Clinical Trials Logo

Clinical Trial Summary

This phase 1 study was developed to identify recommended phase 2 doses (RP2Ds) of AR-42 and pazopanib when given in combination for subsequent clinical trials and may have potentially identified candidate pharmacodynamic and predictive biomarkers.


Clinical Trial Description

This study was a single-arm, open-label, dose escalation phase 1 trial to determine the RP2Ds of AR-42 and pazopanib when given in combination to patients with advanced Renal Cell Carcinoma (RCC) or Soft Tissue Sarcoma (STS). Eligible patients had recurrent, unresectable, or metastatic RCC or STS for which pazopanib was an appropriate therapy.

AR-42 was taken orally once per day on 3 non-consecutive days each week during the first 3 weeks of each 4-week cycle. Pazopanib was taken by mouth once daily continuously during each cycle.

A modified 3+3 dose-escalation design was to be followed until the maximum tolerated doses (MTDs) were determined. The initial cohort of patients were assigned to an AR-42 dose of 20 mg taken once per day on 3 non-consecutive days during the first 3 weeks of each 4-week cycle and a pazopanib dose of 600 mg once daily continuously. Additional patients would be enrolled until a total of 12 patients were treated at the MTDs.

The protocol specifies a dose escalation plan that initially impacts only the pazopanib dose. The starting dose of pazopanib (600 mg) was planned to be escalated early so that the FDA-approved full dose of pazopanib (800 mg) would be reached before escalating the AR-42 dose. In subsequent dose-escalation steps, the dose of AR-42 was planned to be increased in 10-mg increments from a starting dose of 20 mg to a maximum dose of 40 mg.

If the number of Dose-Limiting Toxicities (DLT) showed that the MTD was exceeded with a pazopanib dose of 800 mg , the pazopanib dose was planned to be decreased to 600 mg and the AR-42 dose increased in 10-mg increments regardless of relationship of the DLT to one or both study medications.

Toxicities were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0). The DLT evaluation period was the first treatment cycle. A minimum of 6 doses of AR-42 and 21 doses of pazopanib were required for a patient to be DLT-evaluable (if DLT was not observed with the delivered dose). DLT was defined as any ≥ grade 3 toxicity occurring during the DLT evaluation period and attributed to one or both of the study medications EXCEPT the following:

- The first incidence of grade 3 PPE at any dose level (subsequent incidences of grade 3 PPE will be considered DLT)

- Grade 3 nausea and vomiting in the absence of adequate prophylaxis and/or responsive to medical management within 48 hours

- Grade 3 diarrhea in the absence of adequate prophylaxis and/or responsive to medical management within 48 hours

- Grade 3 fatigue responsive to medical management • Grade 3 asymptomatic hypertension lasting ≤ 7 days

- Grade 3 electrolyte abnormalities that are corrected within 48 hours and, when corrected, can be maintained

- Grade 3 asymptomatic lipase elevation lasting ≤ 7 days

- Grade 3 decrease in platelet count if no clinically significant hemorrhage has occurred

- Grades 3 and 4 decrease in white blood cell count

- Grade 3 decrease in neutrophil count

- Grade 4 decrease in neutrophil count lasting ≤ 7 days

- Grades 3 and 4 decrease in lymphocyte count

Dose escalation was planned to continue until the maximum-tolerated dose (MTD), defined as one dose level below the dose in which dose-limiting toxicities (DLTs) are observed in >1 of the participants (e.g., in at least 2 participants in a cohort of at least 3). In the cohort of 12 patients at the MTD, no more than 3 DLTs were allowed to confirm the MTD. The RP2D was defined as equal to or less than the MTD, with an allowance to consider an RP2D below the MTD given the overall tolerability of the regimen including the frequency of AEs that were not DLTs and the frequency of dose modifications. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02795819
Study type Interventional
Source Virginia Commonwealth University
Contact
Status Terminated
Phase Phase 1
Start date July 8, 2016
Completion date March 14, 2019

See also
  Status Clinical Trial Phase
Active, not recruiting NCT04987203 - Study to Compare Tivozanib in Combination With Nivolumab to Tivozanib Monotherapy in Subjects With Renal Cell Carcinoma Phase 3
Recruiting NCT06391879 - Establishment of a Multidimensional Prediction Model for the Natural Course of VHL Disease-related Renal Cell Carcinoma
Completed NCT02526017 - Study of Cabiralizumab in Combination With Nivolumab in Patients With Selected Advanced Cancers Phase 1
Recruiting NCT05059444 - ORACLE: Observation of ResiduAl Cancer With Liquid Biopsy Evaluation
Terminated NCT03655613 - APL-501 or Nivolumab in Combination With APL-101 in Locally Advanced or Metastatic HCC and RCC Phase 1/Phase 2
Active, not recruiting NCT03170960 - Study of Cabozantinib in Combination With Atezolizumab to Subjects With Locally Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Withdrawn NCT05418387 - A Social Support Intervention to Improve Treatment Among Hispanic Kidney and Liver Cancer Patients in Arizona N/A
Recruiting NCT04623502 - An Investigation of Kidney and Urothelial Tumor Metabolism in Patients Undergoing Surgical Resection and/or Biopsy N/A
Completed NCT02853344 - Study of Pembrolizumab (MK-3475) Monotherapy in Locally Advanced/Metastatic Renal Cell Carcinoma (MK-3475-427/KEYNOTE-427) Phase 2
Terminated NCT04088500 - A Study of Combination Nivolumab and Ipilimumab Retreatment in Patients With Advanced Renal Cell Carcinoma Phase 2
Completed NCT05070637 - Circulating Tumor Cell Reducing No-touch Nephrectomy N/A
Active, not recruiting NCT03634540 - A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003) Phase 2
Not yet recruiting NCT06049030 - A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma Phase 1
Completed NCT03652077 - A Safety and Tolerability Study of INCAGN02390 in Select Advanced Malignancies Phase 1
Completed NCT01358721 - Phase I Biomarker Study (BMS-936558) Phase 1
Active, not recruiting NCT04503148 - Anesthesia and Cancer Study: Renal Cell Carcinoma N/A
Completed NCT02386826 - INC280 Combined With Bevacizumab in Patients With Glioblastoma Multiforme Phase 1
Not yet recruiting NCT05808608 - A Study of AK104 Plus Axitinib in Advanced/Metastatic Special Pathological Subtypes of Renal Cell Carcinoma Phase 1/Phase 2
Withdrawn NCT03323710 - Study of Propranolol Plus Sunitinib in First-line Treatment of Metastatic Renal Cell Carcinoma Phase 2
Completed NCT03052504 - Prospective Versus Retrospective Complications in Radical Cystectomy and Nephrectomy