Informations générales (source: ClinicalTrials.gov)
Combination of Pembrolizumab and Cabozantinib in Patients With Advanced Sarcomas
Interventional
Phase 2
Institut Bergonié (Voir sur ClinicalTrials)
avril 2022
octobre 2025
29 août 2025
Phase II trial with three independent strata to independently assess the effects of the
association of pembrolizumab and cabozantinib in advanced sarcomas.
Etablissements
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | Sarah WATSON, MD | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Benjamin VERRET, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Georges François Leclerc - 21079 - Dijon - France | Isabelle DESMOULINS, MD | Contact (sur clinicalTrials) | |||
| Centre Leon Berard - 69008 - Lyon - France | Armelle DUFRESNE, MD | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - 59020 - Lille - France | Loic LEBELLEC, MD | Contact (sur clinicalTrials) | |||
| Hôpital La Timone - 13385 - Marseille - France | Florence DUFFAUD, MD, PhD | Contact (sur clinicalTrials) | |||
| Institut Bergonie - 33076 - Bordeaux - France | Maud TOULMONDE, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancérologie de l'Ouest - Site René Gauducheau - 44805 - Saint-Herblain - France | Emmanuelle BOMPAS, MD | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - 13009 - Marseille - France | Francois BERTUCCI, MD, PhD | Contact (sur clinicalTrials) | |||
| IUCT Oncopole - 31059 - Toulouse - France | Thibaud VALENTIN, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Histology: undifferentiated pleomorphic sarcoma (stratum 1), bone osteosarcoma
(stratum 2), bone or extraskeletal or Ewing sarcoma (stratum 3),
2. Advanced non resectable / metastatic disease,
3. Recurrent disease or progression after standard therapy,
4. Documented progression according to RECIST criteria.
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 ≤ 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,
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 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 potential must have a negative serum pregnancy test within 72
hours prior to receiving the first dose of study medication. Both women and men must
agree to use 2 medically acceptable methods of contraception throughout the
treatment period and for 6 months after discontinuation of treatment. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for ≥ 1 year,
19. Voluntary signed and dated written informed consents prior to any specific study
procedure,
20. Patients with a social security in compliance with the French Law.
1. Histology: undifferentiated pleomorphic sarcoma (stratum 1), bone osteosarcoma
(stratum 2), bone or extraskeletal or Ewing sarcoma (stratum 3),
2. Advanced non resectable / metastatic disease,
3. Recurrent disease or progression after standard therapy,
4. Documented progression according to RECIST criteria.
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 ≤ 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,
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 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 potential must have a negative serum pregnancy test within 72
hours prior to receiving the first dose of study medication. Both women and men must
agree to use 2 medically acceptable methods of contraception throughout the
treatment period and for 6 months after discontinuation of treatment. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for ≥ 1 year,
19. Voluntary signed and dated written informed consents prior to any specific study
procedure,
20. Patients with a social security in compliance with the French Law.
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 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 an 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 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 HIV infection 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
20. The subject has experienced any of the following: Clinically-significant
gastrointestinal bleeding within 6 months before the first dose of study treatment,
Hemoptysis of ≥ 2.5 mL of red blood within 3 months before the first dose of study
treatment, Any other signs indicative of pulmonary hemorrhage within 3 months before
the first dose of study treatment, The subject has radiographic evidence of
cavitating pulmonary lesion(s), The subject has tumor in contact with, invading or
encasing any major blood vessels, or The subject has evidence of tumor invading the
GI tract, or any evidence of endotracheal or endobronchial tumor within 28 days
before the first dose of cabozantinib.
21. The subject has uncontrolled, significant intercurrent or recent illness including,
but not limited to, the following conditions which are fully described in the study
protocol: Cardiovascular disorders, Gastrointestinal disorders particularly those
associated with a high risk of perforation or fistula formation, Other disorders
associated with a high risk of fistula formation including PEG tube placement within
3 months before the first dose of study therapy,
22. Has received a live vaccine within 30 days prior to the first dose of study drug.
Examples of live vaccines include, but are not limited to, the following: measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
Calmette-Guérin (BCG), and typhoid vaccine. Note: Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
23. Has an history or current evidence of any condition, therapy, or laboratory
abnormality that might counfound the results of the study, interfere with the
subject's participation for the full duration of the study, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
24. The subject is planning to have oral surgery/invasive dental procedure within the
projected duration of the study, starting with the screening visit through 3 months
after the last dose of study treatment or had such a procedure within 3 months of
first dose of study treatment.