Preliminary Efficacy and Safety of INNO-206 Compared to Doxorubicin in Advanced Soft Tissue Sarcoma

NCT ID: NCT01514188

Last Updated: 2024-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-11
• Study Completion Date: 2014-12-15

Brief Summary

This is a phase 2b, randomized, open-label, prospective, multicenter study comparing treatment with INNO 206 to doxorubicin in subjects with metastatic, locally advanced, or unresectable soft tissue sarcomas who have not been previously treated with any chemotherapy except potentially as adjuvant or neoadjuvant chemotherapy, and no evidence of tumor recurrence has occurred for at least 12 months.

Detailed Description

One hundred five subjects will be enrolled and randomized 2:1 to receive either INNO-206 or doxorubicin. INNO-206 at a dosage of 350 mg/m2 (doxorubicin equivalents of 260 mg/m2) will be administered as a 30 minute IVI on Day 1 of each cycle to approximately 70 subjects. Doxorubicin (75 mg/m2) will be administered to approximately 35 subjects on Day 1 of each cycle. An individual cycle of therapy will be defined as a 3-week (21-day) period. Cycles will be repeated every 3 weeks. Multiple cycles may be administered until the subject is withdrawn from therapy or until a maximum of 6 cycles are administered. Overall response rates as well as individual categories of response (CR, PR, SD, and PD) will be determined using RECIST 1.1.[28] Time-to-event endpoints, including PFS and OS will be assessed using the Kaplan Meier method.[30] Evaluation of 4- and 6-month progression-free survival will also be performed. Toxicity (adverse events) will be recorded using the NCI CTCAE, version 4.0 (published 28 May 2009).

Conditions

Metastatic Soft Tissue Sarcoma; Locally Advanced Soft Tissue Sarcoma; Unresectable Soft Tissue Sarcoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Doxorubicin

Group Type: ACTIVE_COMPARATOR

Doxorubicin

Intervention Type: DRUG

Doxorubicin administered at 75 mg/m2 for up to 6 consecutive cycles.

INNO-206

Group Type: EXPERIMENTAL

INNO-206

Intervention Type: DRUG

INNO-206 administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously (IV) on Day 1 every 21 days for up to 6 consecutive cycles

Interventions

INNO-206

INNO-206 administered at 350 mg/m2 (260 mg/m2 doxorubicin equivalent) intravenously (IV) on Day 1 every 21 days for up to 6 consecutive cycles

Intervention Type: DRUG

Doxorubicin

Doxorubicin administered at 75 mg/m2 for up to 6 consecutive cycles.

Intervention Type: DRUG

Other Intervention Names

DOXO-EMCH

Eligibility Criteria

Inclusion Criteria

• Age between 15-80 years (US only), and 18-80 (rest of world (ROW)), male or female.
• Adjuvant or neoadjuvant chemotherapy (including doxorubicin) allowed if no tumor recurrence for at least 12 months since the last measurement, beginning or end of last chemotherapy.
• Histologically or cytologically confirmed, locally advanced, unresectable, and/or metastatic soft tissue sarcoma of intermediate or high grade.
• Capable of providing informed consent and complying with trial procedures.
• ECOG performance status 0-2.
• Life expectancy > 12 weeks.
• Measurable tumor lesions according to RECIST 1.1 criteria.
• Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)
• Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.
• Geographic accessibility to the site that ensures the subject will be able to keep all study-related appointments.

Exclusion Criteria

• Prior chemotherapy unless for adjuvant or neoadjuvant therapy with no tumor recurrence for at least 12 months.
• Prior exposure to > 3 cycles or 225 mg/m2 of doxorubicin or Doxil®.
• Palliative surgery and/or radiation treatment less than 4 weeks prior to Randomization.
• Exposure to any investigational agent within 30 days of Randomization.
• Current Stage 1 or 2 soft tissue sarcomas.
• Current evidence/diagnosis of alveolar soft part sarcoma, chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma, Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, clear cell sarcomas and unresectable low grade liposarcomas.
• Central nervous system metastasis
• History of other malignancies except cured basal cell carcinoma, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for > 5 years.
• Laboratory values: Screening serum creatinine > 1.5x upper limit of normal (ULN), alanine aminotransferase (ALT) > 3 × ULN or >5 × ULN if liver metastases are present, total bilirubin > 3 × ULN, absolute neutrophil count < 1,500/mm3, platelet concentration < 100,000/mm3, hematocrit level < 25% for females or < 27% for males, or coagulation tests (prothrombin time [PT], partial thromboplastin time [PTT], International Normalized Ratio [INR]) > 1.5 × ULN, albumin < 2.0 g/dL.
• Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines.
• Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V.
• Baseline QTc > 470 msec and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed.
• History or signs of active coronary artery disease with or without angina pectoris.
• Serious myocardial dysfunction defined as scintigraphically (e.g. MUGA, myocardial scintigram) or ultrasound determined absolute left ventricular ejection fraction (LVEF) < 45% of predicted.
• History of HIV infection.
• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.
• Major surgery within 3 weeks prior to Randomization.
• Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.
• Any condition that is unstable and could jeopardize the subject's participation in the study.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ImmunityBio, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sant Chawla, M.D.

Role: PRINCIPAL_INVESTIGATOR

Sarcoma Oncology Center

Daniel Levitt, M.D., Ph.D.

Role: STUDY_DIRECTOR

CytRx

Locations

Sarcoma Oncology Center

Santa Monica, California, United States

Stanford University

Stanford, California, United States

University of Iowa

Iowa City, Iowa, United States

Pennsylvania Hematology Oncology Associates

Philadelphia, Pennsylvania, United States

CTRC Institute for Drug Development, University of Texas

San Antonio, Texas, United States

Royal North Shore

St Leonards, New South Wales, Australia

Epworth HealthCare Clinical Trials and Research Centre

Richmond, Victoria, Australia

Border Medical Oncology

Wodonga, Victoria, Australia

Royal Hobart Hospital

Hobart, , Australia

Royal Perth Hospital

Perth, , Australia

Mount Medical Centre

Perth, , Australia

The Crown Princess Mary Cancer Centre Westmead

Sydney, , Australia

State Health Centre Oncology Department

Budapest, , Hungary

Hemato Oncology Clinic, Vedanta Institute of Medical Science

Thaltej, Ahmedaba, India

Hemato Oncology Clinic, Vedanta Institute of Medical Science

Ahmedabad, Gujarat, India

M.S. Ramaiah Medical College and Hospitals

Bangalore, Karnataka, India

Curie Manavata Cancer Centre

Nashik, Maharashtra, India

Delhi State Cancer Institute

Pune, Maharashtra, India

Jehangir Clinical Development Centre Pvt Ltd

Pune, Maharashtra, India

Delhi State Cancer Institute

Mandoli, National Capital Territory of Delhi, India

Noble Hospital Clinical Research Department 1st Floor

Hadapsar, Pune Maharashtra, India

Christian Medical College

Vellore, Tami Nadu, India

Tata Memorial Hospital, Department of Medical Oncology

Mumbai, , India

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

Cluj-Napoca, County Cluj, Romania

Clinical County Hospital Mures, Medical Oncology Department

Târgu Mureş, County Mures, Romania

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

Baia Mare, Judet Maramures, Romania

Medisprof SRL

Cluj-Napoca, , Romania

State Healthcare Institution "Republican Clinical Oncological Center of the Ministry of Health of Republic of Tatarstan"

Kazan', Tatarstan Republic, Russia

Blokhin Cancer Research Center

Moscow, , Russia

Municipal institution "Chernivtsi Regional Clinical Oncologic Dispensary",

Chernivtsi, , Ukraine

Municipal Institution "Dnipropetrovsk City Multi-Field Clinical Hospital #4" of Dnipropetrovsk Regional Councel

Dnipropetrovsk, , Ukraine

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

Kharkiv, , Ukraine

Lviv State Oncological Regional Treatment - Diagnostics Center, Chemotherapy Department

Lviv, , Ukraine

Vinnytsya Regional Clinical Oncologic Dispensary, Surgical Department

Vinnytsia, , Ukraine

Countries

United States; Australia; Hungary; India; Romania; Russia; Ukraine

References

Chawla SP, Papai Z, Mukhametshina G, Sankhala K, Vasylyev L, Fedenko A, Khamly K, Ganjoo K, Nagarkar R, Wieland S, Levitt DJ. First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial. JAMA Oncol. 2015 Dec;1(9):1272-80. doi: 10.1001/jamaoncol.2015.3101.

Reference Type: DERIVED

PMID: 26378637 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://pubmed.ncbi.nlm.nih.gov/26378637/

Related Info

https://pubmed.ncbi.nlm.nih.gov/25312684/

Related Info

Other Identifiers

INNO-206-P2-STS-01

Identifier Type: -

Identifier Source: org_study_id