Informations générales (source: ClinicalTrials.gov)
Phase Ib Trial Of Pembrolizumab And Nintedanib
Interventional
Phase 1
Gustave Roussy, Cancer Campus, Grand Paris (Voir sur ClinicalTrials)
novembre 2016
novembre 2028
04 septembre 2025
Both anti-angiogenesis and anti PD1 immunotherapy have shown beneficial efficacy in solid
tumors and in particular in NSCLC. Therefore it is of interest to investigate whether the
combination of these two approaches is tolerable. Moreover, comprehensive pre-clinical
and clinical rationale sustain the hypothesis that anti-VEGF could synergize with
immunotherapy for the benefit of the patients.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Capucine BALDINI | 20/06/2024 12:46:17 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Bichat | 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 Léon Bérard - 69008 - Lyon - France | Philippe Cassier | Contact (sur clinicalTrials) | |||
| Institut Bergonié - 33000 - Bordeaux - France | Antoine ITALIANO | Contact (sur clinicalTrials) | |||
| IUCT--O - 31059 - Toulouse - France | Carlos Gomez-Roca | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Age ≥ 18
2. Patients with advanced/metastatic cancer who have progressed after at least one line
of standard therapy or are intolerant to standard therapy. Patients must fit into
one of the following groups:
Colorectal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC)
Gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either
PCR and/or IHC Patients with advanced or metastatic Urothelial cancer (UC) Patients
with advanced Renal Cell cancer (RCC) Patients with advanced Mesothelioma (MPM)
Patients with advanced squamous cell carcinoma in Cervical Cancer (CC) Patients with
advanced Hepatocellular (HCC) Patients with advanced Thymic Carcinoma (TC) Patients
with advanced cancers and high tumor mutational burden (TMB-High) on their
circulating tumor DNA (ctDNA) as defined by more than twenty mutations per megabase
(≥20Mut/Mb) on FoundationOne Liquid CDx assay. Patients should be without known
therapeutic options to provide clinical benefit.
3. ECOG performance status of score 0 or 1
4. Adequate organ function as defined by the following criteria :
- Proteinuria ≤ Grade 2 NCI CTCAE v4.03
- Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min
- Total bilirubin within normal range (≤ 1.5 x ULN if HCC)
- AST and ALT ≤ 1.5 x upper limit of normal (ULN); if liver metastases AST and
ALT ≤ 2.5 x ULN (≤ 5 x ULN if HCC)
- Coagulation parameter : International normalized ratio (INR) < 2, prothrombin
time (PT) and partial thromboplastin time (PTT) < 50% of deviation of ULN
- Absolute Neutrophils count (ANC) ≥ 1000 cells/mm^3
- Platelets ≥100 000 cells/mm^3
- Hemoglobin ≥ 9.0 g/dL
5. At least one measurable lesion according to RECIST v1.1 (Appendix 4) criteria and
modified RECIST for mesothelioma only (Appendix 6) or any other baseline
prerequisite for the assessment of the principal judgment criteria.
6. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test within 7 days prior to initiation of treatment. Both sexually active
females and males (and their female partners) patients must agree to use two methods
of effective contraception, one of them being a barrier method, or to abstain from
sexual activity during the study and for at least 4 months after last study drug
administration.
7. Signed and dated written informed consent prior to admission to the study
8. Patient affiliated to a social security regimen or beneficiary of the same
1. Age ≥ 18
2. Patients with advanced/metastatic cancer who have progressed after at least one line
of standard therapy or are intolerant to standard therapy. Patients must fit into
one of the following groups:
Colorectal adenocarcinoma (not mismatch repair deficient by either PCR and/or IHC)
Gastric or gastroesophageal adenocarcinoma (not mismatch repair deficient by either
PCR and/or IHC Patients with advanced or metastatic Urothelial cancer (UC) Patients
with advanced Renal Cell cancer (RCC) Patients with advanced Mesothelioma (MPM)
Patients with advanced squamous cell carcinoma in Cervical Cancer (CC) Patients with
advanced Hepatocellular (HCC) Patients with advanced Thymic Carcinoma (TC) Patients
with advanced cancers and high tumor mutational burden (TMB-High) on their
circulating tumor DNA (ctDNA) as defined by more than twenty mutations per megabase
(≥20Mut/Mb) on FoundationOne Liquid CDx assay. Patients should be without known
therapeutic options to provide clinical benefit.
3. ECOG performance status of score 0 or 1
4. Adequate organ function as defined by the following criteria :
- Proteinuria ≤ Grade 2 NCI CTCAE v4.03
- Serum creatinine ≤1.5 x ULN or calculated creatinine clearance ≥ 40 mL/min
- Total bilirubin within normal range (≤ 1.5 x ULN if HCC)
- AST and ALT ≤ 1.5 x upper limit of normal (ULN); if liver metastases AST and
ALT ≤ 2.5 x ULN (≤ 5 x ULN if HCC)
- Coagulation parameter : International normalized ratio (INR) < 2, prothrombin
time (PT) and partial thromboplastin time (PTT) < 50% of deviation of ULN
- Absolute Neutrophils count (ANC) ≥ 1000 cells/mm^3
- Platelets ≥100 000 cells/mm^3
- Hemoglobin ≥ 9.0 g/dL
5. At least one measurable lesion according to RECIST v1.1 (Appendix 4) criteria and
modified RECIST for mesothelioma only (Appendix 6) or any other baseline
prerequisite for the assessment of the principal judgment criteria.
6. Women of childbearing potential (WOCBP) must have a negative serum or urine
pregnancy test within 7 days prior to initiation of treatment. Both sexually active
females and males (and their female partners) patients must agree to use two methods
of effective contraception, one of them being a barrier method, or to abstain from
sexual activity during the study and for at least 4 months after last study drug
administration.
7. Signed and dated written informed consent prior to admission to the study
8. Patient affiliated to a social security regimen or beneficiary of the same
1. Prior treatment with nintedanib
2. Known hypersensitivity to trial drugs or their excipients, peanut or soya or to
contrast media
3. Prior treatment with pembrolizumab or any other anti PD1 or anti-PDL1 agents
4. Concurrent steroid medication (except topical or aerosol steroids). Any steroid
medication should have been stopped for more than 7 days prior beginning of therapy.
5. History of autoimmune/immune mediated inflammatory disease, including but not
limited to colitis, pneumonitis, hepatitis, hypophysitis, nephritis,
hyperthyroidism, systemic lupus erythematous, rheumatoid arthritis, inflammatory
bowel disease, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré
syndrome, vasculitis, or glomerulonephritis (see Appendix 3). Patients with a
history of auto-immune endocrinopathy (hypo/hyper thyroiditis, type 1 diabetes
mellitus, ...) and who are stable on hormone replacement therapy are eligible for
the study. Patients with a history of vitiligo, pelade, cutaneous psoriasis and
grade 1-2 Sjogren syndrome are eligible.
6. Chemo-, hormono-, radio- (except for brain and extremities) or immunotherapy or
therapy with monoclonal antibodies or small tyrosine kinase inhibitors within the
past 4 weeks or 5 half-life times (whatever the shortest) prior to treatment with
the trial drugs.
7. Administration of a live, attenuated vaccine within 4 weeks before registration
8. Treatment with systemic immunosuppressive medications (including but not limited to
steroids azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor
[anti-TNF] agents) within 2 weeks prior to registration
9. Radiotherapy to the target lesion (unless a progression after radiotherapy has been
documented)
10. Persistence of clinically relevant treatment-related toxicity from previous
chemotherapy, targeted therapy and/or radiotherapy
11. Active brain metastases or leptomeningeal disease. Clinically asymptomatic brain
metastases and clinically asymptomatic leptomeningeal disease are allowed (treatment
with steroids prior initiation of the trial is not allowed). Patients with Diffuse
Intrinsic Pontine Gliomas, even asymptomatic, are not allowed.
12. Radiographic evidence of cavitary tumors with local invasion of major blood vessels
and/or at risk for perforation
13. History of clinically significant hemoptysis within the past 3 months (more than one
teaspoon of fresh blood per day)
14. Treatment with other investigational drugs or treatment in another clinical trial
within the past 4 weeks before start of therapy or concomitantly with the trial
15. Therapeutic anticoagulation with drugs requiring INR monitoring (except low-dose
heparin and/or heparin flush as needed for maintenance of an in-dwelling intravenous
devise) or anti-platelet therapy (except for low-dose therapy with acetylsalicylic
acid < 325mg per day)
16. Major injuries and/or surgery within the past 4 weeks prior to start of study
treatment with incomplete wound healing and/or planned surgery during the
on-treatment study period
17. History of clinically significant hemorrhagic or thromboembolic event in the past 6
months
18. Known inherited (genetic) predisposition to bleeding or thrombosis (such deficit in
protein C/S) or acquired predisposition to thrombosis (such as anti-phospholipid
syndromes)
19. History of significant cardiovascular diseases ( i.e. supraventricular tachycardia,
uncontrolled hypertension, unstable angina, history of infarction within the past 12
months prior to start of study treatment, congestive heart failure > NYHA II,
serious cardiac arrhythmia, pericardial effusion)
20. Ongoing uncontrolled auto-immune thyroiditis. Ancient thyroiditis currently stable
with substitutive therapy should not be excluded from the trial.
21. Other malignancies within the past 5 years other than basal cell skin cancer or
carcinoma in situ of the cervix. A history of more than 3 years of local prostate
cancer treated by surgery and without PSA elevation since surgery, or local breast
carcinoma treated by surgery without relapse are eligible.
22. Active serious infections in particular if requiring systemic antibiotic or
antimicrobial therapy
23. Known to be human immunodeficiency virus (HIV) positive;
24. Gastrointestinal disorders or abnormalities that would interfere with absorption of
the study drug
25. Serious illness or concomitant non-oncological disease such as neurologic,
psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or
laboratory abnormality that may increase the risk associated with study
participation or study drug administration and in the judgment of the investigator
would make the patient inappropriate for entry into the study.
26. Pregnancy or breast feeding,
27. Psychological, familial, sociological or geographical factors potentially hampering
compliance with the study protocol and follow-up schedule
28. Active alcohol or drug abuse
29. Intake of Ganoderma Lucidum mushroom and/or herbal remedies and/or traditional
medicines within the past 4 weeks prior to start of study treatment or concomitantly
with the trial