A Study of E7130 in Participants With Solid Tumors

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• Neoplasms 9,328

Keywords

• Solid tumors
• Squamous cell carcinoma of the head and neck
• Urothelial carcinoma

Eligibility criteria

Study arms

• Experimental
  E7130 (2-Week Regimen)

  Part 1 (Cycle 1; 28 days): The first cohort of 3 participants will receive 25 micrograms per meters squared (μg/m\^2) of E7130, on Day 1 and Day 15 as an intravenous infusion. If a drug-related Grade 2 or higher toxicity excluding clinically insignificant events is not observed in the initial cohort, dose-limiting toxicities (DLTs) will be evaluated in successive dose levels with single participants until such a toxicity is observed. Once the maximum tolerated dose (MTD) will be determined. Part 2: Participants with squamous cell carcinoma of the head and neck and urothelial carcinoma will be evaluated at the dose level determined in Part 1 in a 2-week or in a 3-week regimen based on the evaluations in Part 1.

  Drug: E7130

• Experimental
  E7130 (3-Week Regimen)

  Part 1 (Cycle 1; 21 days): On Day 1, participants will receive E7130 at (-1) a lower dose than the dose at which the first DLT was observed in the 2-week regimen. Once the MTD will be determined. Part 2: Participants with squamous cell carcinoma of the head and neck and urothelial carcinoma will be evaluated at the dose level determined in Part 1 in a 3-week or in a 2-week regimen based on the evaluations in Part 1.

  Drug: E7130

Interventions

• DrugE7130

  Starting dose of 25 μg/m\^2 on Day 1 and Day 15 of Cycle 1.

• DrugE7130

  Starting dose is lower than one at which the first DLT was observed in the 2-week regimen administered on Day 1 of Cycle 1.

Primary outcomes

1. Part 1: Number of participants assigned to the every 2 weeks regimen with dose-limiting toxicities (DLTs)

   DLTs are defined as study drug related adverse events (AEs). Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE 4.03).

   Time frame: Cycle 1 (28 days)

2. Part 1: Number of participants assigned to the every 3 weeks regimen with DLTs

   DLTs are defined as study drug related AEs. Toxicity will be evaluated according to NCI CTCAE 4.03.

   Time frame: Cycle 1 (21 days)

3. Part 1 and Part 2: Number of participants with adverse events (AEs)

   Time frame: Up to approximately 83 months

4. Part 1 and Part 2: Number of participants with any clinically significant clinical laboratory test value

   Clinical significance will be determined by the Investigator.

   Time frame: Up to approximately 83 months

5. Part 1 and Part 2: Number of participants with any clinically significant vital sign value

   Clinical significance will be determined by the Investigator.

   Time frame: Up to approximately 83 months

6. Part 1 and Part 2: Change from Baseline in arterial oxygen saturation

   Time frame: Baseline; Up to approximately 83 months

7. Part 1 and Part 2: Change from Baseline in body weight

   Time frame: Baseline; Up to approximately 83 months

8. Part 1 and Part 2: Number of participants with any clinically significant 12-lead electrocardiogram (ECG) value

   Time frame: Up to approximately 83 months

9. Part 1 and Part 2: Change from Baseline in the performance status (PS) score established by the Eastern Cooperative Oncology Group (ECOG)

   Time frame: Baseline; Up to approximately 83 months

Secondary outcomes

1. Part 1: Maximum Tolerated Dose (MTD) of E7130

   The MTD will be selected as the dose with the smallest difference between the target DLT rate of 25% and an estimate of DLT rate based on the posterior distribution of DLT rate for each dose.

   Time frame: Cycle 1 and Cycle 2 (56 days [every 2 weeks regimen] [each Cycle length = 28 days], 42 days [every 3 weeks regimen] [each Cycle length = 21 days])

2. Part 1: Maximum observed plasma concentration (Cmax) of E7130

   Cmax is the maximum observed concentration of E7130 after administration of the drug.

   Time frame: Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days)

3. Part 1: Time to reach maximum plasma concentration (Tmax) of E7130

   Tmax is the time at which the highest drug concentration occurs.

   Time frame: Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days)

4. Part 1: Area under the plasma concentration time curve (AUC) from time 0 to infinity

   Time frame: Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days)

5. Part 1: Terminal elimination phase half-life (t1/2) of E7130

   Time frame: Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days)

6. Part 1: Total clearance of E7130

   Time frame: Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days)

7. Part 1: Volume of distribution (Vd)

   Time frame: Bi-weekly: Cycles 1-2 Days 1 and 15: 0-168 hours post-infusion (each Cycle length=28 days); Tri-weekly: Cycles 1-2 Day 1: 0-336 hours post-infusion (each Cycle length=21 days)

8. Part 1 and Part 2: Recommended dose for future studies

   The recommended dose will be determined based on the on the MTD, the optimal biologic dose, and efficacy/safety/pharmacokinetic/pharmacodynamic data in Part 1 and Part 2.

   Time frame: Up to approximately 83 months

9. Part 1 and Part 2: Number of participants with advanced solid tumors with anti-tumor activity

   Time frame: Up to approximately 83 months

10. Part 1 and Part 2: Best Overall Response (BOR)

    The BOR will be based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. BOR is defined as complete response (CR), partial response (PR), stable disease (SD), progression of disease (PD), and not evaluable (NE), where SD has to be achieved at ≥5 weeks after the first dose.

    Time frame: Up to approximately 83 months

11. Part 1 and Part 2: Objective Response Rate (ORR)

    The ORR is defined as the percentage of participants with a BOR of CR or PR.

    Time frame: Up to approximately 83 months

12. Part 1 and Part 2: Disease Control Rate (DCR)

    DCR is defined as the percentage of participants with a BOR of CR, PR, or SD.

    Time frame: Up to approximately 83 months

13. Part 1 and Part 2: Clinical Benefit Rate (CBR)

    The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD ≥23 weeks).

    Time frame: Up to approximately 83 months

14. Part 2: Progression-free survival (PFS)

    PFS is defined as the time from the date of the first dose to the first documented date of the event (disease progression or death from any cause, whichever occurs first).

    Time frame: Up to approximately 83 months

15. Part 2: Overall Survival (OS)

    OS is defined as the time from the date of the first dose to the date of death from any cause.

    Time frame: Up to approximately 83 months