Fluzoparib Combined With Bevacizumab in PSROC Previously Treated With PARPi

Ovarian Cancer Clinical Trial

Official title:

A Prospective, Single-arm, Multicenter Phase Ⅱ Clinical Study of Fluzoparib Combined With Bevacizumab in Platinum-sensitive Recurrent Ovarian Cancer Patients Previously Treated With PARPi

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05551208
• Other study ID #: CQGOG0205
• Status: Recruiting
• Phase: Phase 2
• Start date: August 15, 2022
• Est. completion date: August 30, 2029

Study information

• Verified date: September 2022
• Source: Chongqing University Cancer Hospital
• Contact: Zou Dongling, PH.D.
• Phone: +8613657690699
• Email: cqzl_zdl[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

There are more and more PARPi(PARP inhibitors) resistance for ovarian cancer patients after previous use of PARP inhibitors. Basic studies have found that there is synergistic effect of bevacizumab combined with PARPi. Therefore we designed the study to include 42 ovarian cancer patients who had PARPi for at least half a year and then relapsed (platinum-sensitive, previously 1-3 lines of chemotherapy). After getting complete remission or partial remission with chemotherapy containing platinum and bevacizumab, fluzopanib and bevacizumab were used for maintenance treatment. The progression-free survival, ORR, DCR, DoR, and safety were evaluated based on RECIST V1.1.

Description:

Genetic testing of tissue samples before and after the maintenance therapy were also used to further explore the pattern of gene mutations and the subgroups who may benefit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: August 30, 2029
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Ovarian cancer patients with histopathological type: low/high grade serous carcinoma, endometrioid carcinoma,had received platinum-based regimens for at least 1-3 lines after primary cytoreductive surgery.

2. The patient had at least one measurable lesion according to the RECIST V1.1 criteria.

3. The time from the last cycle of chemotherapy to relapse/progression should be more than 6 months.

4. ECOG score 0~1,age 18~75 years old

5. The serum or urine pregnancy test must be negative within 7 days before enrollment for the women of childbearing age who should agree that contraception must be used during the trial

6. CBC Hb=90g/L, ANC=1.5×109/L, PLT=100×109/L,

7. Serum ALT=3×UL, AST=3×ULN#Serum creatinine=1.5×ULN#

Exclusion Criteria:

1. Had used bevacizumab within 6 months of enrollment

2. Has combined with other malignant tumor which diagnosed within 5 years and/or needed to be treated. The patients had untreated CNS metastases.

3. The patient had Recent intestinal obstruction, gastrointestinal perforation within 3 months, uncontrolled high blood pressure after medication (Systolic blood pressure =140mmHg or diastolic blood pressure =90mmHg), Moderate to severe cerebrovascular accident (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), moderate to severe deep vein thrombosis and moderate to severe pulmonary embolism occurred within 6 months before enrollment. Patient with coagulation dysfunction.

4. Myocardial infarction, severe arrhythmia and NYHA (New York heart association)=2 for congestive heart failure

5. Activity or uncontrol severe infection

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• fluzopanib and bevacizumab
fluzopanib and bevacizumab were used for maintenance treatment

Locations

Country	Name	City	State
China	Chongqing Cancer Hospital	Chongqing	Chongqing

Sponsors (1)

Lead Sponsor	Collaborator
Chongqing University Cancer Hospital

Country where clinical trial is conducted

China, 

References & Publications (8)

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Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, Ashworth A, Carmichael J, Kaye SB, Schellens JH, de Bono JS. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med. 2009 Jul 9;361(2):123-34. doi: 10.1056/NEJMoa0900212. Epub 2009 Jun 24. — View Citation

Harter P, Sehouli J, Vergote I, Ferron G, Reuss A, Meier W, Greggi S, Mosgaard BJ, Selle F, Guyon F, Pomel C, Lécuru F, Zang R, Avall-Lundqvist E, Kim JW, Ponce J, Raspagliesi F, Kristensen G, Classe JM, Hillemanns P, Jensen P, Hasenburg A, Ghaem-Maghami S, Mirza MR, Lund B, Reinthaller A, Santaballa A, Olaitan A, Hilpert F, du Bois A; DESKTOP III Investigators. Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer. N Engl J Med. 2021 Dec 2;385(23):2123-2131. doi: 10.1056/NEJMoa2103294. Erratum in: N Engl J Med. 2022 Feb 17;386(7):704. — View Citation

Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, Fujiwara K, Vergote I, Colombo N, Mäenpää J, Selle F, Sehouli J, Lorusso D, Guerra Alía EM, Reinthaller A, Nagao S, Lefeuvre-Plesse C, Canzler U, Scambia G, Lortholary A, Marmé F, Combe P, de Gregorio N, Rodrigues M, Buderath P, Dubot C, Burges A, You B, Pujade-Lauraine E, Harter P; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med. 2019 Dec 19;381(25):2416-2428. doi: 10.1056/NEJMoa1911361. — View Citation

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Outcome

Type	Measure	Description	Time frame	Safety issue
Other	saftey	The severity of adverse events was determined according to CTCAE V5.0 criteria. During the trial, the adverse event record form should be truthfully filled in, including the occurrence time, severity, correlation with study treatment, duration, measures taken and outcome of the adverse event	5 years
Primary	PFS	progression-free survival was the maintenance time to progression or recurrence since the last platinum therapy based on RECIST v1.1	5 years
Secondary	OS	Overall survival	5 years
Secondary	ORR	Objective Response Rate	5 years
Secondary	DCR	Disease control rate	5 years
Secondary	DoR	Duration of remission	5 years