Phase I-II Evaluation of Sunitinib and Nivolumab with Chemotherapy in Advanced Soft Tissue and Bone Sarcomas
- Trial ID
- 2024-514776-40-00
- Protocol
- GEIS-52
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this clinical trial is to evaluate the efficacy and safety of the combination of **sunitinib** and **nivolumab** in patients with advanced soft tissue and bone sarcomas. This is assessed by determining the recommended dose for Phase II and measuring the progression-free survival rate (PFSR) at 6 months in Stage 1, Phase 2, and at 6 or 12 months in Stage 2, Phase 2, depending on the cohort. Additionally, the trial aims to determine the maximum tolerated dose (MTD) of various drug combinations in different cohorts, which is crucial for optimizing treatment regimens and improving patient outcomes.
Secondary objectives include:
- Evaluating the safety profile according to CTCAE 4.0 and 5.0.
- Assessing efficacy through progression-free survival rate (PFSR) at 6 and 12 months, overall survival (OS), and overall response rate (ORR).
- Contributing to translational studies and evaluating the outcome of post-protocol treatments.
- Determining the correlation between efficacy and potential predictive biomarkers, as well as prognostic and response correlation with specific hematological indicators.
Participants
The clinical trial involves a total of **four participants** diagnosed with **advanced soft tissue and bone sarcomas**. The study population includes both male and female subjects, with an age range of 12 to 80 years. Participants were selected based on their diagnosis and progression of the disease, as well as their ability to provide informed consent and comply with study procedures. The trial includes individuals with a **measurable disease** according to RECIST 1.1 criteria and an **Eastern Cooperative Oncology Group (ECOG) Performance Status** of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must have adequate hepatic, renal, cardiac, and hematologic function. The trial also considers lifestyle factors such as the requirement for effective contraceptive measures for participants of reproductive potential. The study population is characterized by a vulnerable group, given the nature of the disease and the inclusion of younger participants. The sponsor has not provided additional information regarding specific lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of a combination therapy involving **sunitinib** and **nivolumab** in patients with advanced soft tissue and bone sarcomas. This is a Phase I-II trial, structured as a randomized, double-blind, controlled study. The trial is expected to run from February 2017 to May 2025, with the primary objective of determining the recommended dose and assessing the progression-free survival rate (PFSR) at 6 and 12 months, depending on the cohort.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as measurable disease according to RECIST 1.1 criteria, adequate organ function, and an ECOG Performance Status of 0-1. The trial includes multiple cohorts, each with specific objectives, such as determining the maximum tolerated dose (MTD) of various drug combinations. Follow-up visits will be scheduled to monitor safety, efficacy, and any adverse events, with assessments conducted according to CTCAE guidelines. The end-of-study visit will evaluate overall survival, response rates, and contribution to translational studies through biological sample collection.
Participant involvement is expected to last until the end of the trial or until progression or unacceptable toxicity occurs. Conditions that may lead to early termination from the study include non-compliance with the protocol, withdrawal of consent, or adverse events that compromise participant safety. The trial aims to provide comprehensive data on the safety and efficacy of the treatment regimen, contributing valuable insights into the management of advanced sarcomas.
Treatment
The clinical trial involves the administration of **Sunitinib**, marketed under the name Sutent, which is provided in two different dosages: 12.5 mg and 25 mg hard capsules. The pharmaceutical form is a hard capsule, and the route of administration is oral. Sunitinib is a chemical substance with the active ingredient identified as N-(2-(diethylamino)ethyl)-5-((Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide. The medication is produced by Pfizer Europe MA EEIG and is classified under the ATC code L01EX01. The administration schedule and dosage frequency are determined based on the trial phase and cohort specifics, with compliance monitored through standard clinical trial procedures.
**Nivolumab**, marketed as OPDIVO, is another experimental medication used in this trial. It is provided as a 10 mg/mL concentrate for solution for infusion. The pharmaceutical form is a solution for infusion, and the route of administration is intravenous. Nivolumab is a protein-based substance, specifically classified as a protein - other, with the active ingredient known as BMS936558. This medication is produced by Bristol-Myers Squibb Pharma EEIG and is classified under the ATC code L01FF01. The dosing schedule and frequency are tailored to the trial's specific objectives and phases, with participant compliance monitored accordingly.
In addition to the experimental medications, the trial may involve the use of standard-of-care therapies or comparator treatments as deemed necessary by the study protocol. The trial's primary objectives include determining the recommended dose and evaluating the efficacy of the sunitinib and nivolumab combination in patients with advanced soft tissue and bone sarcomas. Compliance with the dosing regimen is monitored through established clinical trial methodologies to ensure accurate assessment of the treatment's efficacy and safety.
Efficacy
The efficacy of the clinical trial involving the combination of **sunitinib** and **nivolumab** in patients with advanced soft tissue and bone sarcomas will be assessed primarily through the measurement of the **progression-free survival rate (PFSR)**. In Phase 2 of Stage 1, the PFSR at 6 months will be evaluated, defined as the percentage of patients who do not experience progression or death due to any cause from enrollment until six months post-enrollment. For Stage 2, Cohorts 1-6, the PFSR will also be measured at 6 months, while for the ASPS cohort, it will be assessed at 12 months. The PFSR at 12 months is similarly defined as the percentage of patients who do not experience progression or death from the date of enrollment until twelve months post-enrollment.
Secondary efficacy endpoints include overall survival (OS), defined as the time from enrollment to death from any cause, and overall response rate (ORR), which is the number of subjects with a best overall response of complete or partial response divided by the number of response-evaluable subjects, according to RECIST 1.1 criteria. Additionally, the trial will assess the safety profile of the experimental treatment by evaluating adverse event types, incidence, severity, and related causes, with toxicity graded using CTCAE 4.0 or 5.0, depending on the phase and cohort. The trial will also explore the correlation between efficacy and potential predictive biomarkers, as well as prognostic and response correlations with specific hematological parameters.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Stage 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.
- Stage 1. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
- Stage 2. Cohorts 1-6. 1. Patients (or legal tutors) 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.
- Stage 2. Cohorts 1-6. 2. Age: 12-80 years.
- Stage 2. Cohorts 1-6. 3. Diagnosis of dedifferentiated chondrosarcoma, extraskeletal myxoid chondrosarcoma, vascular sarcomas (including angiosarcoma, hemangioendothelioma and intimal sarcomas), solitary fibrous tumor (excluding dedifferentiated SFT), alveolar soft part sarcoma, and clear cell sarcoma confirmed by central pathology review.
- Stage 2. Cohorts 1-6. 4. Mandatory paraffin embedded tumor blocks must be provided for all subjects without exception for biomarker analysis before treatment.
- Stage 2. Cohorts 1-6. 5. Metastatic/locally advanced unresectable disease in progression in the last 6 months according to RECIST 1.1. Patients with recent diagnosis of metastatic disease can be eligible (if they are not candidates to anthracycline-based treatment).
- Stage 2. Cohorts 1-6. 6. Patients should have previously received at least anthracyclines. Patients in the cohorts of subtypes sensitive to antiangiogenic therapy (SFT, ASPS, CCS, EMC or DDCS) are eligible even if not previously treated.
- Stage 2. Cohorts 1-6. 7. Previous therapy with antiangiogenics is allowed.
- Stage 2. Cohorts 1-6. 8. Measurable disease according to RECIST 1.1 criteria.
- Stage 2. Cohorts 1-6. 9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Stage 1. 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.
- Stage 2. Cohorts 1-6. 10. Adequate hepatic, renal, cardiac, and hematologic function.
- Stage 2. Cohorts 1-6. 11. 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 in the absence of anticoagulant therapy • AST and ALT ≤ 2.5 times upper limit of normal • Creatinine ≤ 1.5 mg/dL (or Cr clearance ≥ 60 ml/min) • Calcium ≤ 12 mg/dL
- Stage 2. Cohorts 1-6. 12. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan.
- Stage 2. Cohorts 1-6. 13. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment and agree to use birth control measures during study treatment and for 6 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.
- Stage 2. Cohort 7. 1. The patient or his/her legal tutors must provide written informed consent prior to performance of 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. study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of
- Stage 2. Cohort 7. 2. Age: 18-80 years.
- Stage 2. Cohort 7. 3. Diagnosis of advanced/metastatic undifferentiated pleomorphic sarcoma (UPS) (cohort 7a) or leiomyosarcoma (LMS) (cohort 7b) confirmed by central pathology review.
- Stage 2. Cohort 7. 4. Mandatory pre-treatment formalin-fixed paraffin embedded (FFPE) tumor tissue must be provided for all subjects without exception for central pathology review and the translational study. Archive tissue can be used for diagnosis confirmation but a recent biopsy (<3 months) is mandatory for translational research. If it is not available or is older than 3 months, the patient must be willing to have a pre-treatment re-biopsy of primary or metastatic tumor (baseline biopsy) within 28 days prior to enrollment.
- stage 2. Cohort 7. 5. Measurable disease according to RECIST v1.1 criteria.
- Stage 2. Cohort 7. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Stage 1. Age: 18-80 years.
- Stage 2. Cohort 7. 7. The patient must be naïve of any previous treatment with anthracyclines (not even in adjuvant chemotherapy).
- stage 2. Cohort 7. 8. Adequate organ, hepatic, renal, cardiac, and hematologic function.
- Stage 2. Cohort 7. 9. Laboratory tests as follows: • Absolute neutrophil count ≥ 1,500/mm³ • Platelet count ≥ 100,000/mm³ • Hg > 9 g/dL • 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 or estimated creatinine clearance ≥ 60 mL/min • Blood glucose < 150 mg/dL
- Stage 2. Cohort 7. 10. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan assessed within 28 days before enrollment.
- Stage 2. Cohort 7. 11. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Patients must not be pregnant or nursing at study entry.
- Stage 2. Cohort 7. 12. Women and men of reproductive potential must have agreed to use an effective contraceptive method during study treatment and for 6 months after the last dose of study drug.
- Stage 1. Histologic diagnosis of soft tissue sarcoma (undifferentiated pleomorphic sarcoma, synovial sarcoma, alveolar soft part sarcoma, clear cell sarcoma, angiosarcoma, epithelioid hemangioendothelioma, solitary fibrous tumor,epithelioid sarcoma and extraskeletal myxoid chondrosarcoma) or bone sarcoma (osteosarcoma/high grade bone sarcoma, Ewing’s sarcoma, chondrosarcoma and 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).
- Stage 1. Metastatic/advanced disease in progression in the last 6 months.
- Stage 1. Measurable disease according to RECIST 1.1 criteria.
- Stage 1. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Stage 1. Adequate hepatic, renal, cardiac, and hematologic function.
- Stage 1. 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
- Stage 2. Cohort 8. 1. The patient or his/her legal tutors 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 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.
- Stage 2. Cohort 8. 2. Age: 12-40 years.
- Satge 2. Cohort 8. 3. Diagnosis of resectable primary metastatic high-grade osteosarcoma confirmed by central pathology review. Resection of primary tumor +/- metastatic disease has to be feasible and planned.
- Stage 2. Cohort 8. 4. Mandatory pre-treatment formalin-fixed paraffin embedded (FFPE) tumor tissue must be provided for all subjects without exception for central pathology review and the translational study. The patient must be willing to have a pre-treatment re-biopsy of primary or metastatic tumor (baseline biopsy) within 28 days prior to enrollment if diagnosis biopsy does not have enough remaining tissue for translational purposes.
- Stage 2. Cohort 8. 5. Measurable disease according to RECIST v1.1 criteria.
- Stage 2. Cohort 8. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
- Stage 2. Cohort 8. 7. The patient must be naïve of any previous treatment.
- Stage 2. Cohort 8. 8. Adequate organ, hepatic, renal, cardiac, and hematologic function.
- Stage 2. Cohort 8. 9. Laboratory tests as follows: • Absolute neutrophil count ≥ 1,500/mm³ • Platelet count ≥ 100,000/mm³ • Hg > 9 g/dL • 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 or estimated creatinine clearance ≥ 60 mL/min • Blood glucose < 150 mg/dL
- Stage 2. Cohort 8. 10. Left ventricular ejection fraction ≥ 50% by echocardiogram or MUGA scan assessed within 28 days before enrollment.
- Stage 2. Cohort 8. 11. Females of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to enrollment. Patients must not be pregnant or nursing at study entry.
- Stage 2. Cohort 8. 12. Women and men of reproductive potential must have agreed to use an effective contraceptive method during study treatment and for 6 months after the last dose of study drug.
Exclusion Criteria
- Stage 1. 1. Four or more previous lines of chemotherapy for the advanced disease.
- Satge 1. 2. Previous anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
- Stage 1. 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.).
- Stage 1. 4. Active, known or suspected autoimmune disease.
- Stage 1. 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.
- Stage 1. 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).
- Stage 1. 7. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
- Stage 1. 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
- Stage 1. 9. Evidence of a bleeding diathesis.
- Stage 1. 10. Ongoing cardiac dysrhythmias > Grade 2.
- Stage 1. 11. Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy.
- Stage 1. 12. Psychiatric illness or social situation that would preclude study compliance.
- Stage 1. 13. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
- Stage 1. 14. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
- Stage 1. 15. Hemorrhage ≥ Grade 3 in the past 4 weeks.
- Stage 1. 16. History of allergy to study drug components.
- Stage 1. 17. Previous anticoagulants due to thrombotic events.
- Stage 1. 18. History of another cancer with the exception of adequately treated basal cell carcinoma or cervical cancer in situ.
- Stage 1. 19. Presence of brain or central nervous system metastases.
- Stage 2. Cohorts 1-6. 1. Four or more previous lines of chemotherapy.
- Stage 2. Cohorts 1-6. 2. Previous anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
- Stage 2. Cohorts 1-6. 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.).
- Stage 2. Cohorts 1-6. 4. Active, known or suspected autoimmune disease.
- Stage 2. Cohorts 1-6. 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.
- Stage 2. Cohorts 1-6. 6. Uncontrolled intercurrent illness (or within 12 months prior to first dose of study drug) including (not limited to): symptomatic congestive heart failure (CHF) (New York Heart Association [NYHA] III/IV), unstable angina pectoris or coronary angioplasty, or stenting, unstable cardiac arrhythmia (ongoing cardiac dysrhythmias of NCI-CTCAE] version 5.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3).
- Stage 2. Cohorts 1-6. 7. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection.
- Stage 2. Cohorts 1-6. 8. Other disease or illness within the past 12 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
- Stage 2. Cohorts 1-6. 9. Evidence of a bleeding diathesis.
- Stage 2. Cohorts 1-6. 10. Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy.
- Stage 2. Cohorts 1-6. 11. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
- Stage 2. Cohorts 1-6. 12. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
- Stage 2. Cohorts 1-6. 13. Hemorrhage ≥ Grade 3 in the past 4 weeks.
- Stage 2. Cohorts 1-6. 14. History of allergy to study drug components.
- Stage 2. Cohorts 1-6. 15. Anticoagulants due to thrombotic events, with the exception of deep venous thrombosis in limbs, with a stable dose of low-weigh heparine and in the absence of secondary hemorrages.
- Stage 2. Cohorts 1-6. 16. History of another cancer in the previous 5 years with the exception of adequately treated squamous or basal cell carcinoma of the skin or cervical cancer in situ.
- Stage 2. Cohorts 1-6. 17. Presence of brain or central nervous system metastases, unless they are controlled (completely resected or irradiated and/or asympthomatic, no need of steroids).
- Stage 2. Cohorts 1-6. 18. Unwilling to participate in the translational study (not providing mandatory biopsies at baseline).
- Stage 2. Cohorts 1-6. 19. Live vaccine 30 days or fewer prior to enrollment.
- Stage 2. Cohort 7. 1. Diagnosis of any sarcoma different from undifferentiated pleomorphic sarcoma and leiomyosarcoma.
- Stage 2. Cohort 7. 2. Previous treatment with anthracyclines or any other systemic therapy for advanced sarcoma. The exception is hormone therapy or previous systemic therapy for a previous neoplasm (see exclusion criteria number 13), if this is controlled as long as previous therapy did not include anthracyclines. Adjuvant therapy not containing anthracyclines (eg: gemcitabine-docetaxel) is allowed.
- Stage 2. Cohort 7. 3. Previous anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
- Stage 2. Cohort 7. 4. Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.).
- Stage 2. Cohort 7. 5. Active, known or suspected autoimmune disease.
- Stage 2. Cohort 7. 6. 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.
- Stage 2. Cohort 7. 7. 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 5.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3).
- Stage 2. Cohort 7. 8. HBV and HCV serologies must be preformed prior to inclusion. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection is not allowed.
- Stage 2. Cohort 7. 9. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
- Stage 2. Cohort 7. 10. Any of the following diseases/illnesses within the previous 6 months: • Myocardial infarction • Severe or unstable angina • Coronary or peripheral artery bypass graft • Symptomatic congestive heart failure • Cerebrovascular accident or transient ischemic attack (TIA) • Pulmonary embolism • Evidence of a bleeding diathesis. • Ongoing cardiac dysrhythmias > Grade 2.
- Stage 2. Cohort 7. 11. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
- Stage 2. Cohort 7. 12. History of allergy to study drug components.
- Stage 2. Cohort 7. 13. History of another cancer with the exception of adequately treated basal cell carcinoma or in situ cervical cancer, or with a relapse-free interval longer than 3 years after treatment of the primary cancer with no substantial risk of recurrence.
- Stage 2. Cohort 7. 14. Presence of brain or central nervous system metastases at the time of enrollment, unless they are controlled (completely resected or irradiated and/or asympthomatic, no need of steroids).
- Stage 2. Cohort 7. 15. Patient is unwilling to provide mandatory translational tumor samples or biopsies (if required) cannot be easily traken.
- Stage 2. Cohort 8. 1. Diagnosis of parosteal, periosteal osteosarcoma or any other bone sarcoma.
- Stage 2. Cohort 8. 2. Previous systemic therapy.
- Stage 2. Cohort 8. 3. Previous anti-programmed death-1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti PD-L2 or anti CTLA-4 antibody.
- Stage 2. Cohort 8. 4. Prior immune-related adverse event (Grade 3 or higher immune-related pneumonitis, hepatitis, colitis, endocrinopathy) with prior immunotherapy (e.g. cancer vaccine, cytokine, etc.).
- Stage 2. Cohort 8. 5. Active, known or suspected autoimmune disease.
- Stage 2 . Cohort 8. 6. 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.
- Stage 2. Cohort 8. 7. 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 5.0 Grade >= 2), known psychiatric illness that would limit study compliance, intra-cardiac defibrillators, known cardiac metastases, or abnormal cardiac valve morphology (>= Grade 3).
- Stage 2. Cohort 8. 8. HBV and HCV serologies must be performed prior to inclusion. Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection is not allowed.
- Stage 2. Cohort 8. 9. Pre-existing thyroid abnormality, defined as abnormal thyroid function tests despite medication.
- Stage 2. Cohort 8. 10. Any of the following diseases/illnesses within the previous 6 months: • Myocardial infarction • Severe or unstable angina • Coronary or peripheral artery bypass graft • Symptomatic congestive heart failure • Cerebrovascular accident or transient ischemic attack (TIA) • Pulmonary embolism • Evidence of a bleeding diathesis • Ongoing cardiac dysrhythmias > Grade 2.
- Stage 2. Cohort 8. 11. Prolonged QTc interval (i.e., QTc > 450 msec for males or QTc > 470 msec for females) on baseline ECG.
- Stage 2. Cohort 8. 12. History of allergy to study drug components.
- Stage 2. Cohort 8. 13. History of another cancer with the exception of adequately treated basal cell carcinoma or in situ cervical cancer, or with a relapse-free interval longer than 3 years after treatment of the primary cancer with no substantial risk of recurrence.
- Stage 2. Cohort 8. 14. Presence of brain or central nervous system metastases at the time of enrollment, unless they are controlled (completely resected or irradiated and/or asympthomatic, no need of steroids).
- Stage 2. Cohort 8. 15. Patient is unwilling to provide mandatory translational tumor samples or biopsies (if required) cannot be easily taken.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Italy | Not Recruiting | 01 Feb 2017 | 40 |
 Spain | Not Recruiting | 01 Feb 2017 | 145 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Sutent 12.5 mg hard capsules | Test | HARD CAPSULES | ORAL | — | — | PRD3432966 |
Sutent 25 mg hard capsules | Test | HARD CAPSULES | ORAL USE | — | — | PRD3432965 |
OPDIVO 10 mg/mL concentrate for solution for infusion. | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS USE | — | — | PRD2941372 |