Trial of Sunitinib and/or Nivolumab Plus Chemotherapy in Advanced Soft Tissue and Bone Sarcomas
- Conditions
- Soft Tissue SarcomaBone Sarcoma
- Interventions
- Registration Number
- NCT03277924
- Lead Sponsor
- Grupo Espanol de Investigacion en Sarcomas
- Brief Summary
Phase I-II, single-arm, non-randomized, open-label, multicenter, international clinical trial, with two stages. Stage one has two cohorts (soft tissue sarcoma and bone sarcoma) and stage two has eight cohorts (DDCS, EMC, VS, SFT, CCS, ASPS, UPS, LMS and OS). Nine sites in Spain, 3 sites in Italy and 1 site in the United Kingdom.
Stage 1 (PHASE 1 and PHASE 2)
Objective: To determine the recommended dose of the sunitinib plus nivolumab combination for phase II part. 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.
Treatment: Adult patients will receive an initial induction phase (IP) from day 1 to day 14 of sunitinib 37.5 mg/day followed by a maintenance phase (MP) of sunitinib 37.5 mg/day continuously + nivolumab 3 mg/kg intravenous every 2 weeks infused over 1 hour. If three or more DLTs occur from day 15 to 42, for an initial set of 10 patients, sunitinib dose will be lowered to 25 mg/day or treatment schedule will be changed to 2 weeks on and one week off until recovery from toxicities.
Stage 2
C1 to 6
Objective: To evaluate the efficacy of the sunitinib plus nivolumab combination as measured by PFSR at 6 months (CS/DDCS, EMC, VS, SFT, CCS cohorts) and at 12 months (ASPS cohort).
Treatment: Adult patients will receive an initial induction phase (IP) from day 1 to day 14 of sunitinib 37.5 mg/day followed by a maintenance phase (MP) of sunitinib 25mg/day continuously + nivolumab 240mg every 2 weeks. Pediatric patients will receive an initial IP from day 1 to day 14 of (\<18 years) sunitinib at 25 mg/day unless the body surface area (BSA) of the patient is \>1.7. If BSA is \>1.7, then sunitinib 37.5 mg/day will be given followed by a MP of sunitinib 25 mg/day continuously + nivolumab 240 mg every 2 weeks regimen (if weight ≥40 kg) or sunitinib 25 mg/day continuously + nivolumab 3 mg/kg every 2 weeks regimen (if weight \<40kg).
C 7
Objective: To determine the MTD of the epirubicin + ifosfamide + nivolumab combination in undifferentiated pleomorphic sarcoma and of the doxorubicin + dacarbazine + nivolumab combination in leiomyosarcoma.
Treatment:Cohort 7a dose level 0: Patients will receive epirubicin dose of 60 mg/m2/d, d1 and d2 IV 20 minutes; followed by ifosfamide 3 g/m2/d d1-3, IV 3h with MESNA protection (40% of total dose of ifosfamide in each administration at 0, 3 and 6 h from ifosfamide initiation). Once finished Ifosfamide infusion of day 3, nivolumab is administered during 30 minutes, at dose of 360 mg IV, Q3W. GCSF support is mandatory. If three or more DLTs occur nivolumab dose will be lowered to dose level -1.
Cohort 7b dose level 0: Patients will receive doxorubicin at dose of 75 mg/m2/d, d1 IV 20 minutes; followed by dacarbazine 400 mg//m2/d IV 60 minutes. Dacarbazine is administered also on day 2 of cycle. Once finished Dacarbazine infusion of day 2, nivolumab is administered for 30 minutes, at dose of 360 mg IV, Q3W. GCSF support is mandatory. If three or more DLTs occur nivolumab dose will be lowered to dose level -1 where patients will receive doxorubicin at dose of 75 mg/m2/d, d1 IV 20 minutes; followed by dacarbazine 400 mg//m2/d IV 60 minutes. Dacarbazine is administered also on day 2 of cycle. Once finished dacarbazine infusion of day 2, nivolumab is administered for 30 minutes, at dose of 240 mg IV, Q3W. GCSF support is mandatory. One-year maintenance of nivolumab is foreseen in the absence of progressive disease.
C 8
Objectives:To determine the MTD of the MAP + nivolumab combination (phase I). Proportion of patients achieving good pathological response (phase II)
Treatment dose level 0: In the IP, patients will receive CDDP 120 mg/m2 in 48h IV infusion (days 1-2) followed by doxorubicin 75 mg/m2 in 48h IV infusion (days 3-4). CDDP and doxorubicin will be given on days 1-4 and 36-39. Nivolumab administration will start on day 4 at flat dose 240 mg (after the end of doxorubicin), being the following doses administered on days 18, 39, and 53 (240 mg). HD methotrexate at 12 g/m2 in 2-h infusion will be administered on days 22, 29, 57, and 64. Surgery will be performed after finishing IP. Adjuvant chemotherapy will be administered after surgery. During the MP patients will receive nivolumab on day 210, every two weeks up to day 364. If three or more DLTs occur, then nivolumab dose level -1 will be activated.
- Detailed Description
Stage 1
Sample size has been obtained for a one-arm one-stage survival design based on Brookmeyer-Crowley like test. The test statistic for survival probability is assumed to be based on the non-parametric estimate of the survival distribution. 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 PFSRof 15% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.80, 48 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 38 patients are needed in this cohort.
Stage 2
Cohorts 1-6:
COHORT 1 - Dedifferentiated Chondrosarcoma (DDCS): For DDCS sample size is obtained for the primary endpoint of 6-month progression-free survival rate, estimated accrual 24 months. A 6-m PFSR of 40% will be considered not promising whereas of 70% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 23 patients were estimated in this cohort. With one arm survival design based on survival probability a Brookmeyer-Crowley like test is assumed (Brookmeyer, 1982) \[65\]. If at least 14 cases over the 23 patients have a 6-m PFSR, then further investigation of the experimental treatment is warranted.
COHORT 2 - Extraskeletal Myxoid Chondrosarcoma (EMC): For EMC sample size is obtained for the primary endpoint of 6-month progression-free survival rate, and estimated accrual 24 months. A 6-m PFSR of 50% will be considered not promising whereas of 80% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 22 patients were estimated in this cohort. With Simon's two-stage Minimax design, at least 13 cases over the 20 first patients (stage 1) should have a 6-m PFSR. Then additional 2 patients would be accrued up to 22 patients. If at least 15 patients had a 6-m PFSR, further investigation of the drug is warranted.
COHORT 3 - Vascular sarcomas (VS) (including angiosarcoma, hemangioendothelioma and intimal sarcomas): For VS sample size is obtained for the primary endpoint of 6-month progression-free survival rate, and estimated accrual 24 months. A 6-m PFSR of 30% will be considered not promising whereas of 60% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 23 patients were estimated in this cohort. With Simon's two-stage Minimax design, at least 8 cases over the 18 first patients (stage 1) should have a 6-m PFSR. Then additional 5 patients would be accrued up to 23 patients. If at least 11 patients had a 6-m PFSR, further investigation of the drug is warranted.
COHORT 4 - Solitary Fibrous Tumor (SFT): For SFT cohort sample size is obtained for the primary endpoint of 6-month progression-free survival rate by Choi criteria, and estimated accrual of 24 months. A 6-m PFSR of 35% will be considered not promising whereas of 65% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 24 patients were estimated in this cohort. With Simon's two-stage Minimax design, at least 6 cases over the 14 first patients (stage 1) should have a 6-m PFSR. Then additional 10 patients would be accrued up to 24 patients. If at least 13 patients had a 6-m PFSR, further investigation of the drug is warranted.
COHORT 5 - Alveolar Soft Part Sarcoma (ASPS): For ASPS cohort sample size is obtained for the primary endpoint of 12-month progression-free survival rate by RECIST criteria, and estimated accrual 24 months. A 12-m PFSR of 40% will be considered not promising whereas of 75% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 18 patients were estimated in this cohort. With Simon's two stage Minimax design, at least 7 cases over the 12 first patients (stage 1) should have a 12-m PFSR. Then additional 6 patients would be accrued up to 18 patients. If at least 11 patients had a 12-m PFSR, further investigation of the drug is warranted.
COHORT 6 - Clear Cell Sarcoma (CCS): For CCS cohort sample size is obtained for the primary endpoint of 6-month progression-free survival rate by RECIST criteria, and estimated accrual 24 months. A 6-m PFSR of 25% will be considered not promising whereas of 55% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.90, 23 patients were estimated in this cohort. With Simon's two-stage Minimax design, at least 4 cases over the 13 first patients (stage 1) should have a 6-m PFSR. Then additional 10 patients would be accrued up to 23 patients. If at least 10 patients had a 6-m PFSR, further investigation of the drug is warranted. An additional 5-7% of patients may be recruited to compensate for potential unevaluable participants.For the variables that follow binomial distributions, like the PFS rate and for the categorical variables, frequencies and percentages will be calculated as well as their confidence interval. If needed, to compare categorical variables both Chi-square test and Fisher's exact test will be performed. Besides, Kaplan-Meier estimations will be used for PFS. Where possible, exploratory analysis will include Cox models to estimate the impact of several factors on PFS.
Cohort 7: This cohort includes a phase 1b study (3+3 design plus expansion cohorts) and therefore no formal sample size has been calculated. Each subcohort (7a: UPS and 7b: LMS) will include between 10 and 20 patients respectively (including the expansions).
Cohort 8: A phase I/II is planned for this cohort. For the phase I part, the safety of the MAP + nivolumab combination will be assessed using a 3+3 design including 6 patients treated at the recommended phase II dose (RP2D). This phase I could include up to 12 patients approximately. Regarding the phase II part, for osteosarcoma with metastasis at presentation and resectable primary tumor, in patients with less than 40 years, sample size is obtained for the primary endpoint of histological response after 2 MAPs of induction. A proportion of 45% of good histological response (≥90% necrosis) will be considered not promising, whereas 68% will be considered promising in this population. With a type I error α of 0.05 and a power of 0.80, 31 patients were estimated in this cohort. With Simon's two-stage Minimax design, at least 7 cases over the 13 first patients (initial part) should have good histological response. Then, additional 18 eligible patients will be accrued up to 31 patients. If at least 19 patients had good histological response, further investigation of the drug is warranted.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 197
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Sunitinib 37.5 MG, Sunitinib 25 MG [Sutent] Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Nivolumab 100 MG/10 ML [Opdivo] Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Epirubicin Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Ifosfamide Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Dacarbazine Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Doxorubicin Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Cisplatin Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364. Sunitinib and/or nivolumab plus chemotherapy in advanced STS and BS Methotrexate Stage 1: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 37.5mg/d+nivolumab 3mg/kg ev 2w. Stage 2: C1-6: IP d1-14 sunitinib 37.5mg/d then MP sunitinib 25mg/d+nivolumab 240mg ev 2w. C7a level 0: Epirubicin 60mg/m2/d, d1,2, ifosfamide 3g/m2/d d1-3 and nivolumab 360mg. 3 or more DLTs level -1 same treatment than in level 0, but nivolumab 240mg. C7b level 0: Doxorubicin 75mg/m2/d, d1, dacarbazine 400mg/m2/d (also on d2) and nivolumab 360mg. 3 or more DLTs level -1 same tratment than in level 0, but nivolumab 240mg. GCSF support is mandatory. 1-year maintenance of nivolumab. C8 level 0: In the IP, CDDP 120mg/m2 (d1-2), doxorubicin 75mg/m2 in (d3-4 and d36-39), nivolumab 240mg (d5), and on d18,39,53 and methotrexate 12g/m2 on d22,29,57,64, surgery and MP with nivolumab on d210, every 2 weeks up to d364. 3 or more DLTs level -1, with nivolumab 360mg on d4,36, surgery and MP with nivolumab on d210, ev 3 weeks up to d364.
- Primary Outcome Measures
Name Time Method Stage 1 - PHASE 2 6 months Progression-free survival rate (PFSR): 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 enrollment until month 6 after enrollment.
Stage 1 - PHASE 1 6 months The recommended dose of the sunitinib and nivolumab combination for phase II part will be determined by assessing adverse events according to CTCAE 4.0 and they will be used as a rule for escalating or diminishing dose levels according to the dose-limiting toxicities detailed in the protocol
Stage 2 - Cohort 8: Maximum tolerated dose (MTD) 1 year The maximum tolerated dose (MTD) of the MAP + nivolumab combination will be determined by assessing adverse events according to CTCAE 5.0 and they will be used for adjusting dose levels according to the dose-limiting toxicities detailed in the protocol.
Stage 2 - Cohort 1-6: Progression-free survival rate (PFSR) 6 months for CS/DDCS, EMC, VS, SFT, and CCS and 12 months for ASPS CS/DDCS, EMC, VS, SFT, and CCS cohorts: 6-month progression-free survival rate (PFSR): 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 enrollmentuntil month 6 after enrollment.
ASPS cohort: 12-month progression-free survival rate (PFSR): Efficacy measured by the PFSR at 12 months according to RECIST 1.1. PFSR at 12 months is defined as the percentage of patients who did not experience progression or death due to any cause since the date of enrollment until month 12 after enrollment.Stage 2 - Cohort 7: Maximum tolerated dose (MTD) 1 year The maximum tolerated dose (MTD) of the epirubicin + ifosfamide + nivolumab combination will be determined by assessing adverse events according to CTCAE 5.0 and they will be used for adjusting dose levels according to the dose-limiting toxicities detailed in the protocol.
- Secondary Outcome Measures
Name Time Method Stage 1 and Stage 2 - Overall survival (OS) 2 years OS is defined as the time between the date of enrollment and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.
Stage 1 and Stage 2 - Objective response rate (ORR) 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).
Stage 2 - Cohort 1-6 Correlation between efficacy and potential predictive biomarkers 2 years Assessed by finding relationships between clinical efficacy results and translational data.
Stage 1 and Stage 2 - Safety profile: Adverse events 3 years 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 5.0.
Stage 1 (PHASE 2) and Stage 2 - Cohort 1-6 Clinical outcome At 36 months Clinical outcomes of post protocol treatments assessed by observation of such treatments in follow-up stage.
Stage 2 - Cohort 1-6 Prognostic and response correlation 1 month Prognostic and response correlation with neutrophils/platelets; lymphocytes/platelets; andred blood cell distribution width (RDW), by assessing hematology tests at baseline, after 2 weeks (before nivolumab), after 1 month, at progression, and at response.
Stage 1 (PHASE 1) and Stage 2 - Cohort 1-6 6-month progression-free survival rate (PFSR) 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 date of enrollment until month 6 after enrollment.
Stage 2 - Cohort 7 Median progression-free survival (mPFS) 6 months PFS is defined as the time between the date of enrollment and the date of progression or death due to any cause.
Stage 2 - Cohort 7 Median overall survival (mOS) 2 years OS is defined as the time between the date of enrollment and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.
Stage 2 - Cohort 8 Pathological response At month 3 Measured by percentage of necrosis in surgical specimen.
Stage 1 (PHASE 2) 3 years Efficacy measured through tumor response according to Choi criteria. The evaluation criteria will be based on the identification of target lesions in baseline and their follow up until tumor progression
Trial Locations
- Locations (13)
Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Hospital Universitario Virgen del Rocío
🇪🇸Sevilla, Spain
Hospital Universitari i Politècnic La Fe
🇪🇸Valencia, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Istituto Ortopedico Rizzoli
🇮🇹Bologna, Italy
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Candiolo Cancer Institute - FPO, IRCCS
🇮🇹Candiolo, Italy
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Complejo Hospitalario Universitario de Canarias
🇪🇸La Laguna, Santa Cruz De Tenerife, Spain
Hospital Universitario Fundación Jiménez Díaz
🇪🇸Madrid, Comunidad De Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom