional Aggregate review over 608 events: potential new signal(s) not on the class label with ≥3 serious cases: Anaemia (9 patients, 9 serious events); Febrile neutropenia (16 patients, 16 serious events); Pyrexia (3 patients, 3 serious events); Cellulitis (3 patients, 3 serious events). FAERS class disproportionality flags (screening only): Anaemia PRR 4.8; Neutropenia PRR 11.37; Alopecia PRR 3.19; Febrile neutropenia PRR 36.86; Thrombocytopenia PRR 8.12; Pyrexia PRR 2.79. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

OVERDUE SAE — SAE Narrative – Subject P2B-130 Subject P2B-130 is a 51-year-old female enrolled in the study arm Aldoxorubicin (INNO-206) 350 mg/m2. The subject experienced a serious adverse event of Anaemia (Grade 3), System Organ Class: Blood and lymphatic system disorders, classified as serious due to hospitalization. Onset of the event occurred on 2013-10-17, with resolution documented on 2013-11-10, corresponding to a duration of 24 days. The outcome was reported as RECOVERED/RESOLVED. Following the onset of the event, the action taken with study treatment was DRUG INTERRUPTED. The investigator's assessment of causality was PROBABLE, and the event was categorized as suspected (related to study drug). The event was assessed as unexpected — not listed on the doxorubicin hydrochloride label (doxorubicin class proxy). Per ICH E2A expedited reporting requirements, this event triggered a 15-day reporting clock, with an expedited report due on 2013-11-01. This report is OVERDUE. Death within 30 days of the event: No. Additional source description: Grade 3 Aggregate review over 608 events: potential new signal(s) not on the class label with ≥3 serious cases: Anaemia (9 patients, 9 serious events); Febrile neutropenia (16 patients, 16 serious events); Pyrexia (3 patients, 3 serious events); Cellulitis (3 patients, 3 serious events). FAERS class disproportionality flags (screening only): Anaemia PRR 4.8; Neutropenia PRR 11.37; Alopecia PRR 3.19; Febrile neutropenia PRR 36.86; Thrombocytopenia PRR 8.12; Pyrexia PRR 2.79. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

OVERDUE SAE — SAE Narrative Subject P2B-134 is a 66-year-old female enrolled in the study arm Aldoxorubicin (INNO-206) 350 mg/m2. The subject experienced a serious adverse event of Anaemia (System Organ Class: Blood and lymphatic system disorders), Grade 3, classified as serious due to hospitalization. Onset of the event occurred on 2013-10-22. The event resolved on 2013-11-26, with an event duration of 35 days. The outcome was reported as RECOVERED/RESOLVED. As a result of the event, the following action was taken with study treatment: DOSE REDUCED. The investigator's assessment of causality was PROBABLE, and the event was categorized as suspected in relation to study treatment. Expectedness assessment: unexpected — not listed on the doxorubicin hydrochloride label (doxorubicin class proxy). Death within 30 days of the event: No. Regulatory reporting: This event met criteria for expedited reporting under a 15-day timeline (ICH E2A). The expedited report was due on 2013-11-06. Based on the information provided, this report is OVERDUE. Additional narrative detail from source Aggregate review over 608 events: potential new signal(s) not on the class label with ≥3 serious cases: Anaemia (9 patients, 9 serious events); Febrile neutropenia (16 patients, 16 serious events); Pyrexia (3 patients, 3 serious events); Cellulitis (3 patients, 3 serious events). FAERS class disproportionality flags (screening only): Anaemia PRR 4.8; Neutropenia PRR 11.37; Alopecia PRR 3.19; Febrile neutropenia PRR 36.86; Thrombocytopenia PRR 8.12; Pyrexia PRR 2.79. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

OVERDUE SAE — Serious Adverse Event Narrative Subject P2B-134 is a 66-year-old female enrolled in the study, assigned to the Aldoxorubicin (INNO-206) 350 mg/m2 treatment arm. The subject experienced a serious adverse event of Febrile neutropenia (System Organ Class: Blood and lymphatic system disorders), graded as Grade 4 in severity. The event met seriousness criteria on the basis of hospitalization. Onset of the event occurred on 2013-10-29, with resolution documented on 2013-11-04, for a total event duration of 6 days. The outcome was reported as RECOVERED/RESOLVED. In response to the event, study treatment action taken was DRUG INTERRUPTED. The investigator's assessment of causality was PROBABLE, and the event was categorized as suspected in relation to study treatment. The event was assessed as unexpected, as it is not listed on the doxorubicin hydrochloride label (used as a doxorubicin class proxy reference). Regulatory reporting: Per the applicable expedited reporting clock (15 days, consistent with ICH E2A for other serious unexpected suspected adverse reactions), the exp Aggregate review over 608 events: potential new signal(s) not on the class label with ≥3 serious cases: Anaemia (9 patients, 9 serious events); Febrile neutropenia (16 patients, 16 serious events); Pyrexia (3 patients, 3 serious events); Cellulitis (3 patients, 3 serious events). FAERS class disproportionality flags (screening only): Anaemia PRR 4.8; Neutropenia PRR 11.37; Alopecia PRR 3.19; Febrile neutropenia PRR 36.86; Thrombocytopenia PRR 8.12; Pyrexia PRR 2.79. [narrative drafted by claude-sonnet-5; verify against source fields]

assess serious event

OVERDUE SAE — Serious Adverse Event Narrative Subject P2B-129 is a 64-year-old female enrolled in the study arm receiving Doxorubicin 75 mg/m2. The subject experienced a serious adverse event of Anaemia (System Organ Class: Blood and lymphatic system disorders), Grade 3, classified as serious due to hospitalization. Onset occurred on 2013-10-30, with cycle 5 onset noted in the source description. The event resolved on 2013-12-02, resulting in an event duration of 33 days. As a result of the event, study treatment action taken was: drug interrupted. The event outcome was recorded as RECOVERED/RESOLVED. The investigator's causality assessment was PROBABLE, and the causality category was classified as suspected (related to study drug). The event was assessed as unexpected — not listed on the doxorubicin hydrochloride label (doxorubicin class proxy). Death within 30 days of the event: No. Regulatory Reporting Status: Per ICH E2A guidelines, this event met criteria for expedited reporting under the 15-day serious unexpected reaction timeline. The expedited report was due on 2013-11-14. This report is Aggregate review over 608 events: potential new signal(s) not on the class label with ≥3 serious cases: Anaemia (9 patients, 9 serious events); Febrile neutropenia (16 patients, 16 serious events); Pyrexia (3 patients, 3 serious events); Cellulitis (3 patients, 3 serious events). FAERS class disproportionality flags (screening only): Anaemia PRR 4.8; Neutropenia PRR 11.37; Alopecia PRR 3.19; Febrile neutropenia PRR 36.86; Thrombocytopenia PRR 8.12; Pyrexia PRR 2.79. [narrative drafted by claude-sonnet-5; verify against source fields]

validate tlf outputs

12 auto-generated TLF outputs (ICH E3 Section 14, batch 8b11fd774ddf26c5) for "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" await double-programming-equivalent validation.

approve csr draft

Clinical Study Report (draft) for "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" needs medical writing review and sign-off.

review tmf gaps

TMF for "A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Preliminary Efficacy and Safety of INNO-206 (Doxorubicin-EMCH) Compared to Doxorubicin in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcoma" is 60% complete against the DIA TMF Reference Model v3.2.1 (closeout stage); 10 auditable artifact(s) missing or incomplete — top gaps: 03.01.01 Regulatory Submission, 07.02.01 Expedited Safety Report, 02.03.01 Clinical Study Report. Confirm the filed TMF findings and assign owners.