A Multicenter, Randomized, Double-Blind, Phase II Clinical Study of IN10018 in Combination With Pegylated Liposomal Doxorubicin (PLD) vs. Placebo in Combination With PLD for the Treatment of Platinum-resistant Recurrent Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pegylated Liposomal Doxorubicin
- Conditions
- Ovarian Cancer Recurrent
- Sponsor
- InxMed (Shanghai) Co., Ltd.
- Enrollment
- 168
- Locations
- 1
- Primary Endpoint
- Progression-free survival (PFS) per RECIST 1.1, as assessed by blinded independent central review (BICR), following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a multicenter, randomized, double-blind, phase II clinical study to evaluate the efficacy and safety of IN10018 in combination with PLD vs. placebo in combination with PLD in subjects with platinum-resistant recurrent ovarian cancer (including fallopian tube and primary peritoneal cancers).
Detailed Description
This is a multicenter, randomized, double-blind, Phase II clinical study to evaluate the efficacy and safety of IN10018 in combination with PLD vs. placebo in combination with PLD in subjects with platinum-resistant recurrent ovarian cancer (including fallopian tube and primary peritoneal cancers). Approximately 168 subjects will be enrolled into the study. Eligible subjects will be randomized in a 2: 1 ratio to receive IN10018 in combination with PLD treatment (Experimental Arm, N = approx. 112) or placebo of IN10018 in combination with PLD (Control Arm, N = approx. 56). Subjects will be stratified by prior bevacizumab use (yes or no) and platinum free interval (PFI, \< 3 months or 3-6 months). Subjects will be randomized to one of following treatment arms. The investigator should follow the clinical study protocol, the approved label of these drugs and/or institutional standard of care. * Experimental Arm: IN10018 100 mg QD orally (PO) plus PLD 40 mg/m2 once every 4 weeks (Q4W) intravenously (IV). * Control Arm: Placebo of IN10018 100 mg QD orally (PO) plus PLD 40 mg/m2 once every 4 weeks (Q4W) intravenously (IV).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Ability to understand and willingness to sign informed consent(s). Signed informed consent must be obtained before any study specific procedures, except those procedures used as institutional standard of care falling into the protocol specified window and fulfilling study specific requirements such as tumor imaging.
- •Female subjects ≥ 18 years at the time of signing informed consent.
- •Histologically confirmed epithelial ovarian cancer, fallopian tube cancer or primary peritoneum cancer and its subtype is high-grade serous carcinoma (HGSC).
- •Have received platinum containing therapy and have radiological relapse or progression during platinum containing treatment or \< 6 months (184 calendar days) after completion of prior platinum-based therapy (at least 4 cycles).
- •Note: Disease progression or recurrence requires evidence of radiographic or clinical progression (e.g., new ascites or cytological reports of pleural fluid), and elevated CA125 alone is not a criterion for progression or recurrence. Primary platinum-refractory ovarian cancers (defined as progression during or within 4 weeks after first line platinum-based therapy) is excluded, while secondary platinum-refractory disease is allowed and does not require at least 4 cycles of platinum-based therapy.
- •Maximum total of 3 prior lines of systemic therapy are allowed. Note: Hormonal therapies (e.g., tamoxifen), PARP inhibitors and bevacizumab given in the maintenance setting post response to platinum-based therapy will not count as a treatment line. Other maintenance regimens may also not count as a treatment line by discussion between the investigator and sponsor.
- •At least one measurable lesion can be accurately measured per RECIST 1.1 as assessed by investigator.
- •Note: Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
- •ECOG performance status of 0 or
- •Life expectancy of at least 3 months as assessed by investigator.
Exclusion Criteria
- •Has had major surgery or significant traumatic injury within 28 days prior to randomization, or diagnostic biopsies within 14 days prior to randomization.
- •Note: Subjects with anticipation of the need for major surgery during study treatment should be excluded. Subjects who underwent diagnostic biopsy within 14 days prior to randomization may also be enrolled if the investigator and sponsor determine that the diagnostic biopsy will not affect the efficacy evaluation.
- •Has received prior systemic anticancer therapy including investigational agents, such as within 14 days or less than 5 half-lives (whichever is shorter) of chemotherapy or targeted therapy, or within 28 days of immunotherapy, macromolecular drugs (eg., bevacizumab) or investigational drugs prior to randomization.
- •Has received prior radiotherapy within 14 days prior to randomization. Note: A 7-day washout is permitted for palliative radiation (≤ 14 days of radiotherapy) to non-central nervous system (CNS) disease.
- •Has received prior treatment of any FAK inhibitor or prior treatment of PLD.
- •Has a known previous or concurrent cancer that is distinct in primary site or histology from current ovarian cancer within 3 years prior to randomization, except for curatively treated cancers such as cervical/breast/prostate carcinoma in situ and basal cell carcinoma.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Note: Subjects with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression) for at least 4 weeks apart by repeat imaging (note that the repeat imaging should be performed during screening phase) for at least 28 days prior to randomization.
- •Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases (e.g., congestive heart failure, acute myocardial infarction, unstable angina, stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism) within 6 months before randomization, or has any of the following abnormality:
- •QTc interval corrected using Fridericia's formula \> 470 ms (based on QTcF).
Arms & Interventions
Experimental Arm
IN10018+PLD
Intervention: Pegylated Liposomal Doxorubicin
Experimental Arm
IN10018+PLD
Intervention: IN10018
Control Arm
Placebo of IN10018+PLD
Intervention: Placebo of IN10018
Control Arm
Placebo of IN10018+PLD
Intervention: Pegylated Liposomal Doxorubicin
Outcomes
Primary Outcomes
Progression-free survival (PFS) per RECIST 1.1, as assessed by blinded independent central review (BICR), following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.
Time Frame: 2 years.
PFS per RECIST 1.1, as assessed by BICR.
Secondary Outcomes
- Disease control rate (DCR) per RECIST 1.1, as assessed by BICR and Investigator, following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.(2 years.)
- Duration of response (DoR) per RECIST 1.1, as assessed by BICR and Investigator, following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.(2 years.)
- Safety and tolerability of IN10018 in combination with PLD vs. placebo in combination with PLD.(2 years.)
- Overall survival (OS), following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.(3 years.)
- Progression-free survival (PFS) per RECIST 1.1, as assessed by investigator , following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.(2 years.)
- Objective response rate (ORR) per RECIST 1.1, as assessed by BICR and Investigator, following treatment of IN10018 in combination with PLD vs. placebo in combination with PLD.(2 years.)