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.

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.

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

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data is available per require after approved by ethics broad.