Clinical trial NCT03895788: A Study of Niraparib in Combination With Brivanib in Recurrent Ovarian Cancer
Official title: An Open-Label, Single-Arm, Phase I Clinical Trial to Evaluate the Safety and Tolerability of ZL-2306 (Niraparib) in Combination With Brivanib in Patients With Recurrent Ovarian Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Ovarian Cancer
Lead sponsor: Hunan Cancer Hospital
Sponsor class: OTHER
First posted: 2019-03-29
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Open-label, cohort study to determine the safety and tolerability of the combination of daily niraparib and daily brivanib for one 28-day cycle in patients with advanced ovarian cancer.


Eligibility criteria: Inclusion Criteria:

1. Signed informed consent .
2. Female, age ≥ 18 years.
3. Histologically confirmed diagnosis of ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
4. Patients must have ovarian cancer and have failed at least 1 prior line of therapy
5. Life expectancy of more than 16 weeks.
6. ECOG 0-1.
7. Patient agrees to blood draws during study for the gBRCA test
8. Has good organ function, including:

   * Absolute neutrophil count ≥1,500/µL
   * Platelets ≥125,000/µL
   * Hemoglobin ≥10 g/dL
   * Serum creatinine ≤1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥60 mL/min using the Cockcroft-Gault equation
   * Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤1 x ULN
   * Aspartate aminotransferase and alanine aminotransferase ≤2.5 x ULN unless liver metastases are present, in which case they must be ≤5 x ULN
9. Female patient has a negative serum pregnancy test within 3 days prior to taking study treatment if of childbearing potential and agrees to abstain from activities that could result in pregnancy from screening through 3 months after the last dose of study treatment, or is of non-childbearing potential. Non-childbearing potential is defined as follows (by other than medical reasons):

   * ≥45 years and \<60 years of age and has not had menses for \>1 year
   * ≥60 years of age
   * Post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation.
10. Is able to adhere to the protocol.
11. Has recovered from previous chemotherapy induced toxic side effects to ≤ grade 1 CTCAE or basal level, apart from ≤ grade 2 CTCAE peripheral neuropathy or hair loss symptoms at steady state.

Exclusion Criteria:

1. Has a known hypersensitivity to the active or inactive ingredients of ZL-2306 (niraparib) or compound which has similar chemical structure to ZL-2306 (niraparib).
2. Has a known hypersensitivity to the active or inactive ingredients of brivanib or compound which has similar chemical structure to brivanib.
3. Has symptomatic uncontrolled brain or leptomeningeal metastasis.
4. Major surgery or chemotherapy within 3 weeks of starting the study or patient has not recovered from any effects of the surgery.
5. Receive palliative radiotherapy encompassing \> 20% of the bone marrow within 1 week of entering the study.
6. Be diagnosed any invasive cancer other than ovarian cancer (apart from cured basal cell carcinoma and squamous cell carcinoma) within 2 years prior to study enrolment.
7. Patient must has any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
8. Has other serious or uncontrolled disease
9. Has any disease, treatment and laboratory abnormality that may interfere the study results and affect the fully attendance of study. Or the patient is considered to be not suitable for the study by the investigator. Cannot receive platelet or red blood cell transfusion within 4 weeks of study drug administration.
10. Pregnant, breastfeeding or expecting to conceive children during the study treatment period.
11. Corrected QT (QTc) interval \> 450 msec.
12. Prior PARP inhibitor therapy

Primary outcomes:
measure: Maximum tolerated dose
timeFrame: 1 year
Secondary outcomes:
measure: Assess the toxicity of the combination of niraparib and brivanib in each cohort by number of participants with treatment related adverse events
timeFrame: 1 year
Other outcomes:
Locations:
city: Changsha
country: China
facility: Jing Wang
state: Hunan
Study officials:
References: