A Study of Azenosertib (ZN-c3) in Patients With Ovarian Cancer

Официальное название

A Phase 1b Study of ZN-c3 in Combination With Chemotherapy or Bevacizumab in Subjects With Ovarian, Peritoneal, or Fallopian Tube Cancer

Обзор

This is a Phase 1b open-label, multicenter study, evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of azenosertib (ZN-c3) in combination with other drugs.

Подробное описание

This is a Phase 1b open-label, multicenter study evaluating the safety, tolerability, preliminary clinical activity, pharmacokinetics (PK), and pharmacodynamics of azenosertib (also known as ZN-c3) in combination with chemotherapy or bevacizumab. This study consists of 2 parts:

Part 1 (completed and no longer recruiting): Azenosertib in combination with chemotherapy Azenosertib was assessed in combination with chemotherapy in subjects with platinum-resistant advanced ovarian, peritoneal, or fallopian tube cancer.

Part 2: Azenosertib in combination with bevacizumab

* Dose Escalation (completed and no longer recruiting): Azenosertib was assessed in combination with bevacizumab as first-line (1L) or second-line (2L) maintenance therapy in subjects with advanced ovarian, peritoneal, or fallopian tube cancer after platinum-based chemotherapy to determine a recommended dose for expansion. * Dose Expansion: Azenosertib will be assessed in combination with bevacizumab as 2L maintenance therapy in subjects with advanced ovarian, peritoneal, or fallopian tube cancer after platinum-based chemotherapy.

Вмешательства

• Препарат Azenosertib
  Investigational drug
• Препарат Carboplatin
  Carboplatin is an approved drug
• Препарат Pegylated liposomal doxorubicin
  Pegylated liposomal doxorubicin (PLD) is an approved drug
• Препарат Paclitaxel
  Paclitaxel is an approved drug
• Препарат Gemcitabine
  Gemcitabine is an approved drug
• Биопрепарат Bevacizumab
  Bevacizumab is an approved drug

Первичные конечные точки

• Part 1: To investigate the safety and tolerability of azenosertib in combination with PLD, carboplatin, paclitaxel, or gemcitabine [Срок оценки: Through study completion, an average of 1 year]
• Part 1: To identify the maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D) of azenosertib in combination with PLD, carboplatin, paclitaxel, or gemcitabine [Срок оценки: Through Cycle 1 (cycle is 28 days for PLD or paclitaxel, and 21 days for carboplatin, or gemcitabine)]
• Part 2: To estimate the safety/tolerability of azenosertib in combination with bevacizumab [Срок оценки: Through study completion, an average of 1 year]
• Part 2: To identify the recommended dose for Part 2 Dose Expansion [Срок оценки: Through Cycle 1 (21 days)]

Критерии участия

Критерии включения

For Part 1:

• Histologically or cytologically confirmed FIGO Stage III/IV high-grade serous or endometrioid ovarian, fallopian tube, or peritoneal carcinoma.
• Subjects must have received 1 or 2 prior therapeutic regimens/lines of therapy in the advanced or metastatic setting. At least one regimen must have contained cisplatin or carboplatin.
• The disease must be platinum resistant (ie, the PFI must have been < 6 months). Platinum refractory disease (ie, PD during first-line platinum-based therapy) is allowed.

For Part 2 Dose Escalation:

Prior therapy:

• Subjects must have received 6 cycles of platinum-based doublet chemotherapy in the 1L or 2L setting as their most recent therapy

Response to prior platinum therapy:

• In the 1L setting: Complete Response, Partial Response, or Stable Disease to platinum-based chemotherapy.
• In the 2L setting:

• Progressive Disease >183 days after receiving the last dose of platinum chemotherapy in the 1L setting,
• Complete Response, Partial Response, or Stable Disease to 2L platinum-based chemotherapy.

• Adequate hematologic, and organ function

For Part 2 Dose Expansion:

• Subjects must have at least 4 cycles of platinum-based chemotherapy in 2L and have Complete Response, Partial Response, or Stable Disease
• Subjects must have progressed while on a PARP inhibitor for 1L maintenance Additional protocol-defined inclusion criteria may apply

Критерии исключения

• Histology of abdominal adenocarcinoma of unknown origin or diagnosis of a borderline ovarian tumor.
• Subjects with carcinosarcomas (even if there is a serous component)
• A serious illness or medical condition(s)
• Subjects with active (uncontrolled, metastatic) second malignancies or requiring therapy.

Additional protocol-defined exclusion criteria may apply

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 8 центров

• Site 0264 — Aurora
• Site 0104 — Boston
• Site 0111 — St Louis
• Site 0173 — New York
• Site 0259 — Durham
• Site 0191 — Providence
• Site 0196 — Nashville
• Site 0103 — Houston

Австралия · 6 центров

• Site 2707 — South Brisbane
• Site 2708 — Sunshine Coast
• Site 2709 — Adelaide
• Site 2716 — Melbourne
• Site 2706 — Melbourne
• Site 2705 — Nedlands

Bosnia and Herzegovina · 3 центра

• Site 1001 — Banja Luka
• Site 1002 — Sarajevo
• Site 1003 — Tuzla

South Korea · 3 центра

• Site 2901 — Busan
• Site 2903 — Seoul
• Site 2904 — Seoul

Болгария · 2 центра

• Site 1202 — Panagyurishte
• Site 1201 — Sofia

Грузия · 1 центр

• Site 1401 — Tbilisi

Сербия · 1 центр

• Site 1902 — Belgrade

Идентификаторы

NCT: NCT04516447 · ZN-c3-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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