Recruiting
Phase 3
A Study of Azenosertib (ZN-c3) Versus Investigator's Choice Chemotherapy in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression
Condition(s) studied
Ovarian Cancer
Investigational drug(s) / intervention(s)
Investigator's choice of Chemotherapy: The investigator will select the chemotherapy in accordance with the protocol defined requirements. The possible choices as defined by the protocol:
* Paclitaxel
* Gemcitabine
* Pegylated liposomal doxorubicin (PLD)
* Topotecan
The selected chemotherapy will be administered intravenously
Azenosertib: Azenosertib 400 mg will be administered orally.
Study summary
This is a randomized, Phase 3 trial designed to evaluate the efficacy and safety of azenosertib compared to Investigator's choice of chemotherapy in subjects with platinum-resistant ovarian cancer whose tumors are positive for cyclin E1 protein expression.
Eligibility
Inclusion Criteria:
1. Female age ≥ 18 years
2. High-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer
3. Measurable disease per RECIST Version 1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
5. The subject's tumor tissue must be positive for cyclin E1 protein expression per the Sponsor's clinically validated cyclin E1 IHC investigational, in vitro diagnostic assay
6. Prior Therapy:
1. Subject must have platinum-resistant disease
2. One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
3. Prior bevacizumab treatment is required, if eligible per standard of care
4. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
5. Prior mirvetuximab treatment is required, if eligible per standard of care
7. Adequate hematologic and organ function during the screening period
Exclusion Criteria:
1. History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease-free. Exceptions include appropriately treated carcinoma in situ of the cervix, nonmelanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome.
2. Subjects with primary platinum-refractory disease.
3. Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or (PKMYT1) inhibitor for PROC.
4. A serious illness or medical condition(s) including, but not limited to, the following:
1. Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
2. Acute kidney injury requiring intervention, or presence of indwelling urinary catheter or percutaneous nephrostomy.
3. Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for IV alimentation, active peptic ulcer, chronic diarrhea or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption.
4. Any evidence of small bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for small bowel obstruction within 3 months before randomization, or recurrent paracentesis or thoracentesis within 6 weeks before randomization.
5. Active, uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral) must have completed such treatment and the infection must be considered controlled/resolved (and afebrile) by the Investigator for at least 7 days before randomization
6. Myocardial impairment of any cause resulting in heart failure by New York Heart Association criteria (Class II, III or IV).
7. Medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results
5. Any of the following treatment interventions within the specified time frame before randomization:
1. Hospitalization within 14 days
2. Major surgery within 28 days
3. Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter)
4. Radiation therapy within 21 days
5. Autologous or allogeneic stem cell transplant within 3 months
6. Current use of any other investigational drug therapy \< 28 days or 5 half-lives (whichever is shorter)
6. Inability to discontinue treatment with prescription or nonprescription drugs that are prohibited per protocol.
7. Inability to discontinue consumption of food and herbal supplements that are prohibited per protocol
8. Prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.
9. Unresolved toxicity of Grade \> 1 attributed to any prior therapies (excluding Grade ≤ 2 neuropathy, alopecia, or skin pigmentation).
10. Subjects who are immunocompromised or HIV-positive on highly active anti-retroviral therapy
11. Subjects with known active hepatitis B or hepatitis C infection
12. Individuals who are judged by the Investigator to be unsuitable as study subjects
Primary outcome measure(s)
- Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator — Up to approximately 24 months from the enrollment of the last subject
Time from randomization to the first documented tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.
Trial sites (59)
| Facility | City | Region | Status |
| Site 0107 |
Phoenix |
Arizona |
Not Yet Recruiting |
| Site 0110 |
Antioch |
California |
Not Yet Recruiting |
| Site 0104 |
Beverly Hills |
California |
Recruiting |
| Site 0115 |
San Francisco |
California |
Not Yet Recruiting |
| Site 0101 |
Torrance |
California |
Recruiting |
| Site 0111 |
Camden |
New Jersey |
Not Yet Recruiting |
| Site 0108 |
Columbus |
Ohio |
Not Yet Recruiting |
| Site 0105 |
Portland |
Oregon |
Not Yet Recruiting |
| Site 0109 |
Philadelphia |
Pennsylvania |
Not Yet Recruiting |
| Site 0113 |
Philadelphia |
Pennsylvania |
Not Yet Recruiting |
| Site 0114 |
Willow Grove |
Pennsylvania |
Not Yet Recruiting |
| Site 0112 |
Sioux Falls |
South Dakota |
Not Yet Recruiting |
| Site 1101 |
Randwick |
New South Wales |
Not Yet Recruiting |
| Site 1102 |
Adelaide |
South Australia |
Recruiting |
| Site 1103 |
Nedlands |
Australia |
Not Yet Recruiting |
| Site 3002 |
Brussels |
Belgium |
Not Yet Recruiting |
| Site 3001 |
Leuven |
Belgium |
Not Yet Recruiting |
| Site 0201 |
Toronto |
Ontario |
Not Yet Recruiting |
| Site 0204 |
Montreal |
Quebec |
Not Yet Recruiting |
| Site 0203 |
Montreal |
Quebec |
Not Yet Recruiting |
| Site 0202 |
Sherbrooke |
Quebec |
Not Yet Recruiting |
| Site 3508 |
Besançon |
France |
Not Yet Recruiting |
| Site 3502 |
Brest |
France |
Not Yet Recruiting |
| Site 3507 |
Dijon |
France |
Not Yet Recruiting |
| Site 3504 |
Lyon |
France |
Not Yet Recruiting |
| Site 3503 |
Paris |
France |
Not Yet Recruiting |
| Site 3501 |
Pierre-Bénite |
France |
Not Yet Recruiting |
| Site 3509 |
Saint-Herblain |
France |
Not Yet Recruiting |
| Site 3505 |
Strasbourg |
France |
Not Yet Recruiting |
| Site 3506 |
Villejuif |
France |
Not Yet Recruiting |
| Site 3602 |
Berlin |
Germany |
Not Yet Recruiting |
| Site 3601 |
Dresden |
Germany |
Not Yet Recruiting |
| Site 3703 |
Cork |
Ireland |
Not Yet Recruiting |
| Site 3702 |
Dublin |
Ireland |
Not Yet Recruiting |
| Site 3801 |
Bologna |
Italy |
Not Yet Recruiting |
| Site 3805 |
Milan |
Italy |
Not Yet Recruiting |
| Site 3804 |
Milan |
Italy |
Not Yet Recruiting |
| Site 3803 |
Milan |
Italy |
Not Yet Recruiting |
| Site 3802 |
Naples |
Italy |
Not Yet Recruiting |
| Site 3807 |
Prato |
Italy |
Not Yet Recruiting |
+ 19 more sites — see the full list on the official registry below.
More K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc trials in Italy
Other trials for the same condition