Study of TTI-622 in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer
Study Details
Study Description
Brief Summary
This is a multi-center, open-label study designed to evaluate TTI-622 administered in combination with Pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer. Approximately 50 patients will be enrolled in the study (this includes two phases, the Dose Escalation and Dose Expansion).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
Pegylated liposomal doxorubicin (PLD) is a standard treatment option for patients with platinum-resistant ovarian cancer who are not candidates for chemotherapy in combination with bevacizumab. However, despite being consider a standard treatment option, the clinical benefit of chemotherapy for this patient population is small. The goal of this clinical trial is to improve upon the activity of PLD in a safe manner to provide a more effective therapeutic option for this group of patients.
TTI-622-02 is a multi-center, open-label study designed to evaluate TTI-622 administered in combination with PLD in patients with platinum-resistant ovarian cancer and for whom PLD is a reasonable treatment option. The first portion of the study will evaluate the safety of increasing dose levels of TTI-622 in combination with PLD at 40 mg/m2 in patients with platinum-resistant EOC, including ovarian, peritoneal and fallopian tube malignancy, and establish a combination regimen for further evaluation in a dose expansion cohort. The study will consist of a 28-day screening period, a treatment period in which patients will receive TTI-622 in combination with PLD in 28-day cycles until documentation of objective disease progression or development of unacceptable toxicity, and a long-term follow-up period to assess overall survival.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation TTI-622 will be administered with initial dose of 12 mg/kg by intravenous infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 in subsequent cycles. Pegylated Liposomal Doxorubicin (PLD) 40 mg/m^2 by intravenous infusion on Day 1 of each 28-day cycle. |
Drug: TTI-622
TTI-622 will be administered by intravenous infusion.
Drug: Pegylated Liposomal Doxorubicin
Pegylated Liposomal Doxorubicin will be administered by intravenous infusion.
Other Names:
|
| Experimental: Dose Expansion TTI-622 will be administered with selected dose from the escalation phase by intravenous infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 in subsequent cycles. Pegylated Liposomal Doxorubicin 40 mg/m^2 by intravenous infusion on Day 1 of each 28-day cycle |
Drug: TTI-622
TTI-622 will be administered by intravenous infusion.
Drug: Pegylated Liposomal Doxorubicin
Pegylated Liposomal Doxorubicin will be administered by intravenous infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 Pegylated Liposomal Doxorubicin (PLD) in 28-day cycles in escalation phase; type of adverse events [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the type of adverse events.
- Identify the Recommended Phase 2 Dose from the Escalation Phase [First dose date up to 1 year]
Determine Phase 2 Dose for Expansion Phase
- Assess clinical activity of TTI-622 maximum tolerated dose (MTD) or Recommended Phase 2 dose (RP2D) in combination with PLD in the Expansion Phase overall response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) . [First dose date up to 3 years]
Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the overall response rate as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
- Percentage of patients experiencing adverse events [First dose date up to 3 years]
Percentage of patients who reported adverse events while on study
- Percentage of patients with objective response [Up to 3 years]
Evaluation the percentage of patients with objective response (complete response [CR] + partial response [PR]) as defined by RECIST v 1.1 criteria.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; frequency of adverse events. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the frequency of adverse events.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; severity of adverse events. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the severity of adverse events
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; timing of adverse events. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the timing of adverse events.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; causal relationship of adverse events. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the causal relationship of adverse events.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; number of events with changes from baseline in vitals signs. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the number of events with changes from baseline in vital signs.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; number of events with changes from baseline in laboratory assessments. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by number of events with changes from baseline in laboratory assessments.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; by treatment delays. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by treatment delays .
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; by discontinuations. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by discontinuations.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; number of events with changes from baseline in Electrocardiogram (ECG) findings. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by the number of events with changes from baseline in Electrocardiogram (ECG) findings.
- Assess clinical activity of TTI-622 MTD or RP2D in combination with PLD in the Expansion Phase; the other markers of clinical benefit . [First dose date up to 3 years]
Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the other markers of clinical benefit as defined by irRECIST criteria.
- Assess clinical activity of TTI-622 MTD or RP2D in combination with PLD in the Expansion Phase; the disease control rate. [First dose date up to 3 years]
Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the disease control rate[complete response + partial response + stable disease]) (DCR [CR + PR + SD]) as defined by RECIST v1.1 criteria.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; treatment emergent adverse events. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by treatment emergent adverse events.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; serious adverse events. [First dose date up to 3 years]
Characterize the overall safety profile as assessed by serious adverse events.
- Evaluate safety profile of TTI-622 when administered in combination with 40 mg/m2 PLD in 28-day cycles in escalation phase; established MTD [First dose date up to 3 years]
Characterize the overall safety profile as assessed by established MTD.
- Assess clinical activity of TTI-622 MTD or RP2D in combination with PLD in the Expansion Phase; the immune-related Response Evaluation Criteria in Solid Tumors. [First dose date up to 3 years]
Characterize the clinical activity of TTI-622 in combination with PLD based on the assessment of the immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) criteria.
Secondary Outcome Measures
- Duration of progression-free survival (PFS) [Up to 3 years]
Characterize progression-free survival (PFS) as defined by RECIST v1.1 criteria
- Overall Survival (OS) [Up to 3 years]
The length of overall survival will be measured from the date of study treatment initiation until the date of death from any cause.
- Duration of response [Up to 3 years]
Characterize duration of response (DOR) as defined by RECIST v1.1 criteria.
- Time to progression and new metastases [First dose date up to 3 years]
The length of time to progression or new metastases
- Time to worsening of Eastern Cooperative Oncology Group (ECOG) performance status [First dose date up to 3 years]
The length of time to worsening of performance status
Eligibility Criteria
Criteria
Key Inclusion Criteria:
-
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
-
Histologically-confirmed epithelial ovarian cancer (EOC), fallopian tube carcinoma (FTC) or primary peritoneal carcinomas (PPC).
-
Platinum-resistant disease (progression ≥1 month and ≤6 months after a minimum of four cycles of last platinum-based treatment)
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Progression with standard of care therapies, including platinum-based therapies, poly ADP ribose polymerase (PARP) inhibitors or bevacizumab in the platinum-sensitive setting or intolerability to such therapies or patient refusal
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Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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Adequate organ and hematologic function
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No more than four prior treatment regimens for platinum-resistant disease
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All adverse events from prior treatment must be the Common Terminology Criteria for Adverse Events (NCI CTCAE) v5 Grade ≤ 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline.
Key Exclusion Criteria:
-
Platinum-refractory disease (defined as progression on or within 3 months of completing primary first-line platinum-based treatment)
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Non-epithelial histology, including malignant mixed Mullerian tumors
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Ovarian tumors with low malignant potential (i.e., borderline tumors), low grade serous ovarian cancer or carcinosarcoma
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History of acute coronary syndromes.
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History of or current Class II, III, or IV heart failure.
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History or evidence of known central nervous system (CNS) metastases or carcinomatous meningitis.
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Significant bleeding disorders, vasculitis or a significant bleeding episode from the Gastrointestinal (GI) tract.
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History of severe hypersensitivity reactions to antibodies.
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Systemic steroid therapy.
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History or autoimmune disease that has required systemic treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs.
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Prior organ transplantation including allogenic or autologous stem cell transplantation
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Prior treatment with anti-cluster of differentiation 47 (CD47) or anti-SIRPα therapy.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sarcoma Oncology Research Center, Cancer Center of Southern California | Santa Monica | California | United States | 90403 |
| 2 | Sarcoma Oncology Research Center | Santa Monica | California | United States | 90403 |
| 3 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15219 |
| 4 | oncology Consultants, P.A. | Houston | Texas | United States | 77024 |
| 5 | Oncology Consultants, P.A. | Houston | Texas | United States | 77024 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- TTI-622-02
- C4971002