Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02517918
Other study ID # IB 2014-01
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date February 2015
Est. completion date November 16, 2021

Study information

Verified date November 2022
Source Institut Bergonié
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a prospective open-labeled phase I trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the Maximum Tolerated Dose (MTD) is established.


Description:

The dose escalation part of the trial will be concerned on adults with advanced solid tumor with bone metastasis and young and adult patients with unresectable locally advanced or metastatic osteosarcoma. The Expansion cohort will be conducted on young and adult patients with unresectable locally advanced or metastatic osteosarcoma.


Recruitment information / eligibility

Status Completed
Enrollment 23
Est. completion date November 16, 2021
Est. primary completion date September 5, 2016
Accepts healthy volunteers No
Gender All
Age group 13 Years and older
Eligibility Inclusion Criteria: 1. Histology: - Advanced solid tumor with radiologically proven bone metastasis, (dose escalation part) - Patients with osteogenic osteosarcoma (dose escalation part and expansion cohort) histologically confirmed by central review 2. Metastatic or unresectable locally advanced disease, not eligible for alternative local treatment (radiotherapy for instance) 3. Age > 18 years for patients with solid tumor and = 13 years for patients with osteosarcoma 4. ECOG, performance status = 1 5. Life expectancy > 3 months 6. Measurable disease according to RECIST v1.1. At least one site of disease must be uni-dimensionally = 10 mm 7. Patients must have histologically confirmed diagnosis of locally advanced and/or metastatic solid tumors, which are not amenable to standard treatment, including for patients with osteosarcoma conventional agents such as anthracyclines, platinum salts, ifosfamide and/or methotrexate 8. At least three weeks since last chemotherapy, immunotherapy or any other pharmacological treatment and/or radiotherapy 9. Adequate haematological, renal, metabolic and hepatic function: - Haemoglobin = 10 g/dl (patients may have received prior red blood cell transfusion, if clinically indicated); leucocytes = 3 x 10^9/l, absolute neutrophil count = 1.5 x 10^9/l, and platelet count = 120 x 10^9/l. - Alanine aminotransferase and aspartate aminotransferase = 2.5 x upper limit of normality (ULN) - Total bilirubin = 1.5 x ULN - Calculated creatinine clearance > 40 ml/min/1.73 m² (according to MDRD formula) - Creatine phosphokinase = 2.5 x ULN - Albumin > 25 g/l 10. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma, 11. Recovery to grade = 1 from any adverse event derived from previous treatment (excluding alopecia of any grade and non-painful peripheral neuropathy grade = 2) according to the NCI-CTCAE, version 4 12. Patients with a French social security in compliance with the French law relating to biomedical research 13. Voluntarily signed and dated written informed consent prior to any study specific procedure 14. Women of childbearing potential must have a negative serum pregnancy test before study entry. Both women and men must agree to use a medically acceptable method of contraception throughout the treatment period and for six months after discontinuation of treatment Exclusion Criteria: 1. Previous treatment with sirolimus 2. Concomitant diseases/conditions: - Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions - Unstable cardiac disease, pulse oximetry saturation < 90% at rest - Clinically significant immunodeficiency, such as HIV or active Hepatitis B or C - History of auto-immune disease, transplantation 3. Central nervous system malignancy 4. Men or women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding 5. Patients receiving any substances that are inhibitors or inducers of CYP450 3A4 6. Ongoing or recent (<6 weeks) dental problem, including any severe tooth or jaw infection (mandible and maxilla), dental trauma, dental or stomatological surgery (implants). Current dental cares are allowed 7. History of maxillary osteonecrosis or delayed healing after dental surgery 8. Participation to a study involving a medical or therapeutic intervention in the last 30 days 9. Previous enrolment in the present study 10. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons 11. Known hypersensitivity to any involved study drug or any of its formulation components 12. Patients receiving live vaccines within 30 days prior to the first dose of study therapy and while participating in study

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Sirolimus combined with CP, MT and ZA
Cyclophosphamide, Methotrexate and Sirolimus will be administrated orally. Zoledronic Acid will be administrated by infusion (IV). Trial based on a dose escalating study design assessing two dose levels of sirolimus when prescribed in combination with metronomic cyclophosphamide (CP), methotrexate (MT) and zoledronic acid (ZA) followed by an expansion cohort once the MTD is established.

Locations

Country Name City State
France Institut Bergonié Bordeaux
France Centre Oscar Lambret Lille
France Centre Léon Bérard Lyon

Sponsors (3)

Lead Sponsor Collaborator
Institut Bergonié Pfizer, Reliable Cancer Therapies

Country where clinical trial is conducted

France, 

Outcome

Type Measure Description Time frame Safety issue
Primary Maximum tolerated dose (MTD) evaluated on the first cycle (D1 to D28) of sirolimus when administered in association with CP, MT and ZA During the first cycle (28 days
Secondary Recommended phase II dose (RP2D) of sirolimus when administered in association with CP, MT and ZA Throughout 6 month the treatment period
Secondary Documentation of any observed antitumor activity 6-month objective response rate (ORR) as per RECIST v1.1,best objective response rate (ORR) as per RECIST v1.1,6-month Non-progression rate (NPR) as per RECIST v1.1,1-year Progression-free survival (PFS) as per RECIST v1.1,1-year Overall Survival (OS)
Secondary PK measurements expressed as Area Under Curve for CP Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as Area Under Curve for MT Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as Area Under Curve for Sirolimus Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as half-life for CP Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as half-life for MT Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as half-life for Sirolimus Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as concentration peak for CP Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as concentration peak for MT Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary PK measurements expressed as concentration peak for Sirolimus Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary Dose Limiting Toxicities (DLT) of sirolimus when administered in association with CP, MT and ZA During the first cycle (28 days)
Secondary Safety profile of sirolimus when administered in association with CP, MT and ZA evaluated by monitoring the AEs through the NCI-CTC v4 Throughout the treatment period
Secondary Pharmacokinetics (PK) of sirolimus when administered in association with CP, MT and ZA Day 1 of cycle1, Day 18 of cycle1, Day 2 of cycle 2, Day 1 of cycle3, Day 1 of cycle 6, At progression
Secondary Predictive biomarkers (PD) of sirolimus when administered in association with CP, MT and ZA Day 1 of cycle 1, Day 18 of cycle 1, Day 1 of cycle 2, Day 1 of cycle 3, Day 1 cycle 4, Day 1 cycle 6, At progression which can occur at any time during the 6-month period.]
Secondary Antitumor activity of sirolimus when administered in association with CP, MT and ZA in terms of 6-month objective response rate (ORR) as per RECIST 1.1 6-month objective response rate
Secondary Antitumor activity of sirolimus when administered in association with CP, MT and ZA in terms of 6 month best objective response rate (ORR) as per RECIST v1.1 best objective response rate (ORR) as per RECIST
Secondary Antitumor activity of sirolimus when administered in association with CP, MT and ZA in terms of 6-month Non-progression rate (NPR) as per RECIST 1.1 6-month Non-progression rate (NPR) as per RECIST
Secondary Antitumor activity of sirolimus when administered in association with CP, MT and ZA in terms of 1-year Progression-free survival (PFS) as per RECIST 1.1 1-year Progression-free survival (PFS) as per RECIST
Secondary Antitumor activity of sirolimus when administered in association with CP, MT and ZA in terms of Growth modulation index (GMI) participants will be followed until progression, unexpected average of 4 month
Secondary Antitumor activity of sirolimus when administered in association with CP, MT and ZA in terms of 1-year Overall Survival (OS) 1-year Overall Survival (OS) as per RECIST
Secondary Exploration of blood cytokines levels (INF?, TNFa, TGFß, IL2, 4, 6, 10) (ELISA) Blood samples collected at different time points : Baseline, Day 1 cycle 1, Day 18 cycle 1, Day 1 cycle 2, Day 1 cycle 3, Day 1 Cycle 4, Day 1 Cycle 6 and at progression which can occur at any time during the 6-month period
Secondary Exploration of blood VEGF, PIGF and TPS-1 levels (ELISA) Blood samples collected at different time points : Baseline, Day 1 cycle 1, Day 18 cycle 1, Day 1 cycle 2, Day 1 cycle 3, Day 1 Cycle 4, Day 1 Cycle 6 and at progression which can occur at any time during the 6-month period
Secondary Exploration of lymphocytes subpopulations monitoring, CD8+, CD4+,Treg ratio (flow cytometry) Blood samples collected at different time points : Baseline, Day 1 cycle 1, Day 18 cycle 1, Day 1 cycle 2, Day 1 cycle 3, Day 1 Cycle 4, Day 1 Cycle 6 and at progression
Secondary Exploration of bone biomarkers such as PTH, vitamin D3, osteoclast activator and cytokine mediating Th1 immunity levels) Blood samples collected at different time points : Baseline, Day 1 cycle 1, Day 18 cycle 1, Day 1 cycle 2, Day 1 cycle 3, Day 1 Cycle 4, Day 1 Cycle 6 and at progression
See also
  Status Clinical Trial Phase
Recruiting NCT05580991 - Intratumoral CAN1012(Selective TLR7 Agonist) in Subjects With Solid Tumors Phase 1
Recruiting NCT05691608 - MoleculAr Profiling for Pediatric and Young Adult Cancer Treatment Stratification 2 N/A
Active, not recruiting NCT02846038 - Understanding Communication in Healthcare to Achieve Trust (U-CHAT)
Recruiting NCT05159388 - A Study of PRS-344/S095012 (PD-L1x4-1BB Bispecific Antibody-Anticalin Fusion) in Patients With Solid Tumors Phase 1/Phase 2
Completed NCT03181854 - Randomized Controlled Trial of Integrated Early Palliative Care N/A
Recruiting NCT06014502 - Study to Evaluate IMGS-001 Treatment in Patients With Relapsed or Refractory Advanced Solid Tumors Phase 1
Recruiting NCT05981703 - A Study Investigating BGB-26808 Alone or in Combination With Tislelizumab in Participants With Advanced Solid Tumors Phase 1
Recruiting NCT04107311 - Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients
Active, not recruiting NCT04078152 - Durvalumab Long-Term Safety and Efficacy Study Phase 4
Completed NCT02250157 - A Dose-regimen Finding Study to Evaluate Safety, Tolerability, Pharmacokinetics and Activity of Oratecan in Subjects With Advanced Malignancies Phase 1
Recruiting NCT05566574 - A Study of RP-3500 in Combination With Standard Radiation Therapy in People With Solid Tumor Cancer Phase 1/Phase 2
Recruiting NCT03943004 - Trial of DFP-14927 in Advanced Solid Tumors Phase 1
Recruiting NCT06036836 - Study of Favezelimab Coformulated With Pembrolizumab (MK-4280A) in Participants With Selected Solid Tumors (MK-4280A-010) Phase 2
Recruiting NCT05798546 - Treatment of Advanced Solid Tumors With Neo-T(GI-NeoT-02) Phase 1
Recruiting NCT05525858 - KPMNG Study of MOlecular Profiling Guided Therapy Based on Genomic Alterations in Advanced Solid Tumors II
Terminated NCT04586335 - Study of CYH33 in Combination With Olaparib an Oral PARP Inhibitor in Patients With Advanced Solid Tumors. Phase 1
Active, not recruiting NCT00479128 - Bortezomib With Gemcitabine/Doxorubicin in Patients With Urothelial Cancer and Other Solid Tumors Phase 1
Recruiting NCT04143789 - Evaluation of AP-002 in Patients With Solid Tumors Phase 1/Phase 2
Not yet recruiting NCT04550663 - NKG2D CAR-T(KD-025) in the Treatment of Relapsed or Refractory NKG2DL+ Tumors Phase 1
Completed NCT03980041 - Study to Evaluate the Efficacy/Safety of IPI-549 in Combination With Nivolumab in Patients With Advanced Urothelial Carcinoma (MARIO-275) Phase 2