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.
Brief Title
A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors
Categories
Completion Date
Completion Date Type
Actual
Conditions
Locally Advanced or Metastatic Solid Tumor
Eligibility Criteria
Inclusion Criteria:
1. Male or female patients ≥18 years of age at the time of informed consent
2. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
3. Part 2
* Triple-negative and Stage IV inflammatory breast cancer
* 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
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2
5. Able to provide an archival tumor tissue sample
6. Adequate organ function and bone marrow reserve
7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment
8. Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures
Exclusion Criteria:
1. Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose
2. Not recovered from prior-treatment toxicities to Grade ≤1
3. Peripheral neuropathy of any etiology \>Grade 1
4. Concurrent malignancy
5. Known active central nervous system (CNS) metastases
6. Use of systemic corticosteroids
7. Known retinal neovascularization, macular edema or macular degeneration
8. History or presence of clinically relevant cardiovascular abnormalities
9. QT interval corrected by Fridericia's formula (QTcF) \>450 ms in males or \>470 ms in females
10. Left ventricular ejection fraction (LVEF) \<50% at screening
11. Arterial thrombotic or embolic events
12. Venous thrombotic event
13. Active infection ≥Grade 3
14. Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (HBV), or active HCV infection
15. Use of proton pump inhibitors
16. If female, the patient is pregnant or lactating
17. Major surgery 4 weeks prior to the first dose of study drug
18. Malabsorption syndrome or other illness which could affect oral absorption
19. Known allergy or hypersensitivity to any component of rebastinib or any of its excipients.
20. Any other clinically significant comorbidities
1. Male or female patients ≥18 years of age at the time of informed consent
2. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
3. Part 2
* Triple-negative and Stage IV inflammatory breast cancer
* 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
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2
5. Able to provide an archival tumor tissue sample
6. Adequate organ function and bone marrow reserve
7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment
8. Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures
Exclusion Criteria:
1. Received prior anticancer or other investigational therapy within 28 days or 5× the half-life prior to the first dose
2. Not recovered from prior-treatment toxicities to Grade ≤1
3. Peripheral neuropathy of any etiology \>Grade 1
4. Concurrent malignancy
5. Known active central nervous system (CNS) metastases
6. Use of systemic corticosteroids
7. Known retinal neovascularization, macular edema or macular degeneration
8. History or presence of clinically relevant cardiovascular abnormalities
9. QT interval corrected by Fridericia's formula (QTcF) \>450 ms in males or \>470 ms in females
10. Left ventricular ejection fraction (LVEF) \<50% at screening
11. Arterial thrombotic or embolic events
12. Venous thrombotic event
13. Active infection ≥Grade 3
14. Human immunodeficiency virus (HIV) or hepatitis C (HCV) infection only if taking medications excluded per protocol, active hepatitis B (HBV), or active HCV infection
15. Use of proton pump inhibitors
16. If female, the patient is pregnant or lactating
17. Major surgery 4 weeks prior to the first dose of study drug
18. Malabsorption syndrome or other illness which could affect oral absorption
19. Known allergy or hypersensitivity to any component of rebastinib or any of its excipients.
20. Any other clinically significant comorbidities
Inclusion Criteria
Inclusion Criteria:
1. Male or female patients ≥18 years of age at the time of informed consent
2. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
3. Part 2
* Triple-negative and Stage IV inflammatory breast cancer
* 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
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2
5. Able to provide an archival tumor tissue sample
6. Adequate organ function and bone marrow reserve
7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment
8. Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures
1. Male or female patients ≥18 years of age at the time of informed consent
2. Part 1 Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel is considered appropriate treatment
3. Part 2
* Triple-negative and Stage IV inflammatory breast cancer
* 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
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2
5. Able to provide an archival tumor tissue sample
6. Adequate organ function and bone marrow reserve
7. If a female of childbearing potential, must have a negative pregnancy test prior to enrollment
8. Patient must provide signed consent to participate in the study and is willing to comply with study-specific procedures
Gender
All
Gender Based
false
Keywords
rebastinib
paclitaxel
breast cancer
ovarian cancer
endometrial cancer
gynecological carcinosarcoma
malignant mixed Mullerian tumor (MMMT)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03601897
Org Class
Industry
Org Full Name
Deciphera Pharmaceuticals, LLC
Org Study Id
DCC-2036-01-003
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
An Open-Label, Multicenter, Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced or Metastatic Solid Tumors
Primary Outcomes
Outcome Description
Number of participants (pts) who experienced serious adverse events (SAE) and adverse events (AE).
Outcome Measure
Number of Participants With Adverse Events
Outcome Time Frame
Baseline up to 2.89 years
Outcome Description
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.
Outcome Measure
Objective Response Rate (ORR) (Part 2 Expansion)
Outcome Time Frame
Baseline to PD or Death due to Any Cause (Up to 1.54 years)
Secondary Outcomes
Outcome Description
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
Outcome Time Frame
Baseline to PD or Death due to Any Cause (Up to 0.92 years)
Outcome Measure
Objective Response Rate (ORR) (Part 1 Escalation)
Outcome Description
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.
Outcome Time Frame
Time from CR or PR to PD or Death due to Any Cause (Up to 1.54 years)
Outcome Measure
Duration of Response (DOR)
Outcome Description
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.
Outcome Time Frame
First Dose of Study Drug to PD (Up to 2.61 years)
Outcome Measure
Time to Progression (TTP)
Outcome Description
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.
Outcome Time Frame
First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years)
Outcome Measure
Progression-free-survival (PFS)
Outcome Description
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.
Outcome Time Frame
First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years)
Outcome Measure
Overall Survival (OS)
Outcome Description
Measure the Cmax
Outcome Time Frame
Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
Outcome Measure
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)
Outcome Description
Measure the AUC 0-6 hours
Outcome Time Frame
Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
Outcome Measure
PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Investigator Phone