Clinical Trials List
Protocol NumberB9991010
NCT Number(ClinicalTrials.gov Identfier)NCT02718417
2016-07-01 - 2019-12-24
Phase III
Terminated7
ICD-10C56
Malignant neoplasm of ovary
ICD-9183.0
Malignant neoplasm of ovary
A RANDOMIZED, OPEN-LABEL, MULTICENTER, PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AND/OR FOLLOWING CHEMOTHERAPY IN PATIENTS WITH PREVIOUSLY UNTREATED EPITHELIAL OVARIAN CANCER
-
Trial Applicant
Syneos Health
-
Sponsor
Pfizer, Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chi-Mu Chuang Division of Obstetrics & Gynecology
- Huann-Cheng Horng Division of Obstetrics & Gynecology
- 吳華席 Division of Obstetrics & Gynecology
- Yi-Jen Chen Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
9 Stop recruiting
Audit
None
Co-Principal Investigator
- 黃家彥 Division of Obstetrics & Gynecology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- 陳鵬宇 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wen-Fang Cheng Division of Obstetrics & Gynecology
- YING-CHENG CHIANG Division of Obstetrics & Gynecology
- CHI-HAU CHEN CHI-HAU CHEN Division of Obstetrics & Gynecology
- 童寶玲 Division of Obstetrics & Gynecology
- 施怡倫 Division of Radiology
- 毛翠蓮 Division of Others
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chyong-Huey Lai 無
- Huei-Jean Huang 無
- 周宏學 無
- Min-Yu Chen 無
- Cheng-Tao Lin 無
- 邱健泰 無
- 黃寬仁 無
- Angel Chao 無
The Actual Total Number of Participants Enrolled
0 Stop recruiting
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Epithelial Ovarian Cancer
Objectives
Co-Primary Objectives:
1. To demonstrate that avelumab in combination with platinum-based chemotherapy
followed by avelumab maintenance (Arm C) is superior to platinum-based
chemotherapy alone followed by observation (Arm A) in prolonging progression free
survival (PFS) in patients with previously untreated epithelial ovarian cancer (EOC).
2. To demonstrate that platinum-based chemotherapy alone followed by avelumab
maintenance (Arm B) is superior to platinum-based chemotherapy alone followed by
observation (Arm A) in prolonging PFS in patients with previously untreated EOC.
Test Drug
MSB0010718C 20mg/ml Solution for Infusion
Active Ingredient
Avelumab (MSB0010718C)
Dosage Form
Solution for Infusion
Dosage
10ml
Endpoints
Primary Endpoint
Progression-free survival (PFS) as determined by blinded independent central review
(BICR) by RECIST version 1.1
Secondary Endpoints
Efficacy: Overall survival (OS), PFS by Investigator assessment as well as Objective
response (OR), Duration of response (DR), Maintenance PFS by BICR assessments
and Investigator assessment, pathological Complete Response (pCR), PFS2, and PFS
by Gynecological Cancer Intergroup (GCIG) criteria
Safety: AEs (as graded by NCI CTCAE v.4.03); laboratory abnormalities (as graded
by NCI CTCAE v.4.03); vital signs (blood pressure, pulse rate); electrocardiograms
(ECGs)
Patient-Reported Outcomes: FOSI-18 and EuroQoL5 Dimension (EQ-5D-5L)
Pharmacokinetics: PK parameters, including Ctrough, Cmax, volume of distribution (Vd),
clearance (CL), area under the concentration time curve (AUC) for avelumab,
paclitaxel, and carboplatin, as data permit
Immunogenicity: anti-drug antibodies (ADA) and neutralizing antibodies (Nab)
against avelumab
Candidate predictive biomarkers in tumor tissue including, but not limited to,
PD-L1 expression and tumor infiltrating CD8+ T lymphocytes as assessed by
immunohistochemistry (IHC)
Exploratory Endpoints
Pre- and post-dose levels of cells, deoxyribonucleic acid (DNA), ribonucleic acid
(RNA), or proteins from tumor specimen and/or blood that are related to immune
response, response to, or disease progression on avelumab, such as levels of IL-8 and
IFN in blood and/or tissue, expression of FoxP3, PD-1, and PD-L2, homologous
recombination deficiency testing on tumor tissue
CA-125 levels
ir (immune-related) PFS, irOR, and irDR per irRECIST (see Appendix 4)
Progression-free survival (PFS) as determined by blinded independent central review
(BICR) by RECIST version 1.1
Secondary Endpoints
Efficacy: Overall survival (OS), PFS by Investigator assessment as well as Objective
response (OR), Duration of response (DR), Maintenance PFS by BICR assessments
and Investigator assessment, pathological Complete Response (pCR), PFS2, and PFS
by Gynecological Cancer Intergroup (GCIG) criteria
Safety: AEs (as graded by NCI CTCAE v.4.03); laboratory abnormalities (as graded
by NCI CTCAE v.4.03); vital signs (blood pressure, pulse rate); electrocardiograms
(ECGs)
Patient-Reported Outcomes: FOSI-18 and EuroQoL5 Dimension (EQ-5D-5L)
Pharmacokinetics: PK parameters, including Ctrough, Cmax, volume of distribution (Vd),
clearance (CL), area under the concentration time curve (AUC) for avelumab,
paclitaxel, and carboplatin, as data permit
Immunogenicity: anti-drug antibodies (ADA) and neutralizing antibodies (Nab)
against avelumab
Candidate predictive biomarkers in tumor tissue including, but not limited to,
PD-L1 expression and tumor infiltrating CD8+ T lymphocytes as assessed by
immunohistochemistry (IHC)
Exploratory Endpoints
Pre- and post-dose levels of cells, deoxyribonucleic acid (DNA), ribonucleic acid
(RNA), or proteins from tumor specimen and/or blood that are related to immune
response, response to, or disease progression on avelumab, such as levels of IL-8 and
IFN in blood and/or tissue, expression of FoxP3, PD-1, and PD-L2, homologous
recombination deficiency testing on tumor tissue
CA-125 levels
ir (immune-related) PFS, irOR, and irDR per irRECIST (see Appendix 4)
Inclution Criteria
Inclusion Criteria
Patient eligibility should be reviewed and documented by an appropriate member of the
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary
peritoneal cancer (according to AJCC/UICC TNM and International Federation of
Gynecology and Obstetrics (FIGO) Staging System 2014 edition), including malignant
mixed Müllerian tumors with high grade serous component.38
2. Patients must be candidates for platinum based chemotherapy and previously untreated.
3. Patients must have completed a surgical debulking procedure, or be candidates for
neoadjuvant chemotherapy.
a. For patients enrolling after debulking surgery, the following conditions must be met:
The minimum surgery required is an abdominal surgery with an attempt at
cytoreduction providing tissue for histologic evaluation and establishing and
documenting the primary site and stage
Patient must be randomized at a maximum of 8 weeks after surgery.
b. For patients who are candidates for neoadjuvant chemotherapy, the following
conditions must be met:
A core tissue (not fine needle aspiration) biopsy is required. The tissue must be
consistent with a tumor of Müllerian origin.
Stage IIIC–IV documented via imaging or surgery (without attempt at
cytoreduction)
Serum CA125/ CEA ratio > 25. If the serum CA125/CEA ratio is < 25, workup
should be negative for the presence of a primary gastrointestinal or breast
malignancy (< 6 weeks before randomization).
Plan to receive carboplatin-paclitaxel neoadjuvant chemotherapy.
Randomization must occur within 8 weeks after diagnosis.
4. Availability of an archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue block
or a minimum of 15 slides. If archived FFPE tissue is not available, a de novo (ie, fresh)
tumor sample must be obtained in accordance with local institutional practice for tumor
biopsies.
5. Eastern Cooperative Group (ECOG) performance status 0-1 (see Appendix 2).
6. Age 18 years (or 20 years in Japan).
7. Adequate hematological function (ANC 1.5 x 109
/L, Hgb 9.0 g/dL, and platelet count
100 x 109
/L).
8. Adequate liver function tests (ALT/AST 2.5 x ULN, total serum bilirubin level 1.5 x
ULN).
9. Adequate renal function by estimated creatinine clearance 50 mL/min as calculated
using the Cockcroft-Gault method.
10. Estimated life expectancy of at least 12 weeks.
11. Evidence of a personally signed and dated informed consent document indicating that the
patient (or a legally acceptable representative) has been informed of all pertinent aspects
of the study.
12. Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
13. Patients of childbearing potential and at risk for pregnancy must agree to use 2 highly
effective methods of contraception throughout the study and for at least 60 days after the
last dose of assigned treatment.
Patients of non-childbearing potential must meet at least one of the following criteria:
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses for
at least 12 consecutive months with no alternative pathological or physiological cause;
status may be confirmed by having a serum follicle-stimulating hormone (FSH) level
confirming the post-menopausal state.
All other patients (including patients with tubal ligations) will be considered to be of
childbearing potential.
Patient eligibility should be reviewed and documented by an appropriate member of the
investigator’s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the
study:
1. Histologically confirmed Stage III-IV epithelial ovarian, fallopian tube, or primary
peritoneal cancer (according to AJCC/UICC TNM and International Federation of
Gynecology and Obstetrics (FIGO) Staging System 2014 edition), including malignant
mixed Müllerian tumors with high grade serous component.38
2. Patients must be candidates for platinum based chemotherapy and previously untreated.
3. Patients must have completed a surgical debulking procedure, or be candidates for
neoadjuvant chemotherapy.
a. For patients enrolling after debulking surgery, the following conditions must be met:
The minimum surgery required is an abdominal surgery with an attempt at
cytoreduction providing tissue for histologic evaluation and establishing and
documenting the primary site and stage
Patient must be randomized at a maximum of 8 weeks after surgery.
b. For patients who are candidates for neoadjuvant chemotherapy, the following
conditions must be met:
A core tissue (not fine needle aspiration) biopsy is required. The tissue must be
consistent with a tumor of Müllerian origin.
Stage IIIC–IV documented via imaging or surgery (without attempt at
cytoreduction)
Serum CA125/ CEA ratio > 25. If the serum CA125/CEA ratio is < 25, workup
should be negative for the presence of a primary gastrointestinal or breast
malignancy (< 6 weeks before randomization).
Plan to receive carboplatin-paclitaxel neoadjuvant chemotherapy.
Randomization must occur within 8 weeks after diagnosis.
4. Availability of an archival formalin-fixed, paraffin-embedded (FFPE) tumor tissue block
or a minimum of 15 slides. If archived FFPE tissue is not available, a de novo (ie, fresh)
tumor sample must be obtained in accordance with local institutional practice for tumor
biopsies.
5. Eastern Cooperative Group (ECOG) performance status 0-1 (see Appendix 2).
6. Age 18 years (or 20 years in Japan).
7. Adequate hematological function (ANC 1.5 x 109
/L, Hgb 9.0 g/dL, and platelet count
100 x 109
/L).
8. Adequate liver function tests (ALT/AST 2.5 x ULN, total serum bilirubin level 1.5 x
ULN).
9. Adequate renal function by estimated creatinine clearance 50 mL/min as calculated
using the Cockcroft-Gault method.
10. Estimated life expectancy of at least 12 weeks.
11. Evidence of a personally signed and dated informed consent document indicating that the
patient (or a legally acceptable representative) has been informed of all pertinent aspects
of the study.
12. Patients who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
13. Patients of childbearing potential and at risk for pregnancy must agree to use 2 highly
effective methods of contraception throughout the study and for at least 60 days after the
last dose of assigned treatment.
Patients of non-childbearing potential must meet at least one of the following criteria:
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure; or
Achieved postmenopausal status, defined as follows: cessation of regular menses for
at least 12 consecutive months with no alternative pathological or physiological cause;
status may be confirmed by having a serum follicle-stimulating hormone (FSH) level
confirming the post-menopausal state.
All other patients (including patients with tubal ligations) will be considered to be of
childbearing potential.
Exclusion Criteria
Exclusion Criteria
Patients with any of the following characteristics/conditions will not be included in the study:
1. Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline
tumors).
2. Mucinous tumors.
3. Cancer for which intraperitoneal cytotoxic chemotherapy is planned.
4. Prior systemic anti-cancer treatment for EOC, FTC, or PPC.
5. Prior immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody
(including ipilimumab), or any other antibody or drug specifically targeting T cell co
stimulation or immune checkpoint pathways.
6. Major surgery (other than debulking surgery) for any reason within 4 weeks prior to
randomization and/or incomplete recovery from surgery.
7. Known brain, leptomeningeal, or spinal cord metastases.
8. Current or prior use of immunosuppressive medication within 7 days prior to
randomization, except the following: intranasal, inhaled, topical steroids, or local steroid
injections (eg, intra-articular injection); systemic corticosteroids at physiologic doses
10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity
reactions [eg, computed tomography (CT) scan premedication].
9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agents except patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism
not requiring immunosuppressive treatment.
10. Any of the following in the previous 6 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic
pulmonary embolism.
11. Active and clinically significant bacterial, fungal or viral infection, any positive tests for
hepatitis B (HBV), hepatitis C (HCV) indicating acute or chronic infection, known
human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)
related illness.
12. Administration of a live vaccine within 30 days prior to study entry.
13. Known severe hypersensitivity reactions to monoclonal antibodies, carboplatin, or
paclitaxel (NCI CTCAE v4.03 Grade 3), any history of anaphylaxis, or uncontrolled
asthma (ie, 3 or more features of partially controlled asthma).39
14. Persisting NCI CTCAE v4.03 Grade >1 toxicity related to prior therapy.
15. Previous malignant disease other than the target malignancy to be investigated in this trial
within the last 5 years with the exception of adequately treated basal or squamous cell
carcinoma of the skin, cervical carcinoma in situ, lobular carcinoma in situ (LCIS), or
ductal carcinoma in situ (DCIS).
16. Patients who are investigational site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees directly involved in the conduct of the
study.
17. Participation in other clinical studies involving investigational drug(s) within 4 weeks
prior to study randomization and/or during study participation.
18. Other severe/severe acute or chronic medical, including colitis, inflammatory bowel
disease, and pneumonitis, or psychiatric condition, including recent (within the past year)
or active suicidal ideation or behavior) or laboratory abnormality that may increase the
risk associated with study participation or investigational product administration or may
interfere with the interpretation of study results and, in the judgment of the investigator,
would make the patient inappropriate for entry into this study.
19. Pregnant patients or breastfeeding patients.
Patients with any of the following characteristics/conditions will not be included in the study:
1. Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline
tumors).
2. Mucinous tumors.
3. Cancer for which intraperitoneal cytotoxic chemotherapy is planned.
4. Prior systemic anti-cancer treatment for EOC, FTC, or PPC.
5. Prior immunotherapy with IL-2, IFN-α, or anti-PD-1, anti-PD-L1, anti-PD-L2,
anti-CD137, or anti-cytotoxic T lymphocyte associated antigen 4 (anti-CTLA-4) antibody
(including ipilimumab), or any other antibody or drug specifically targeting T cell co
stimulation or immune checkpoint pathways.
6. Major surgery (other than debulking surgery) for any reason within 4 weeks prior to
randomization and/or incomplete recovery from surgery.
7. Known brain, leptomeningeal, or spinal cord metastases.
8. Current or prior use of immunosuppressive medication within 7 days prior to
randomization, except the following: intranasal, inhaled, topical steroids, or local steroid
injections (eg, intra-articular injection); systemic corticosteroids at physiologic doses
10 mg/day of prednisone or equivalent; steroids as premedication for hypersensitivity
reactions [eg, computed tomography (CT) scan premedication].
9. Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agents except patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroidism
not requiring immunosuppressive treatment.
10. Any of the following in the previous 6 months: myocardial infarction, severe/unstable
angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure,
cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic
pulmonary embolism.
11. Active and clinically significant bacterial, fungal or viral infection, any positive tests for
hepatitis B (HBV), hepatitis C (HCV) indicating acute or chronic infection, known
human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)
related illness.
12. Administration of a live vaccine within 30 days prior to study entry.
13. Known severe hypersensitivity reactions to monoclonal antibodies, carboplatin, or
paclitaxel (NCI CTCAE v4.03 Grade 3), any history of anaphylaxis, or uncontrolled
asthma (ie, 3 or more features of partially controlled asthma).39
14. Persisting NCI CTCAE v4.03 Grade >1 toxicity related to prior therapy.
15. Previous malignant disease other than the target malignancy to be investigated in this trial
within the last 5 years with the exception of adequately treated basal or squamous cell
carcinoma of the skin, cervical carcinoma in situ, lobular carcinoma in situ (LCIS), or
ductal carcinoma in situ (DCIS).
16. Patients who are investigational site staff members directly involved in the conduct of the
study and their family members, site staff members otherwise supervised by the
investigator, or patients who are Pfizer employees directly involved in the conduct of the
study.
17. Participation in other clinical studies involving investigational drug(s) within 4 weeks
prior to study randomization and/or during study participation.
18. Other severe/severe acute or chronic medical, including colitis, inflammatory bowel
disease, and pneumonitis, or psychiatric condition, including recent (within the past year)
or active suicidal ideation or behavior) or laboratory abnormality that may increase the
risk associated with study participation or investigational product administration or may
interfere with the interpretation of study results and, in the judgment of the investigator,
would make the patient inappropriate for entry into this study.
19. Pregnant patients or breastfeeding patients.
The Estimated Number of Participants
-
Taiwan
42 participants
-
Global
951 participants
