Informations générales (source: ClinicalTrials.gov)
Dose Escalation, First-in-human Clinical Trial to Evaluate the Safety, Pharmacokinetics and Preliminary Antitumor Activity of PEP-010, Administered as Single Agent and in Combination With Paclitaxel or With Gemcitabine in Patients With Metastatic Solid Cancer
Interventional
Early Phase 1
Institut Curie (Voir sur ClinicalTrials)
mai 2021
décembre 2024
29 juin 2024
This is an open-label, non-controlled, multicenter, dose escalation, first-in-human phase
I clinical trial with an expansion phase designed to assess the safety, tolerability, PK
and PD parameters, and preliminary antitumor activity of intravenous dosing of PEP-010 as
single agent and in combination with paclitaxel or with gemcitabine
PEP-010 will be administered, in a Part 1, as single agent in patients with solid cancers
who are not amenable to standard treatment, or in combination in patients who are
eligible for the paclitaxel therapy, and in a Part 2 only in combination in:
Cohort 1 (expansion cohort, phase 1b): metastatic pancreatic ductal carcinoma (PDAC) who
received at least one previous systemic chemotherapy and eligible for paclitaxel therapy.
Cohort 2 (dose escalation cohort, phase 1a): metastatic pancreatic ductal carcinoma or
advanced/metastatic ovarian cancer (OC) eligible for gemcitabine-based therapy
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/09/2024 13:49:44 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Sophie POSTEL-VINAY | 17/05/2024 14:05:38 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| CLCC F.Baclesse Caen - Caen - France | COQUAN, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancerologie de l'Ouest- ICO - 44805 - Saint-Herblain - France | HIRET, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion criteria:
Part 1 Arms A and B:
1. Arm A: Patients must have histologically confirmed diagnosis of recurrent and/or
metastatic solid tumors, who are not amenable to standard therapy, with exceptions
as defined in the non-inclusion criteria,
2. Arm B: Patients must have histologically confirmed diagnosis of recurrent and/or
metastatic solid tumors. Patients must be eligible for a treatment with paclitaxel
as single agent. Patients who are eligible for standard of care paclitaxel-based
combination therapy should not be included in the trial unless they have been
previously exposed to that specific combination therapy. Specifically :
- Patients with ovarian cancer must have received prior therapy with paclitaxel
as part of standard of care in combination with carboplatin.
- Patients with triple negative breast cancer are eligible for the trial since
paclitaxel as single agent is standard of care in this disease.
3. Age ≥ 18 years,
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
5. Patients must have measurable disease (as per RECIST version 1.1),
6. Patient ability to comply with the collection of tumor biopsies, and tumors must be
accessible for biopsy,
7. Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥
1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
8. Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit
of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
9. Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
10. Provision of signed written informed consent,
11. Patient ability to comply with protocol requirements,
12. If the patient is female:
- Patient must be postmenopausal, surgically sterile, or they must agree to use a
physical barrier method of contraception in addition to either an intrauterine
device or hormonal contraception until at least 6 months after termination of
study drug or must refrain from heterosexual activity during this same period.
- Patients of childbearing potential must have a negative pregnancy test within
the seven days prior to the first study drug administration.
If the patient is male:
- Patient must abstain from heterosexual activity or must agree to use an
acceptable method of contraception (e.g., condom) during the study for at least
6 months after termination of study drug.
13. Patients covered by a health insurance system; Part 2 Cohort 1 Pancreatic Ductal
adenocarcinoma (PDAC)
1. Age ≥ 18 years,
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
3. Patients must have measurable disease (as per RECIST version 1.1),
4. Patient ability to comply with the collection of tumor biopsies, and tumors must be
accessible for biopsy,
5. Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥
1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
6. Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit
of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
7. Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
8. Provision of signed written informed consent,
9. Patient ability to comply with protocol requirements,
10. If the patient is female:
- Patient must be postmenopausal, surgically sterile, or they must agree to use a
physical barrier method of contraception in addition to either an intrauterine
device or hormonal contraception until at least 6 months after termination of
study drug or must refrain from heterosexual activity during this same period.
- Patients of childbearing potential must have a negative pregnancy test within
the seven days prior to the first study drug administration.
If the patient is male:
- Patient must abstain from heterosexual activity or must agree to use an
acceptable method of contraception (e.g., condom) during the study for at least
6 months after termination of study drug.
11. Patients covered by a health insurance system
12. Histologically confirmed metastatic pancreatic ductal adenocarcinoma (mixed
histology is acceptable as long adenocarcinoma is the dominant histological subtype)
13. Patient should have received at least one previous line of systemic treatment in
metastatic setting
14. No previous disease progression under taxane therapy or 12-month free interval since
last taxane therapy.
Part 2 Cohort 2 Pancreatic Ductal adenocarcinoma (PDAC) or Ovarian Cancer (OC)
1. Age ≥ 18 years,
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
3. Patients must have measurable disease (as per RECIST version 1.1),
4. Patient ability to comply with the collection of tumor biopsies, and tumors must be
accessible for biopsy,
5. Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥
1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
6. Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit
of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
7. Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
8. Provision of signed written informed consent,
9. Patient ability to comply with protocol requirements,
10. If the patient is female:
- Patient must be postmenopausal, surgically sterile, or they must agree to use a
physical barrier method of contraception in addition to either an intrauterine
device or hormonal contraception until at least 6 months after termination of
study drug or must refrain from heterosexual activity during this same period.
- Patients of childbearing potential must have a negative pregnancy test within
the seven days prior to the first study drug administration.
If the patient is male:
- Patient must abstain from heterosexual activity or must agree to use an
acceptable method of contraception (e.g., condom) during the study for at least
6 months after termination of study drug.
11. Patients covered by a health insurance system
12. Patient must be eligible for gemcitabine-based treatment.
Specific Pancreatic Ductal adenocarcinoma (PDAC) 13. Histologically confirmed metastatic
pancreatic ductal adenocarcinoma (mixed histology is acceptable as long adenocarcinoma is
the dominant histological subtype) 14. Patient not eligible for other treatment than
gemcitabine monotherapy as first line metastatic treatment Specific ovarian cancer (OC)
15. Patient has been diagnosed with recurrent epithelial ovarian, peritoneal, or
fallopian tube carcinoma.
16. Subjects had disease recurrence or progression during prior chemotherapy with
platinum-based regimens or within 6 months after the last dose of chemotherapy with
platinum-based regimens (for at least 4 cycles of treatment) 17. Patient should have
received at least one previous line of treatment in platinum-resistant setting,
excluding gemcitabine-based regimen Non-inclusion criteria: Part 1 Arms A and B,
Part 2 Cohorts 1 and 2
1. Arm B and Cohort 1: Allergy or hypersensitivity to paclitaxel or components of the
paclitaxel formulation,
2. Cohort 2: Allergy or hypersensitivity to gemcitabine or components of the
gemcitabine formulation,
3. Allergy or hypersensitivity to PEP-010 formulation (Trehalose, Tween 20),
4. Patients with known or suspected Central Nervous System (CNS) metastases including
leptomeningeal metastasis (except patients with radiographically stable,
asymptomatic previously irradiated lesion provided patient is ≥ 3 weeks beyond
completing cranial irradiation),
5. Evidence of significant, uncontrolled concomitant diseases, which could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (such as New York Heart Association Class III or IV cardiac
disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
unstable angina), or pulmonary disease (including obstructive pulmonary disease and
history of symptomatic bronchospasm),
6. Concomitant cancer in the past 3 years except prostate cancer controlled by hormone
therapy, cutaneous cancers (except melanoma) and in situ carcinoma,
7. Prior chemotherapy, radiotherapy (other than short cycle of palliative
radiotherapy), immunotherapy within 21 days of first receipt of study drug,
8. Prior investigational agent within 28 days of first PEP-010 administration,
9. Hormone therapy within 14 days of first receipt of study drug, with exception of
Gonadotropin-Releasing Hormone (GnRH) or Luteinizing-Hormone-Releasing Hormone
(LHRH) agonists used for advanced prostate cancer, if indicated,
10. Prior relevant toxicities from chemotherapy or radiotherapy which have not regressed
to grade ≤1 severity except alopecia (NCI-CTCAE version 5.0),
11. Patients with acute infection.
12. Any other uncontrolled diseases, metabolic dysfunction, physical examination
finding, or clinical laboratory finding or any other medical condition that, in the
opinion of the investigator, contraindicates the use of an investigational drug, or
will impose excessive risk to the patient,
13. Patients with known HIV, HBV and HCV infections,
14. Patients with known Sars Cov 2 infection
15. Pregnant or lactating women,
16. Patients with altered mental status or psychiatric disorder that, in the opinion of
the investigator, would preclude a valid patient informed consent,
17. Person deprived of liberty or under guardianship.
Part 1 Arms A and B:
1. Arm A: Patients must have histologically confirmed diagnosis of recurrent and/or
metastatic solid tumors, who are not amenable to standard therapy, with exceptions
as defined in the non-inclusion criteria,
2. Arm B: Patients must have histologically confirmed diagnosis of recurrent and/or
metastatic solid tumors. Patients must be eligible for a treatment with paclitaxel
as single agent. Patients who are eligible for standard of care paclitaxel-based
combination therapy should not be included in the trial unless they have been
previously exposed to that specific combination therapy. Specifically :
- Patients with ovarian cancer must have received prior therapy with paclitaxel
as part of standard of care in combination with carboplatin.
- Patients with triple negative breast cancer are eligible for the trial since
paclitaxel as single agent is standard of care in this disease.
3. Age ≥ 18 years,
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
5. Patients must have measurable disease (as per RECIST version 1.1),
6. Patient ability to comply with the collection of tumor biopsies, and tumors must be
accessible for biopsy,
7. Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥
1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
8. Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit
of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
9. Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
10. Provision of signed written informed consent,
11. Patient ability to comply with protocol requirements,
12. If the patient is female:
- Patient must be postmenopausal, surgically sterile, or they must agree to use a
physical barrier method of contraception in addition to either an intrauterine
device or hormonal contraception until at least 6 months after termination of
study drug or must refrain from heterosexual activity during this same period.
- Patients of childbearing potential must have a negative pregnancy test within
the seven days prior to the first study drug administration.
If the patient is male:
- Patient must abstain from heterosexual activity or must agree to use an
acceptable method of contraception (e.g., condom) during the study for at least
6 months after termination of study drug.
13. Patients covered by a health insurance system; Part 2 Cohort 1 Pancreatic Ductal
adenocarcinoma (PDAC)
1. Age ≥ 18 years,
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
3. Patients must have measurable disease (as per RECIST version 1.1),
4. Patient ability to comply with the collection of tumor biopsies, and tumors must be
accessible for biopsy,
5. Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥
1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
6. Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit
of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
7. Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
8. Provision of signed written informed consent,
9. Patient ability to comply with protocol requirements,
10. If the patient is female:
- Patient must be postmenopausal, surgically sterile, or they must agree to use a
physical barrier method of contraception in addition to either an intrauterine
device or hormonal contraception until at least 6 months after termination of
study drug or must refrain from heterosexual activity during this same period.
- Patients of childbearing potential must have a negative pregnancy test within
the seven days prior to the first study drug administration.
If the patient is male:
- Patient must abstain from heterosexual activity or must agree to use an
acceptable method of contraception (e.g., condom) during the study for at least
6 months after termination of study drug.
11. Patients covered by a health insurance system
12. Histologically confirmed metastatic pancreatic ductal adenocarcinoma (mixed
histology is acceptable as long adenocarcinoma is the dominant histological subtype)
13. Patient should have received at least one previous line of systemic treatment in
metastatic setting
14. No previous disease progression under taxane therapy or 12-month free interval since
last taxane therapy.
Part 2 Cohort 2 Pancreatic Ductal adenocarcinoma (PDAC) or Ovarian Cancer (OC)
1. Age ≥ 18 years,
2. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1,
3. Patients must have measurable disease (as per RECIST version 1.1),
4. Patient ability to comply with the collection of tumor biopsies, and tumors must be
accessible for biopsy,
5. Adequate bone marrow function as defined by: Absolute Neutrophil Count (ANC) of ≥
1.5 x 109/L, platelet count of ≥ 100 x 109/L, and hemoglobin of ≥ 9 g/dL),
6. Adequate liver function, as determined by a serum total bilirubin ≤ 1.5 Upper Limit
of Normal (ULN), AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver metastases),
7. Adequate renal function, as determined by a serum creatinine ≤ 1.5 x ULN,
8. Provision of signed written informed consent,
9. Patient ability to comply with protocol requirements,
10. If the patient is female:
- Patient must be postmenopausal, surgically sterile, or they must agree to use a
physical barrier method of contraception in addition to either an intrauterine
device or hormonal contraception until at least 6 months after termination of
study drug or must refrain from heterosexual activity during this same period.
- Patients of childbearing potential must have a negative pregnancy test within
the seven days prior to the first study drug administration.
If the patient is male:
- Patient must abstain from heterosexual activity or must agree to use an
acceptable method of contraception (e.g., condom) during the study for at least
6 months after termination of study drug.
11. Patients covered by a health insurance system
12. Patient must be eligible for gemcitabine-based treatment.
Specific Pancreatic Ductal adenocarcinoma (PDAC) 13. Histologically confirmed metastatic
pancreatic ductal adenocarcinoma (mixed histology is acceptable as long adenocarcinoma is
the dominant histological subtype) 14. Patient not eligible for other treatment than
gemcitabine monotherapy as first line metastatic treatment Specific ovarian cancer (OC)
15. Patient has been diagnosed with recurrent epithelial ovarian, peritoneal, or
fallopian tube carcinoma.
16. Subjects had disease recurrence or progression during prior chemotherapy with
platinum-based regimens or within 6 months after the last dose of chemotherapy with
platinum-based regimens (for at least 4 cycles of treatment) 17. Patient should have
received at least one previous line of treatment in platinum-resistant setting,
excluding gemcitabine-based regimen Non-inclusion criteria: Part 1 Arms A and B,
Part 2 Cohorts 1 and 2
1. Arm B and Cohort 1: Allergy or hypersensitivity to paclitaxel or components of the
paclitaxel formulation,
2. Cohort 2: Allergy or hypersensitivity to gemcitabine or components of the
gemcitabine formulation,
3. Allergy or hypersensitivity to PEP-010 formulation (Trehalose, Tween 20),
4. Patients with known or suspected Central Nervous System (CNS) metastases including
leptomeningeal metastasis (except patients with radiographically stable,
asymptomatic previously irradiated lesion provided patient is ≥ 3 weeks beyond
completing cranial irradiation),
5. Evidence of significant, uncontrolled concomitant diseases, which could affect
compliance with the protocol or interpretation of results, including significant
cardiovascular disease (such as New York Heart Association Class III or IV cardiac
disease, myocardial infarction within the last 6 months, unstable arrhythmias, or
unstable angina), or pulmonary disease (including obstructive pulmonary disease and
history of symptomatic bronchospasm),
6. Concomitant cancer in the past 3 years except prostate cancer controlled by hormone
therapy, cutaneous cancers (except melanoma) and in situ carcinoma,
7. Prior chemotherapy, radiotherapy (other than short cycle of palliative
radiotherapy), immunotherapy within 21 days of first receipt of study drug,
8. Prior investigational agent within 28 days of first PEP-010 administration,
9. Hormone therapy within 14 days of first receipt of study drug, with exception of
Gonadotropin-Releasing Hormone (GnRH) or Luteinizing-Hormone-Releasing Hormone
(LHRH) agonists used for advanced prostate cancer, if indicated,
10. Prior relevant toxicities from chemotherapy or radiotherapy which have not regressed
to grade ≤1 severity except alopecia (NCI-CTCAE version 5.0),
11. Patients with acute infection.
12. Any other uncontrolled diseases, metabolic dysfunction, physical examination
finding, or clinical laboratory finding or any other medical condition that, in the
opinion of the investigator, contraindicates the use of an investigational drug, or
will impose excessive risk to the patient,
13. Patients with known HIV, HBV and HCV infections,
14. Patients with known Sars Cov 2 infection
15. Pregnant or lactating women,
16. Patients with altered mental status or psychiatric disorder that, in the opinion of
the investigator, would preclude a valid patient informed consent,
17. Person deprived of liberty or under guardianship.