Combination of pembrolizumab and cabozantinib in patients with advanced sarcomas
- Conditions
- Advanced /metastatic sarcomas: undifferentiated pleomorphic sarcoma, osteosarcoma and Ewing sarcomaMedDRA version: 20.0Level: LLTClassification code 10039494Term: Sarcoma NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-002366-13-FR
- Lead Sponsor
- Institut Bergonié
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 119
1. Histology: undifferentiated pleomorphic sarcoma (stratum 1), osteosarcoma (stratum 2) or Ewing sarcoma (stratum 3). Diagnosis must be reviewed or confirmed by the RRePS Network as recommended by the French NCI (Inca),
2. Advanced non resectable / metastatic disease,
3. Recurrent disease or progression after standard therapy,
4. Documented progression according to RECIST criteria. Progression on the last line of treatment should be confirmed by central review with two radiological assessments identical (CT scans or MRI) obtained at less than 6 months interval within the 12 months before inclusion, except if first line of recurrence,
5. Have provided tissue of a tumor lesion from < 3 months old archival tissue sample obtained on locally advanced disease, or metastatis with no subsequent treatment since or from a newly obtained core or excisional biopsy,
6. No more of three previous lines of systemic therapy for advanced disease,
7. Age = 18 years,
8. Eastern Cooperative Oncology Group (ECOG) performance status = 1,
9. Measurable disease according to RECIST v1.1 outside any previously irradiated field. At least one site of disease must be uni-dimensionally = 10 mm,
10. Life expectancy > 3 months,
11. Participant must have advanced disease and must not be a candidate for other approved therapeutic regimen known to provide significant clinical benefit based on investigator judgement,
12. No symptomatic central nervous system disease,
13. No chronic use of glucocorticoids.
14. Adequate hematological, renal, metabolic and hepatic function:
a. Hemoglobin = 9 g/dl (without erythropoietin dependency and without red blood cel transfusion within the last two weeks); absolute neutrophil count (ANC) = 1.5 G/l, lymphocytes count = 0.5 G/l and platelet count = 100 G/l,
b. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x upper limit of normality (ULN) (= 5 in case of liver metastasis).
c. Total bilirubin = 1.5 x ULN OR Direct bilirubin = ULN for subjects with total bilirubin levels = 1.5 x ULN.
d. Albumin = 25g/l.
e. Serum creatinine = 1.5 x ULN OR Calculated creatinine clearance (CrCl) = 60 ml/min (calculated per institutional standard) for subject with creatinine levels = 1.5 x ULN.
f. Creatine phosphokinase (CPK) = 2.5 x ULN
g. International normalized ratio (INR) OR prothrombin time (PT), activated partial thromboplastine time (aPTT) = 1.5 x ULN.,
h. Lipase = 2 x ULN and no radiological or clinical evidence of pancreatitis,
i. Urine protein/creatinine ratio (UPCR) = 1,
15. No prior or concurrent malignant disease diagnosed or treated in the last 2 years except for adequately treated in situ carcinoma of the cervix, basal or squamous skin cell carcinoma, or in situ transitional bladder cell carcinoma,
16. At least three weeks since last chemotherapy, immunotherapy and two weeks for any other pharmacological treatment and/or radiotherapy,
17. Recovery to grade = 1 from any adverse event (AE) derived from previous treatment (excluding alopecia of any grade, non-painful peripheral neuropathy grade = 2 and endocrine-related grade = 2 requiring treatment or hormone replacement) (according to the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE, version 5.0). For patients previously treated by radiotherapy, they must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis,
18. Women of childbearing
1. Previous treatment with Pembrolizumab or Cabozantinib,
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumabor any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways),
3. Evidence of progressive or symptomatic central nervous system (CNS) or leptomeningeal metastases,
4. Men or women of childbearing potential who are not using an effective method of contraception; women who are pregnant or breast feeding, men or women who are planning to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment,
5. Participation to a study involving a medical or therapeutic intervention in the last 21 days,
6. Previous enrolment in the present study,
7. Patient unable to follow and comply with the study procedures because of any geographical, familial, social or psychological reasons,
8. Patient unable to swallow,
9. Known hypersensitivity to any involved study drug or of its formulation components,
10. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg. Thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc…) is not considered a form of systemic treatment and is allowed.
11. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment,
12. History of idiopathic pulmonary fibrosis, history of non-infectious pneumonitis that required steroids, current pneumonitis/interstitial lung disease, drug-induced pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted,
13. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection (HIV1/2 antibodies) and/or of active TB (Bacillus Tuberculosis),
15. Treatment with anticoagulants such as anti-Vitamin K, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel),
16. Previous allogenic bone marrow transplant or solid organ transplantation,
17. Has an active infection requiring systemic treatment at study entry,
18. The subject has a corrected QT interval calculated by the Fridericia formula (QTcF) > 500 ms within 28 days before treatment. Note: if initial QTcF is found to be > 500 ms, two additional ECGs separated by at least 3 minutes should be performed. If the average of these three consecutive results for QTcF is = 500 ms, the subject meets eligibility in this regard,
19. The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John’s Wort). Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians’ De
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method