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Trial record 25 of 125 for:    Recruiting, Not yet recruiting, Available Studies | "Osteosarcoma"

Trial of Sunitinib Plus Nivolumab After Standard Treatment in Advanced Soft Tissue and Bone Sarcomas (ImmunoSarc)

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ClinicalTrials.gov Identifier: NCT03277924
Recruitment Status : Recruiting
First Posted : September 11, 2017
Last Update Posted : September 11, 2017
Sponsor:
Information provided by (Responsible Party):
Grupo Espanol de Investigacion en Sarcomas

Brief Summary:

Phase I-II, single-arm, non-randomized, open-label, multicenter, international clinical trial, with two cohorts (Soft Tissue Sarcoma and Bone Sarcoma). Seven sites in Spain and 3 sites in Italy.

Patients will receive sunitinib 37.5 mg/day (or recommended dose defined in phase I) orally continuously + nivolumab 3 mg/kg intravenous every 2 weeks infused over 1 hour. Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.

The main goal is to evaluate the efficacy of the sunitinib plus nivolumab combination as measured by the progression-free survival rate (PFSR) at 6 months in patients with advanced soft tissue and bone sarcomas.


Condition or disease Intervention/treatment Phase
Soft Tissue Sarcoma Bone Sarcoma Drug: Sunitinib 37.5 MG [Sutent] Drug: Nivolumab 10 MG/ML [Opdivo] Phase 1 Phase 2

Detailed Description:

One arm survival design based on Lawless (Lawless, Statistical Models and Methods for Lifetime Data, John Wiley and Sons, 2003). Formulas are based on the assumptions of uniform accrual over time, no loss to follow-up, exponentially distributed death times.

For STS 2nd line cohort sample size has been obtained for the primary endpoint progression-free survival rate (PFSR) at 6 months. Estimated accrual time: 24 months. A PFSR of 5% will be considered not promising, whereas a response rate of 15% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 43 patients are needed in this cohort.

For bone sarcoma 2nd line cohort sample size has been obtained under the same assumptions than above, but with a type I error α of 0.10, therefore 32 patients are needed in this cohort.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Phase I-II, single-arm, non-randomized, open-label, multicenter, international clinical trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I-II Trial of Sunitinib Plus Nivolumab After Standard Treatment in Advanced Soft Tissue and Bone Sarcomas
Actual Study Start Date : May 31, 2017
Estimated Primary Completion Date : May 31, 2020
Estimated Study Completion Date : May 31, 2020


Arm Intervention/treatment
Experimental: Sunitinib+Nivolumab

Single arm of sunitinib 37.5 mg/day (or recommended dose defined in phase I) orally continuously + nivolumab 3 mg/kg intravenous every 2 weeks infused over 1 hour.

Sunitinib (Sutent): Hard Capsule (12.5, 25 mg). Oral use. Nivolumab (Opdivo) 10 mg/mL concentrate for solution for infusion. Intravenous use

Drug: Sunitinib 37.5 MG [Sutent]
Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.
Other Name: Sutent

Drug: Nivolumab 10 MG/ML [Opdivo]
Treatment will continue until disease progression, development of unacceptable toxicity, non-compliance, withdrawal of consent by the patient or investigator decision.
Other Name: Opdivo




Primary Outcome Measures :
  1. Progression-free survival rate (PFSR) [ Time Frame: 6 months ]
    Efficacy measured by the PFSR at 6 months according to RECIST 1.1. PFSR at 6 months is defined as the percentage of patients who did not experience progression or death due to any cause since the first dose of experimental treatment until month 6 after treatment initiation.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time between the date of first dose and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.

  2. Objective response rate (ORR) [ Time Frame: 2 months ]
    ORR is defined as the number of subjects with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) divided by the number of response evaluable subjects (according to RECIST 1.1 criteria).

  3. Immune response [ Time Frame: Up to 12 months ]
    To evaluate efficacy according to immune-related response.

  4. Tumor response [ Time Frame: 2 months ]
    To evaluate efficacy according to Choi response. The evaluation criteria will be based on the identification of target lesions in baseline and their follow-up until tumor progression.

  5. Safety profile: Adverse events [ Time Frame: Up to 12 months ]
    Safety profile of the experimental treatment, through assessment of adverse event type, incidence, severity, time of appearance, related causes, as well as physical explorations and laboratory tests. Toxicity will be graded and tabulated by using CTCAE 4.0.

  6. Clinical outcome [ Time Frame: At 36 months ]
    Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g. blood count, imaging tests, etc.) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
  2. Age: 18-80 years.
  3. Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangiosarcoma, solitary fibrous tumor and epithelioid sarcomas) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing sarcoma or dedifferentiated chondrosarcoma) confirmed by central pathology review. Mandatory paraffin embedded tumor blocks must be provided for all subjects without exception for biomarker analysis before treatment (first biopsy) and at end of month 3 or earlier (second biopsy).
  4. Metastatic/advanced disease in progression in the last 6 months.
  5. Patients have previously received at least anthracyclines.
  6. Measurable disease according to RECIST 1.1 criteria.
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
  8. Adequate hepatic, renal, cardiac, and hematologic function.
  9. Laboratory tests as follows:

    • Absolute neutrophil count ≥ 1,200/mm³
    • Platelet count ≥ 100,000/mm³
    • Bilirubin ≤ 1.5 mg/dL
    • PT and INR ≤ 1.5
    • AST and ALT ≤ 2.5 times upper limit of normal
    • Creatinine ≤ 1.5 mg/dL
    • Calcium ≤ 12 mg/dL
    • Blood glucose < 150 mg/dL
  10. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
  11. Females of childbearing potential must have a negative serum or urine pregnancy test within 24 hours prior to enrollment and agree to use birth control measures during study treatment and for 7 months after its completion. Patients must not be pregnant or nursing at study entry. Women/men of reproductive potential must have agreed to use an effective contraceptive method.

Exclusion Criteria:

  1. Three or more previous lines of chemotherapy for the advanced disease.
  2. Previous antiangiogenic agent, anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
  3. Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.).
  4. Active, known or suspected autoimmune disease.
  5. A condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 6. Uncontrolled intercurrent illness including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting within 24 weeks prior to registration, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI CTCAE version 4.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3).

7. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.

8. Other disease or illness within the past 6 months, including any of the following:

  • Myocardial infarction
  • Severe or unstable angina
  • Coronary or peripheral artery bypass graft
  • Symptomatic congestive heart failure
  • Cerebrovascular accident or transient ischemic attack
  • Pulmonary embolism 9. Evidence of a bleeding diathesis. 10. Ongoing cardiac dysrhythmias > Grade 2. 11. Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy.

    12. Psychiatric illness or social situation that would preclude study compliance.

    13. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.

    14. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.

    15. Hemorrhage ≥ Grade 3 in the past 4 weeks. 16. History of allergy to study drug components.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03277924


Contacts
Contact: Patricio Ledesma +34 971439900 ensayos@sofpromed.com

Locations
Italy
Istituto Ortopedico Rizzoli Not yet recruiting
Bologna, Italy, 40136
Contact: Stefano Ferrari         
Candiolo Cancer Institute - FPO, IRCCS Not yet recruiting
Candiolo, Italy, 10060
Contact: Giovanni Grignani         
Istituto Nazionale dei Tumori Not yet recruiting
Milano, Italy, 20133
Contact: Silvia Stacchiotti         
Spain
Hospital Universitari Vall d'Hebrón Not yet recruiting
Barcelona, Spain, 08035
Contact: Claudia Valverde         
Hospital de la Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08041
Contact: Antonio López Pousa         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain, 28041
Contact: José Antonio López Martín         
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Andrés Redondo         
Hospital Universitario Virgen del Rocío Recruiting
Sevilla, Spain, 41013
Contact: Javier Martín Broto         
Hospital Universitari i Politècnic La Fe Not yet recruiting
Valencia, Spain, 46026
Contact: Roberto Díaz de Beveridge         
Hospital Universitario Miguel Servet Recruiting
Zaragoza, Spain, 50009
Contact: Javier Martínez Trufero         
Sponsors and Collaborators
Grupo Espanol de Investigacion en Sarcomas
Investigators
Study Director: Javier Martín Broto Hospitales Universitarios Virgen del Rocío
Study Director: José Antonio López Martín Hospital Universitrario 12 de Octubre
Principal Investigator: Andrés Redondo Hospital Universitario La Paz
Principal Investigator: Claudia Valverde Hospital Universitari Vall d'Hebrón
Principal Investigator: Antonio López Pousa Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
Principal Investigator: Roberto Diaz de Beveridge Hospital Universitario La Fe
Principal Investigator: Javier Martínez Trufero Hospital Universitario Miguel Servet

Responsible Party: Grupo Espanol de Investigacion en Sarcomas
ClinicalTrials.gov Identifier: NCT03277924     History of Changes
Other Study ID Numbers: GEIS-52
First Posted: September 11, 2017    Key Record Dates
Last Update Posted: September 11, 2017
Last Verified: August 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Osteosarcoma
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Nivolumab
Sunitinib
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors