Informations générales (source: ClinicalTrials.gov)
An Open-label Study of E7386 in Combination With Other Anticancer Drug(s) in Subjects With Solid Tumors
Interventional
Phase 1/Phase 2
Eisai Inc. (Voir sur ClinicalTrials)
juillet 2019
août 2027
03 juin 2025
The primary objective of this study is to assess the safety and tolerability and to
determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other
anticancer drug(s), and to determine the optimal dose of E7386 in combination with
lenvatinib in endometrial carcinoma (EC) (for EC Dose Optimization Part only).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Val�rie BOIGE | 05/06/2024 08:40:19 | 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 Beaujon | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Europeen Georges Pompidou | Contact (sur clinicalTrials) | ||||
| AP-HP - Hôpital Saint Antoine | Contact (sur clinicalTrials) | ||||
| CLCC INSTITUT CURIE | 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 | |||||
| AP-HP Université de Paris, Port Royal - 75014 Paris - Paris - France | Contact (sur clinicalTrials) | ||||
| Centre Antoine Lacassagne - 06100 Nice - Nice - France | Contact (sur clinicalTrials) | ||||
| Centre François Baclesse - 14000 Caen - Caen - France | Contact (sur clinicalTrials) | ||||
| Centre Georges-François Leclerc - 21000 - Dijon - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire (CHU) de Poitiers - 86000 Poitiers - Poitiers - France | Contact (sur clinicalTrials) | ||||
| Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)(Hopitaux de Bordeaux) - Groupe hospitalier Sud - Hopital Haut-Levequ - 33604 - Pessac - France | Contact (sur clinicalTrials) | ||||
| Centre Jean Perrin - 63000 Clermont-Ferrand - Clermont-Ferrand - France | Contact (sur clinicalTrials) | ||||
| Centre Léon Bérard - 69008 Lyon - Lyon - France | Contact (sur clinicalTrials) | ||||
| CHU Amiens-Picardie (Hopital Sud) - 80000 - Amiens - France | Contact (sur clinicalTrials) | ||||
| CHU Bordeaux - 33075 - Bordeaux - France | Contact (sur clinicalTrials) | ||||
| CHU Cavale Blanche - 29200 - Brest - France | Contact (sur clinicalTrials) | ||||
| CHU de LILLE - Hôpital HURIEZ - 59037 - Lille - France | Contact (sur clinicalTrials) | ||||
| Grenoble University Hospital (Centre Hospitalier Universitaire Grenoble Alpes) - 38700 - La Tronche - France | Contact (sur clinicalTrials) | ||||
| Hepatology, Hopital de la Croix-Rousse - 103 grande rue de la Croix-Rousse - 69004 - Lyon - France | Contact (sur clinicalTrials) | ||||
| Hopital de la Croix Saint-Simon - 75020 - Paris - France | Contact (sur clinicalTrials) | ||||
| ICANs - 67200 Strasbourg - Strasbourg - France | Contact (sur clinicalTrials) | ||||
| Insitute de Cancérologie de l'Ouest - Centre René Gauducheau - Saint-Herblain 44800 - Saint-Herblain - France | Contact (sur clinicalTrials) | ||||
| Institut Paoli-Calmettes - 3009 Marseille - Marseille - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
1. HCC part only:
Participants with confirmed diagnosis of unresectable HCC with any of the following
criteria:
1. Histologically or cytologically confirmed diagnosis of HCC, excluding
fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
2. Clinically confirmed diagnosis of HCC according to American Association for the
Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology
and/or chronic hepatitis B or C infection
ST part only (except for HCC):
Participants with histologically or cytologically confirmed diagnosis of solid tumor
for which no alternative standard therapy or no effective therapy exists
2. Life expectancy of >=12 weeks
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
4. All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1
except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver
function should meet the inclusion criteria)
5. Adequate washout period before study drug administration:
1. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is
shorter
2. Any antitumor therapy with antibody: 4 weeks or more
3. Any investigational drug or device: 4 weeks or more
4. Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2
weeks or more Note: Participants must have recovered from all radiation-related
toxicities, not require corticosteroids, and not had radiation pneumonitis
6. Adequate controlled blood pressure (BP), renal function, bone marrow function, liver
function, and serum mineral level
7. At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation
Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all
subparts in Expansion and Dose Optimization Parts) meeting following criteria
- At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a
non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is
serially measurable according to RECIST 1.1 using computerized tomography
(CT)/magnetic resonance imaging (MRI)
- Lesions that have had external beam radiotherapy or loco-regional therapies
such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/
transarterial embolization (TAE) must show evidence of progressive disease
based on RECIST 1.1 to be deemed a target lesion
8. For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more
was observed during Screening or Baseline, the participant is ineligible and
re-assessment of the Child-Pugh score is not permitted
9. For HCC participants only: Participants categorized to stage B (not amenable to
locoregional therapy or refractory to locoregional therapy, and not amenable to a
curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC)
staging system
10. For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced
or metastatic disease is as defined below
a. Participants who have received only one prior line of immuno oncology (IO) based
regimen and have progressed on or after prior treatment with IO based regimen, or IO
ineligible participants who have received no prior systemic therapy. Participants
who previously received lenvatinib treatment are ineligible
11. For CRC Subpart in Expansion Part only: participants must have received at least 2
prior regimens (not exceeding 4 prior regimens) or could not tolerate standard
treatment and must have received the following prior therapies in the metastatic
setting if approved and locally available (progressed on at least 1 prior regimen in
the metastatic setting or could not tolerate standard treatment):
Note: Adjuvant chemotherapy counts as prior systemic treatment if there is
documented disease progression within 6 months of treatment completion Note: If a
participant is determined to be intolerant to prior standard treatment, the
participant must have received at least of 2 cycles of that therapy Note:
Participants who have received oral tyrosine kinase inhibitor (example, regorafenib)
are ineligible
1. Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular
endothelial growth factor (VEGF) monoclonal antibody (mAb) (example,
bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidine
in prior treatment Note: Participants who have previously received
fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only
chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after
discussion with the Sponsor
2. Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab
or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat
sarcoma viral oncogene homolog [KRAS)/ NRAS]) wild type (WT) CRC Note: RAS
(KRAS/NRAS) WT participants with right or left CRC lesions who may have not
been treated with anti-EGFR mAb based on local guidelines are eligible
3. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E
mutated tumors
4. Immune checkpoint inhibitor for participants with microsatellite
instability-high (MSI-H) CRC
12. For EC Subpart in Expansion Part only: Participants must have EC that has progressed
after prior platinum-based chemotherapy and an anti-programmed cell death (ligand) 1
(PD-[L])1)-directed therapy for EC (participants ineligible for IO therapy who have
progressed after prior platinum-based chemotherapy are eligible). Up to 3 prior
systemic therapies, of which up to 2 for metastatic or locally advanced disease, are
permitted Note: There is no restriction regarding prior hormonal therapies For Dose
Optimization Part only: Participants must have EC that has progressed after prior
platinum-based chemotherapy and an anti-PD-(L)1-directed therapy for EC. Up to 3
lines of prior therapy, regardless of setting, are allowed. Note: Prior hormonal
therapy and radiation are allowed and do not count as prior lines of therapy.
1. HCC part only:
Participants with confirmed diagnosis of unresectable HCC with any of the following
criteria:
1. Histologically or cytologically confirmed diagnosis of HCC, excluding
fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
2. Clinically confirmed diagnosis of HCC according to American Association for the
Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology
and/or chronic hepatitis B or C infection
ST part only (except for HCC):
Participants with histologically or cytologically confirmed diagnosis of solid tumor
for which no alternative standard therapy or no effective therapy exists
2. Life expectancy of >=12 weeks
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
4. All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1
except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver
function should meet the inclusion criteria)
5. Adequate washout period before study drug administration:
1. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is
shorter
2. Any antitumor therapy with antibody: 4 weeks or more
3. Any investigational drug or device: 4 weeks or more
4. Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2
weeks or more Note: Participants must have recovered from all radiation-related
toxicities, not require corticosteroids, and not had radiation pneumonitis
6. Adequate controlled blood pressure (BP), renal function, bone marrow function, liver
function, and serum mineral level
7. At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation
Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all
subparts in Expansion and Dose Optimization Parts) meeting following criteria
- At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a
non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is
serially measurable according to RECIST 1.1 using computerized tomography
(CT)/magnetic resonance imaging (MRI)
- Lesions that have had external beam radiotherapy or loco-regional therapies
such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/
transarterial embolization (TAE) must show evidence of progressive disease
based on RECIST 1.1 to be deemed a target lesion
8. For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more
was observed during Screening or Baseline, the participant is ineligible and
re-assessment of the Child-Pugh score is not permitted
9. For HCC participants only: Participants categorized to stage B (not amenable to
locoregional therapy or refractory to locoregional therapy, and not amenable to a
curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC)
staging system
10. For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced
or metastatic disease is as defined below
a. Participants who have received only one prior line of immuno oncology (IO) based
regimen and have progressed on or after prior treatment with IO based regimen, or IO
ineligible participants who have received no prior systemic therapy. Participants
who previously received lenvatinib treatment are ineligible
11. For CRC Subpart in Expansion Part only: participants must have received at least 2
prior regimens (not exceeding 4 prior regimens) or could not tolerate standard
treatment and must have received the following prior therapies in the metastatic
setting if approved and locally available (progressed on at least 1 prior regimen in
the metastatic setting or could not tolerate standard treatment):
Note: Adjuvant chemotherapy counts as prior systemic treatment if there is
documented disease progression within 6 months of treatment completion Note: If a
participant is determined to be intolerant to prior standard treatment, the
participant must have received at least of 2 cycles of that therapy Note:
Participants who have received oral tyrosine kinase inhibitor (example, regorafenib)
are ineligible
1. Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular
endothelial growth factor (VEGF) monoclonal antibody (mAb) (example,
bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidine
in prior treatment Note: Participants who have previously received
fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only
chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after
discussion with the Sponsor
2. Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab
or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat
sarcoma viral oncogene homolog [KRAS)/ NRAS]) wild type (WT) CRC Note: RAS
(KRAS/NRAS) WT participants with right or left CRC lesions who may have not
been treated with anti-EGFR mAb based on local guidelines are eligible
3. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E
mutated tumors
4. Immune checkpoint inhibitor for participants with microsatellite
instability-high (MSI-H) CRC
12. For EC Subpart in Expansion Part only: Participants must have EC that has progressed
after prior platinum-based chemotherapy and an anti-programmed cell death (ligand) 1
(PD-[L])1)-directed therapy for EC (participants ineligible for IO therapy who have
progressed after prior platinum-based chemotherapy are eligible). Up to 3 prior
systemic therapies, of which up to 2 for metastatic or locally advanced disease, are
permitted Note: There is no restriction regarding prior hormonal therapies For Dose
Optimization Part only: Participants must have EC that has progressed after prior
platinum-based chemotherapy and an anti-PD-(L)1-directed therapy for EC. Up to 3
lines of prior therapy, regardless of setting, are allowed. Note: Prior hormonal
therapy and radiation are allowed and do not count as prior lines of therapy.
1. Any of cardiac conditions as follows:
- Heart failure New York Heart Association (NYHA) Class II or above
- Prolongation of QT interval with Fridericias correction (QTcF) to greater than
(>) 480 millisecond (msec)
- Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%)
2. Major surgery within 21 days or minor surgery (that is, simple excision) within 7
days prior to starting study drug. Participant must have recovered from the surgery
related toxicities to less than Grade 2 Note: Adequate wound healing after major
surgery must be assessed clinically, independent of time elapsed for eligibility
3. Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has
evaluated whether to include participant with HIV. Given that this is the first
combination study of E7386 with lenvatinib and that the main mechanism of action of
E7386 is immunomodulation of the tumor microenvironment along with the fact that
several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A
(CYP3A) substrates, the sponsor has decided not to include these participants at the
current time. However, further considerations will be made moving forward based on
new emerging data Note: HIV testing is required at screening only when mandated by
local health authority
4. Participants with proteinuria on urine dipstick testing will undergo 24-hour urine
collection for quantitative assessment of proteinuria. Participants with urine
protein >=1 gram per 24 hour will be ineligible
5. Active infection requiring systemic treatment (Except for Hepatitis B and/or C
[HBV/HCV] infection in HCC participants)
In case of HBsAg (+) participants in HCC participants:
- Antiviral therapy for HBV is not ongoing
- HBV viral load is 2000 international unit per milliliter (IU/mL) or more at the
Screening Period although antiviral therapy for HBV is ongoing
- Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleic
acid [DNA]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleic
acid [RNA]) at study entry
6. Diagnosed with meningeal carcinomatosis
7. Participants with central nervous system metastases are only eligible if they have
been previously treated and are radiologically stable, (that is, without evidence of
progression for at least 4 weeks prior to first dose of study treatment by repeat
imaging), clinically stable, and without requirement of steroid treatment for at
least 14 days prior to first dose of study treatment
8. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring
active treatment, including the use of oxygen
9. Any of bone disease/conditions as follows:
- T-score of < minus (-) 3.0 at the left or right total hip, left or right
femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray
absorptiometry (DXA) scan. Participants with T-score <-2.5 to -3.0 can only be
included if treatment with a bisphosphonate (example, zoledronic acid) or
denosumab has been started at least 14 days and no more than 6 months prior to
the first dose of study drug
- Metabolic bone disease, such as hyperparathyroidism, Paget's disease or
osteomalacia
- Symptomatic hypercalcemia requiring bisphosphonate therapy
- History of any fracture within 6 months prior to starting study drug
- Bone metastasis requiring orthopedic intervention
- Bone metastasis not being treated by bisphosphonate or denosumab. Participants
may be included if treatment with bisphosphonate or denosumab has been started
at least 14 days prior to the first dose of study drug. Participants with
previous solitary bone lesions controlled with radiotherapy are eligible
- History of symptomatic vertebral fragility fracture or any fragility fracture
of the hip, pelvis, wrist or other location (defined as any fracture without a
history of trauma or because of a fall from standing height or less)
- Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40%
decrease in the height of any vertebrae) morphometric vertebral fracture at
baseline
10. History of malignancy (except for original disease, or definitively treated melanoma
in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ [example,
bladder or cervix]) within the past 24 months prior to the first dose of study drug
11. For HCC Subpart in Dose Escalation Part only: Participants who experienced
discontinuation of lenvatinib, 2 or more dose reductions of lenvatinib required from
initial dose level of this study due to its toxicity, or participants who
experienced single dose reduction or consecutive >=8 days dose interruption of
lenvatinib within 60 days from the first dose, due to its toxicity. HCC Subpart in
Expansion Part only: Participants who previously received lenvatinib treatment are
ineligible.
EC Subpart in Expansion Part only: Participants previously treated with lenvatinib
who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to
less than 10 mg of lenvatinib due to toxicity within 60 days from the first dose.
EC Dose Optimization Part only: Participants who previously received lenvatinib
treatment are ineligible.
12. Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic
International Normalized Ratio (INR) monitoring for HCC participants only (example,
warfarin or similar agents). Treatment with low molecular weight heparin and factor
X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC
participants in Dose Escalation Part only
13. Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least
0.5 teaspoon) within 3 weeks prior to the first dose of study drug
14. For HCC participants only: History of hepatic encephalopathy within 6 months prior
to starting study drug
15. For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma
(malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial
stromal sarcomas
16. Has preexisting >=Grade 3 gastrointestinal or non-gastrointestinal fistula
17. Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing
unrecovered active sequelae of COVID-19 infection
18. Males who have not had a successful vasectomy (confirmed azoospermia) if their
female partners meet the exclusion criteria above (that is, the female partners are
of childbearing potential and are not willing to use a highly effective
contraceptive method throughout the study period and after study drug
discontinuation). No sperm donation is allowed during the study period and after
study drug discontinuation
19. Has a known psychiatric or substance abuse disorder that would interfere with the
participant ability to cooperate with the requirements of the study
20. Evidence of clinically significant disease (example, cardiac, respiratory,
gastrointestinal, renal disease) that in the opinion of the investigator could
affect the participant safety or interfere with the study assessments
21. Scheduled for major surgery during the study