A Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Paclitaxel in Patients With Advanced or Metastatic Solid Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Locally Advanced or Metastatic Solid Tumor
• Intervention / Treatment: Drug: Rebastinib; Drug: Paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University Of Alabama Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver- Anschutz Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Clinical Research Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • Lake Success, New York, United States, 11042
      • Northwell Health/Monter Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Wexner Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women & Infants Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77030
      • Oncology Consultants- Texas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Arm 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 1 Arm 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 1 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 1 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 2 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 2 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 3 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 3 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 4 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 4 Rebastinib 100 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2
Experimental: Part 2 Cohort 5 Rebastinib 50 mg + Paclitaxel 80 mg/m^2; 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.	Drug: Rebastinib; Administered orally; Other Names: DCC-2036; Drug: Paclitaxel; Paclitaxel administered by IV infusion at 80 mg/m^2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Number of participants (pts) who experienced serious adverse events (SAE) and adverse events (AE).	Baseline up to 2.89 years
Objective Response Rate (ORR) (Part 2 Expansion)	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.	Baseline to PD or Death due to Any Cause (Up to 1.54 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (Part 1 Escalation)	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	Baseline to PD or Death due to Any Cause (Up to 0.92 years)
Duration of Response (DOR)	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 from CR or PR to PD or Death due to Any Cause (Up to 1.54 years)
Time to Progression (TTP)	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.	First Dose of Study Drug to PD (Up to 2.61 years)
Progression-free-survival (PFS)	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.	First Dose of Study Drug to PD or Death due to Any Cause (Up to 2.61 years)
Overall Survival (OS)	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.	First Dose of Study Drug to Death due to Any Cause (Up to 2.82 years)
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Rebastinib (Part 1)	Measure the Cmax	Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)
PK: Area Under the Concentration-time Curve (AUC) 0-6 Hours of Rebastinib (Part 1)	Measure the AUC 0-6 hours	Part 1: Cycle 1 Day 1 (C1 D1), C1 D15 (Cycle = 28 days)

Collaborators and Investigators

• Sponsor: Deciphera Pharmaceuticals, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Actual): May 23, 2022
• Study Completion (Actual): May 23, 2022

Study Registration Dates

• First Submitted: July 5, 2018
• First Submitted That Met QC Criteria: July 25, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; endometrial cancer; paclitaxel; ovarian cancer; rebastinib; gynecological carcinosarcoma; malignant mixed Mullerian tumor (MMMT)
• Additional Relevant MeSH Terms: Neoplasms; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Rebastinib; Paclitaxel
• Other Study ID Numbers: DCC-2036-01-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No