A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors
- Conditions
- Locally Advanced or Metastatic Solid Tumor
- Interventions
- Registration Number
- NCT03601897
- Lead Sponsor
- Deciphera Pharmaceuticals, LLC
- Brief Summary
This is an open-label Phase 1b/2 multicenter study of rebastinib (DCC-2036) in combination with paclitaxel designed to evaluate the safety, tolerability, and pharmacokinetics (PK) in patients with advanced or metastatic solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 177
-
Male or female patients ≥18 years of age at the time of informed consent
-
Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
-
Part 2
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Triple-negative and Stage IV inflammatory breast cancer
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Recurrent ovarian cancer
-
Recurrent, metastatic or high-risk endometrial cancer
-
Advanced (stage III or IV), or recurrent gynecological carcinosarcoma
- Homologous or heterologous type carcinosarcoma (malignant mixed Mullerian tumor [MMMT] allowed
-
-
Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2
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Able to provide an archival tumor tissue sample
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Adequate organ function and bone marrow reserve
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If a female of childbearing potential, must have a negative pregnancy test prior to enrollment
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Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures
- Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose
- Not recovered from prior-treatment toxicities to Grade ≤1
- Peripheral neuropathy of any etiology >Grade 1
- Concurrent malignancy
- Known active central nervous system (CNS) metastases
- Use of systemic corticosteroids
- Known retinal neovascularization, macular edema or macular degeneration
- History or presence of clinically relevant cardiovascular abnormalities
- QT interval corrected by Fridericia's formula (QTcF) >450 ms in males or >470 ms in females
- Left ventricular ejection fraction (LVEF) <50% at screening
- Arterial thrombotic or embolic events
- Venous thrombotic event
- Active infection ≥Grade 3
- Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (HBV), or active HCV infection
- Use of proton pump inhibitors
- If female, the patient is pregnant or lactating
- Major surgery 4 weeks prior to the first dose of study drug
- Malabsorption syndrome or other illness which could affect oral absorption
- Known allergy or hypersensitivity to any component of rebastinib or any of its excipients.
- Any other clinically significant comorbidities
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in inflammatory breast cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in endometrial cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose escalation of rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in combination with paclitaxel administered by intravenous (IV) infusion at 80 mg/meter squared (m\^2) on days 1, 8, and 15 of repeated 28-day cycles. Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose escalation of rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in triple-negative breast cancer (TNBC). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in TNBC. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in inflammatory breast cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in ovarian cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 repeated 28-day cycles. Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in ovarian cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in endometrial cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Rebastinib Dose expansion in gynecological carcinosarcoma (GCS). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose escalation of rebastinib 50 milligram (mg) twice daily (BID) orally (PO) in combination with paclitaxel administered by intravenous (IV) infusion at 80 mg/meter squared (m\^2) on days 1, 8, and 15 of repeated 28-day cycles. Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose escalation of rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in triple-negative breast cancer (TNBC). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in TNBC. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in inflammatory breast cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in inflammatory breast cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in ovarian cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 repeated 28-day cycles. Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in ovarian cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in endometrial cancer. Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in endometrial cancer. Rebastinib 100 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles. Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2 Paclitaxel Dose expansion in gynecological carcinosarcoma (GCS). Rebastinib 50 mg BID PO in combination with paclitaxel IV infusion at 80 mg/m\^2 on days 1, 8, and 15 of repeated 28-day cycles.
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events Baseline up to 2.89 years Number of participants (pts) who experienced serious adverse events (SAE) and adverse events (AE).
Objective Response Rate (ORR) (Part 2 Expansion) Baseline to PD or Death due to Any Cause (Up to 1.54 years) Percentage of participants who achieved an objective response of Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumor (RECIST) v1.1. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to \<10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR) (Part 1 Escalation) Baseline to PD or Death due to Any Cause (Up to 0.92 years) Percentage of pts who achieved an objective response of Complete Response (CR) or Partial Response (PR). Per RECIST v1.1, CR defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. Modified RECIST (mRECIST) used for pleural mesothelioma defines CR as the disappearance of any intratumoural arterial enhancement in all target lesions; PR as at least a 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions; PD as an increase of at least 20% in the sum of the diameters of viable target les
Duration of Response (DOR) Time from CR or PR to PD or Death due to Any Cause (Up to 1.54 years) Time from CR or PR to the earliest documented evidence of PD or death due to any cause. Per RECIST v1.1, CR defined as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have reduction in short axis to \<10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study, or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines CR as the disappearance of any intratumoural arterial enhancement in all target lesions; PR as at least a 30% decrease in the sum of diameters of viable target lesions, taking as reference the baseline sum of the diameters of target lesions; PD as an increase of at least 20% in the sum of the diameters of viable target lesions.
Time to Progression (TTP) First Dose of Study Drug to PD (Up to 2.61 years) Time from first dose of study drug to the earliest documented evidence of PD. Per RECIST v1.1, PD defined as at least a 20% increase in the sum of the disease measurements for measurable lesions, taking as reference the smallest disease measurement recorded since the start of treatment, or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines PD as an increase of at least 20% in the sum of the diameters of viable target lesions.
Progression-free-survival (PFS) First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years) Time from first dose of study drug to the earliest documented evidence of PD or death due to any cause. Participants who undergo surgical resection of target or non-target lesions, who have received other anticancer treatments, including surgical resection or radiation (other than palliative radiation to pre-existing bone metastases'), or who do not have a documented date of progression or death due to any cause will be censored at the date of the last assessment. PD per RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline; or the appearance of one or more new lesions. mRECIST used for pleural mesothelioma defines PD as an increase of at least 20% in the sum of the diameters of viable target lesions.
Overall Survival (OS) First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years) Time from first dose of study drug to date of death due to any cause. Participants who were still alive or who were lost to follow-up will be censored at the date of last contact.
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1) Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days) Measure the Cmax
PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1) Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days) Measure the AUC 0-6 hours
Trial Locations
- Locations (14)
The University of Kansas Clinical Research Center
🇺🇸Kansas City, Kansas, United States
Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Alabama Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
University of Colorado Denver- Anschutz Medical Center
🇺🇸Aurora, Colorado, United States
Northwestern University Feinberg School of Medicine
🇺🇸Chicago, Illinois, United States
Dana-Farber
🇺🇸Boston, Massachusetts, United States
Northwell Health/Monter Cancer Center
🇺🇸Lake Success, New York, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Oklahoma Health Sciences Center
🇺🇸Oklahoma City, Oklahoma, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States
Women & Infants Hospital
🇺🇸Providence, Rhode Island, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Oncology Consultants- Texas Medical Center
🇺🇸Houston, Texas, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States