Adjuvant Chemotherapy of Three-step Regimen in BRCA1/2 Wide Type Ovarian Cancer (ACTS-2)
Primary Purpose
Ovarian Cancer
Status
Recruiting
Phase
Phase 3
Locations
China
Study Type
Interventional
Intervention
Etoposide, Cyclophosphamide, Carboplatin/Cisplatin
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring adjuvent chemotherapy, ovarian cancer, maitainance therapy
Eligibility Criteria
Inclusion Criteria:
- Female patients 18-75 years of age.
- ECOG 0-2
- Histologically-confirmed epithelial ovarian or fallopian-tube cancer or primary peritoneal cancer
- FIGO2018 stage III/IV,
- Patients should have received optimal cytoreductive surgery with residual tumor ≤ 1cm and no more than 9 cycle paclitaxel + platinum chemotherapy achieved complete remission (accessed ) and normal CA125.
- No more than 8 months after the last chemotherapy.
- Adequate bone marrow and hepatic function at Screening:
- Hemoglobin ≥9 g/dL
- White blood cell count ≥3.0 × 109/L
- Absolute neutrophil count ≥1.5 × 109/L
- Platelet count ≥100 × 109/L
- AST (SGOT)/ALT (SGPT) ≤2.5 ULN
- Bilirubin <1.5 × ULN
- Creatinine <1.5 × ULN.
- Ability and willingness to give written informed consent.
- Tumor BRCA1/2 wilde type (qualified center test)
Exclusion Criteria:
- Primary or secondary immune deficiency.
- Any uncontrolled medical condition that may put the patient at high risk during treatment .
- Receipt of any other investigational medicinal product within the last 30 days before randomization.
- Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years.
- Severe heart/ lung/ liver/ kidney failure.
- uncontroled or active infection disease.
- Legal incompetence, limited legal competence, or detainment in an institution for official or legal reasons.
- Receipt of pelvic or abdominal radiotherapy
- Mucinous adenocarcinoma, low grade carcinoma
Sites / Locations
- Wu XiaohuaRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Follow-up
three steps chemotherapy
Arm Description
No interevention
Cyclophosphamide 400mg(250mg/m2)+Etoposide 100mg (70mg/m2)d1-d3 iv 4w/6cycles , followed by Carboplatin (AUC=5)+Cyclophosphamide 600mg(400mg/m2)d1-d2 iv 8w/6cycles.
Outcomes
Primary Outcome Measures
Progression-Free-Survival (PFS)
Secondary Outcome Measures
overall survival (OS)
Health-related quality of life questionnaire
Adverse Events (AE)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04520074
Brief Title
Adjuvant Chemotherapy of Three-step Regimen in BRCA1/2 Wide Type Ovarian Cancer (ACTS-2)
Official Title
A Phase III,Randomized, Multi-center, Open Label Study of Adjuvant Chemotherapy of Three-step Regimens (ACTS) in BRCA1/2 Wide-type Stage III and Stage IV Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (EOC, FTC, PPC)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 8, 2021 (Actual)
Primary Completion Date
September 2027 (Anticipated)
Study Completion Date
September 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Ovarian cancer was mostly diagnosed at late stage (III/IV) with high rate of recurrence after first line of therapy by optimal cytoreductive sugery and 6cycle of TP chemotherapy. There is no standard maintainance therapy for BRCA1/2 wide-type ovarian cancer. We developed an adjuvant chemotherapy of "three steps" (ACTS). It is adding CTX+VP-16(second step) 6cycle and CTX+CBP(third steps) to firstline chemotherapy (first step). The aim of this study is to verify the effectivity and safety of ACTS in BRCA1/2 wide-type ovarian cancer patients.
Detailed Description
More than 70 percent of ovarian cancer patients were diagnosed in the advanced stage. Currently the 5-year disease free survival (DFS) of stageⅢ-Ⅳovarian cancer patients was about 10 percent after first line chemotherapy. Dr Cai shumo developed adjuvant chemotherapy of "three steps" (ACTS) for advanced ovarian cancer after cytoreductive surgery, based on his 60+ years experience on gynecologic oncology. After the first step 6-8 cycle paclitaxel plus carboplatin chemotherapy, the chemo-sensative cancer cells were killed, but resistant/dormancy cell remained. The second step chemotherapy which is 6 cycle CTX+VP-16 every 4weeks, using different mechanism to kill cancer cells, may decrease the rate of recurrence within 6 month after first step chemotherapy, prolong platinum-free duration and also with acceptable side effects. After second step chemotherapy, in absence of 6 months platinum treatment, the previous G0 dormancy cell may become flexible to platinum treatment. Therefore, in the third step chemotherapy, CTX+CBP is used in every 8 week for 6 cycles. Comparing to using targeted therapy for maintaining therapy, the ACTS cost less.
In the previous observation study(CHINA ONCOLOGY 2013 Vol.23 No.12 p980), In study arm A, the patients received three-step chemotherapy after primary debulking surgery, step one with paclitaxel plus carboplatin (TC regimen), every 3 weeks for 6 to 8 cycles; step two with etoposide plus cyclophosphamide, every 4 weeks for 6 cycles; step three with carboplatin plus cyclophosphamide every eight weeks for six cycles. In control arm B, investigators retrospectively analysed 51 cases withⅢC-Ⅳstage ovarian cancer, who had completely response after standard chemotherapy with six to eight cycles of TC after primary surgery during 2007. Investigators compared the 5-year DFS between the two arms. Results: The 5-year DFS of 15 cases in arm A was 80%(12/15), which was signiifcantly higher than that of arm B (5.9%, 3/51, P<0.01). Therefore we start this randomized open control clinic trial to evaluated the effect of ACTS on overall survival and its safety.
In2015, we launched ACTS study (NCT02562365), and the primary results showed benefit of ACTS on PFS and acceptable AE. Currently, PARP inhibit was shown to be effective in maintainance therapy in ovarian cancer especially approve for BRCA1/2 mutated pateints. However there is no standard maintainance therapy for BRCA1/2 wide-type ovarian cancer. Here we started ACTS-2 study to verify the effectivity and safety of ACTS in BRCA1/2 wide-type ovarian cancer patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
adjuvent chemotherapy, ovarian cancer, maitainance therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
590 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Follow-up
Arm Type
No Intervention
Arm Description
No interevention
Arm Title
three steps chemotherapy
Arm Type
Experimental
Arm Description
Cyclophosphamide 400mg(250mg/m2)+Etoposide 100mg (70mg/m2)d1-d3 iv 4w/6cycles , followed by Carboplatin (AUC=5)+Cyclophosphamide 600mg(400mg/m2)d1-d2 iv 8w/6cycles.
Intervention Type
Drug
Intervention Name(s)
Etoposide, Cyclophosphamide, Carboplatin/Cisplatin
Intervention Description
CTX 400mg(250mg/m2)+VP-16 100mg (70mg/m2)d1-d3 iv 4w/6cycles , CBP(AUC=5) d1/CDDP 30mg/m2 d1-d2+CTX 600mg(400mg/m2)d1-d2 iv 8w/6cycles
Primary Outcome Measure Information:
Title
Progression-Free-Survival (PFS)
Time Frame
three year
Secondary Outcome Measure Information:
Title
overall survival (OS)
Time Frame
five year
Title
Health-related quality of life questionnaire
Time Frame
three year
Title
Adverse Events (AE)
Time Frame
three year
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
self-representation of gender identity
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patients 18-75 years of age.
ECOG 0-2
Histologically-confirmed epithelial ovarian or fallopian-tube cancer or primary peritoneal cancer
FIGO2018 stage III/IV,
Patients should have received optimal cytoreductive surgery with residual tumor ≤ 1cm and no more than 9 cycle paclitaxel + platinum chemotherapy achieved complete remission (accessed ) and normal CA125.
No more than 8 months after the last chemotherapy.
Adequate bone marrow and hepatic function at Screening:
Hemoglobin ≥9 g/dL
White blood cell count ≥3.0 × 109/L
Absolute neutrophil count ≥1.5 × 109/L
Platelet count ≥100 × 109/L
AST (SGOT)/ALT (SGPT) ≤2.5 ULN
Bilirubin <1.5 × ULN
Creatinine <1.5 × ULN.
Ability and willingness to give written informed consent.
Tumor BRCA1/2 wilde type (qualified center test)
Exclusion Criteria:
Primary or secondary immune deficiency.
Any uncontrolled medical condition that may put the patient at high risk during treatment .
Receipt of any other investigational medicinal product within the last 30 days before randomization.
Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥ 5 years.
Severe heart/ lung/ liver/ kidney failure.
uncontroled or active infection disease.
Legal incompetence, limited legal competence, or detainment in an institution for official or legal reasons.
Receipt of pelvic or abdominal radiotherapy
Mucinous adenocarcinoma, low grade carcinoma
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
zhong zheng, dr
Phone
862164175590
Ext
66073
Email
alizheng@126.com
Facility Information:
Facility Name
Wu Xiaohua
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200023
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
zhong zheng, MD&PHD
Phone
862164175590
Ext
66073
Email
alizheng@126.com
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
data is available per require after approved by ethics broad.
Learn more about this trial
Adjuvant Chemotherapy of Three-step Regimen in BRCA1/2 Wide Type Ovarian Cancer (ACTS-2)
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