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History of Changes for Study: NCT03601897
A Safety, Tolerability and PK Study of Rebastinib in Patients With Advanced Solid Tumors
Latest version (submitted September 29, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 25, 2018 None (earliest Version on record)
2 September 17, 2018 Outcome Measures, Arms and Interventions, Study Status, Study Design, Study Identification, Eligibility, Conditions and Study Description
3 September 18, 2018 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 October 12, 2018 Study Status and Contacts/Locations
5 May 13, 2019 Study Status, Contacts/Locations, Eligibility and Arms and Interventions
6 June 24, 2019 Study Status and Contacts/Locations
7 July 17, 2019 Contacts/Locations and Study Status
8 July 24, 2019 Contacts/Locations and Study Status
9 September 13, 2019 Study Status and Contacts/Locations
10 November 1, 2019 Study Status and Contacts/Locations
11 March 27, 2020 Study Status, Contacts/Locations, Outcome Measures, Eligibility, Arms and Interventions, Study Design and Conditions
12 June 11, 2020 Study Status and Contacts/Locations
13 October 22, 2020 Contacts/Locations and Study Status
14 November 4, 2020 Study Status and Contacts/Locations
15 March 31, 2021 Contacts/Locations and Study Status
16 June 9, 2021 Arms and Interventions and Study Status
17 September 29, 2021 Recruitment Status, Contacts/Locations and Study Status
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Study NCT03601897
Submitted Date:  July 25, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: DCC-2036-01-003
Brief Title: A Safety, Tolerability and PK Study of Rebastinib in Patients With Advanced Solid Tumors
Official Title: An Open-Label, Multicenter, Phase 1b Study of Rebastinib (DCC-2036) in Combination With Paclitaxel to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced or Metastatic Solid Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2018
Overall Status: Not yet recruiting
Study Start: August 1, 2018
Primary Completion: June 1, 2019 [Anticipated]
Study Completion: July 1, 2020 [Anticipated]
First Submitted: July 5, 2018
First Submitted that
Met QC Criteria:
July 25, 2018
First Posted: July 26, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
July 25, 2018
Last Update Posted: July 26, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Deciphera Pharmaceuticals LLC
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: This is an open-label Phase 1b 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:
Open or close this module Conditions
Conditions: Locally Advanced or Metastatic Solid Tumor
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Randomized
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: 50 mg rebastinib Arm
50 mg BID of rebastinib orally (PO) in combination with paclitaxel administered by IV infusion at 80 mg/m2 in repeated 28-day cycles.
Drug: rebastinib
25 mg tablets or 75 mg tablets
Other Names:
  • DCC-2036
Drug: Paclitaxel
Paclitaxel administered by IV infusion at 80 mg/m2
Experimental: 100 mg rebastinib Arm
100 mg BID of rebastinib orally (PO) in combination with paclitaxel administered by IV infusion at 80 mg/m2 in repeated 28-day cycles. If 100 mg BID is deemed intolerable, a cohort of 75 mg BID in combination with paclitaxel will be initiated
Drug: rebastinib
25 mg tablets or 75 mg tablets
Other Names:
  • DCC-2036
Drug: Paclitaxel
Paclitaxel administered by IV infusion at 80 mg/m2
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Incidence of Adverse Events
[ Time Frame: Approximately 24 months ]

Identify the observed adverse events, serious adverse events and discontinuation of study drug due to toxicity to inform determination of recommended phase 2 dose
Secondary Outcome Measures:
1. Time to maximum observed concentration at steady state (Tmax,ss) of rebastinib
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the time to maximum observed concentration at steady state
2. Maximum observed concentration (Cmax) of rebastinib
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the Cmax
3. Maximum observed concentration at steady state of rebastinib
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the maximum observed concentration at steady state
4. Concentration observed at the end of the dosing interval (Cmin) of rebastinib in combination with paclitaxel
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the concentration observed at the end of the dosing interval
5. Concentration observed at the end of the dosing interval at steady state (Cmin, ss) of rebastinib in combination with paclitaxel
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the concentration observed at the end of the dosing interval at steady state
6. Area under the concentration-time curve (AUC) of rebastinib in combination with paclitaxel
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the AUC
7. Half-life (T1/2) of rebastinib in combination with paclitaxel
[ Time Frame: Cycle 1 Day 1 (each cycle is 28 days), Cycle 1 Day 15, ≥ Cycle 2 Day 1 (at the following time points: pre-dose; 1, 2, 4, 6, hours post-dose; and pre- and post- paclitaxel infusion) through study completion ]

Measure the half-life
8. Objective response rate (ORR)
[ Time Frame: at 8 weeks of the combination therapy, and in the event of disease progression ]

Objective response rate as determined by confirmed CR + confirmed PR
9. Disease control rate (DCR)
[ Time Frame: at 8 weeks of the combination therapy, and in the event of disease progression ]

DCR as determined by complete response [CR] + partial response [PR] + stable disease
10. Time to best response
[ Time Frame: Approximately 24 months ]

Measure of time from Cycle 1 Day 1 to PR or CR
11. Progression-free-survival (PFS)
[ Time Frame: Approximately 24 months ]

Measure of the time from Cycle 1 Day 1 to disease progression or death due to any cause
12. Time to progression (TTP)
[ Time Frame: Approximately 24 months ]

Measure of the time from Cycle 1 Day 1 to the first documentation of progressive disease
13. Duration of response (DOR)
[ Time Frame: Approximately 24 months ]

Measure of time from PR, CR to disease progression or death due to any cause
14. Overall survival (OS)
[ Time Frame: Approximately 24 months ]

Measure of overall survival
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Male or female patients ≥18 years of age at the time of informed consent.
  2. Histologically confirmed diagnosis of a locally advanced or metastatic solid tumor for which paclitaxel or nab-paclitaxel are considered appropriate treatment.

    i. Patients must have received all other approved therapies available to them.

  3. ECOG PS of ≤2.
  4. Able to provide an archival tumor tissue sample; if an archival tumor tissue sample is unavailable, a fresh tumor biopsy is required prior to the first dose of study drug.
  5. Adequate organ function and bone marrow reserve as indicated by the following laboratory assessments performed within 14 days prior to the first dose of study drug:

    i. Bone marrow function: absolute neutrophil count (ANC) ≥1500/µL; hemoglobin ≥9 g/dL; platelet count ≥100,000/µL.

    ii. Hepatic function: total bilirubin ≤1.5× the upper limit of normal (ULN) or < 3× ULN for Gilbert's syndrome; aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5× ULN (≤5× ULN in the presence of hepatic metastases).

    iii. Renal function: serum creatinine ≤1.5× ULN or creatinine clearance ≥30 mL/min based either on urine collection or Cockcroft Gault estimation.

    iv. Coagulation profile: prothrombin time adjusted for the international normalized ratio (PT-INR) and partial thromboplastin time (PTT) ≤1.5× ULN. Patients on a stable, maintenance regimen of anticoagulant therapy for at least 30 days prior to study drug administration may have PT-INR measurements >1.5× ULN if, in the opinion of the Investigator, the patient is suitable for the study. An adequate rationale must be provided to the Sponsor prior to enrollment.

  6. If a female of childbearing potential, must have a negative serum beta-human chorionic gonadotropin (β-hCG) pregnancy test at screening, a negative urine or serum pregnancy test at Cycle 1 Day 1 (Baseline), and agree to use two methods of contraception, with one of them being highly effective, prior to the first dose of study drug and for at least 120 days following the last dose of study drug.
  7. If male, must agree to use two methods of contraception, with one of them being highly effective, and refrain from sperm donation prior to the first dose of study drug through 120 days following the last dose of study drug.
  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 14 days or 5× the half-life (whichever is longer) prior to the first dose of the combination. For prior biological therapies, e.g., monoclonal antibodies, with a half-life longer than 3 days, the interval must be at least 28 days prior to the first dose of study drug.
  2. Not recovered from all toxicities from prior therapy to Grade ≤1 (or baseline) within 1 week prior to first dose of study drug (excluding alopecia and ≤Grade 3 clinically asymptomatic alkaline phosphatase).
  3. Peripheral neuropathy of any etiology >Grade 1.
  4. Patients with a prior or concurrent malignancy whose natural history or treatment have the potential to interfere with the safety or efficacy assessment of this clinical trial.
  5. Known active CNS metastases defined as:

    i. Unstable (i.e., evidence of progression by magnetic resonance imaging [MRI]) within 4 weeks prior to the first dose of study drug.

    ii. Neurologic symptoms within 2 weeks prior to the first dose of study drug and required use of enzyme-inducing antiepileptic drugs.

    iii. Patients who require steroids must be on a stable dose for 2 weeks prior to the first dose of study drug.

  6. Use of systemic corticosteroids within 7 days prior to the first dose of study treatment or an existing condition that requires the concomitant use during the course of the study, unless the dose is no more than the equivalent of prednisone 15 mg/day.
  7. Known retinal neovascularization, macular edema or macular degeneration.
  8. History or presence of clinically relevant cardiovascular abnormalities such as uncontrolled hypertension, (defined as systolic blood pressure ≥150 and/or diastolic blood pressure ≥95 mmHg), history of class III or IV congestive heart failure according to New York Heart Association classification, unstable angina or poorly controlled arrhythmia as determined by the Investigator, or myocardial infarction within 6 months prior to the first dose of study drug.
  9. QT interval corrected for heart rate at screening using Fridericia's formula (QTcF) >450 ms in males or >470 ms in females or history of QT interval corrected for heart rate (QTc) prolongation.
  10. Left ventricular ejection fraction (LVEF) <50% at screening.
  11. Arterial thrombotic or embolic events such as cerebrovascular accident (including ischemic attacks or pulmonary embolism) or hemoptysis within 6 months prior to the first dose of study drug.
  12. Venous thrombotic event (e.g., deep vein thrombosis) within the 3 months prior to the first dose of study drug; following a venous thrombotic event of ≥3 months prior to the first dose of study drug, must be on a stable dose of anticoagulation therapy.
  13. Active infection ≥Grade 3 requiring IV anti-infective treatment within 7 days prior to the first dose of study drug.
  14. Known human immunodeficiency virus or hepatitis C infection only if the patient is taking medications that are excluded per protocol, active hepatitis B, or active hepatitis C infection.
  15. Use of proton pump inhibitors (PPI) within 4 days prior to the first dose of study drug or an existing condition that requires the concomitant use of a proton pump inhibitor during the course of the study.
  16. If female, the patient is pregnant or lactating.
  17. Major surgery 4 weeks prior to the first dose of study drug; following major surgeries >4 weeks prior to the first dose of study drug, all surgical wounds must be healed and free of infection or dehiscence.
  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, such as uncontrolled pulmonary disease, active infection, or any other condition which, in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
Open or close this module Contacts/Locations
Central Contact Person: Clinical Trials
Telephone: 785-830-2100
Email: clinicaltrials@deciphera.com
Locations: United States, Alabama
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States, 35233
United States, Connecticut
Yale Cancer Center
New Haven, Connecticut, United States, 06510
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Oklahoma
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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