Study of the Pan-DAC Inhibitor AR-42 and Pazopanib in Advanced Sarcoma and Kidney Cancer

NCT02795819 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: MCC-14-10774NCI-2016-00851P30CA016059
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Renal Cell Carcinoma; Soft Tissue Sarcoma; Metastatic Disease

Outcome Measures

Primary Outcomes (1)

• The Recommended Phase 2 Doses (RP2Ds) of AR-42 and Pazopanib When Given in Combination.

  To determine the recommended phase 2 doses (RP2Ds) for AR-42 and pazopanib that are the same as or less than the maximum tolerated doses (MTDs). The dose-limiting toxicity (DLT) evaluation period will be the first treatment cycle. Patients must have taken a minimum of 6 AR-42 doses and a minimum of 21 pazopanib doses during cycle 1 to be considered evaluable for DLT, if DLT has not been observed at the delivered dose. Patients' treatment dose level, dose modification, evaluability for DLT, and DLTs will be listed and summarized by basic descriptive statistics such as frequency and proportion. The maximum tolerated dose(MTDs)/recommended phase 2 doses (RP2Ds) will be found based on the criteria in the protocol.

  1 month

Secondary Outcomes (2)

• Number of Participants With Adverse Events That Were Related to Treatment, AR-42 and Pazopanib Combination.

  5 months

• The Antitumor Effects of the AR-42 and Pazopanib Treatment Regimen in Patients With Advanced Renal Cell Carcinoma (RCC) or Soft Tissue Sarcoma (STS).

  5 months

Study Arms (7)

Cohort minus 1 (-1)

EXPERIMENTAL

Participants take 10 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Cohort 1

EXPERIMENTAL

Participants take 20 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Cohort 2

EXPERIMENTAL

Participants take 20 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Cohort 3A

EXPERIMENTAL

Participants take 30 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Cohort 3B

EXPERIMENTAL

Participants take 30 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Cohort 4A

EXPERIMENTAL

Participants take 40 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 800mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Cohort 4B

EXPERIMENTAL

Participants take 40 mg AR-42 orally per day on 3 non-consecutive days during the 1st 3 weeks of each 4-week cycle and pazopanib 600mg orally daily continuously

Drug: AR-42; Drug: Pazopanib

Interventions

AR-42 DRUG

AR-42 tablets were taken orally once per day on 3 non-consecutive days during the first 3 weeks of each 4-week cycle. If treatment was interrupted during the cycle, the cycle was to be extended

Also known as: HDAC-42, OSU-HDAC42

Cohort 1; Cohort 2; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 4B; Cohort minus 1 (-1)

Pazopanib DRUG

Pazopanib tablets were taken orally once daily continuously during each 4-week treatment cycle. There were no scheduled breaks in pazopanib therapy

Also known as: Votrient

Cohort 1; Cohort 2; Cohort 3A; Cohort 3B; Cohort 4A; Cohort 4B; Cohort minus 1 (-1)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Recurrent, unresectable, or metastatic Renal Cell Carcinoma (RCC) or Soft Tissue Sarcoma (STS) (any histologic type) for which pazopanib was an appropriate therapy
• Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
• Age ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate bone marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1200/mm3
• Platelets ≥ 120,000/mm3
• Hemoglobin ≥ 9.5 g/dL
• Adequate renal function as defined below:
• Creatinine ≤ 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance ≥ 60 mL/min
• Proteinuria ≤ 2+ \[100 mg/dL\] (using a random urine sample or \< 3.0 gm using a 24-hour sample) (Note: If urine sample indicates ≥ 2+ \[100 mg/dL\]), a 24-hour urine sample must be collected and tested; urine protein in the 24-hour sample must be \< 3.0 gm/24 hours.)
• Adequate hepatic function as defined below:
• Total bilirubin ≤ 1.5 x ULN for the laboratory (Note: Patients with known Gilbert's Syndrome were not eligible for this study)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN for the laboratory
• Alanine aminotransferase (ALT) ≤ 2.5 x ULN for the laboratory

You may not qualify if:

• Symptomatic or untreated brain metastasis
• Leptomeningeal metastasis
• Any investigational agent within 4 weeks prior to initiating study treatment
• Previous therapy with pazopanib
• Inability to swallow medication
• Known or suspected malabsorption condition or obstruction
• Contraindication to antiangiogenic agents, including:
• Serious non-healing wound, non-healing ulcer, or bone fracture
• Major surgical procedure or significant traumatic injury within 4 weeks prior to initiating study treatment; other surgical procedures within 2 weeks prior to initiating study treatment
• Pulmonary hemorrhage/bleeding event ≥ grade 2 within 12 weeks prior to initiating study treatment
• Any other hemorrhage/bleeding event ≥ grade 3 within 12 weeks prior to initiating study treatment
• History of organ allograft including corneal transplant
• Evidence of bleeding diathesis or coagulopathy
• Documented Gilbert's Syndrome
• Resting systolic blood pressure (BP) \< 100 mmHg

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Sarcoma; Neoplasm Metastasis

Interventions

HDAC-42; pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Neoplasms, Connective and Soft Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Incomplete objectives due to early termination of trial.

Results Point of Contact

• Title: Andrew Poklepovic, MD
• Organization: Virginia Commonwealth University Massey Cancer Center

AskMassey@vcu.edu

877-462-7739

Study Officials

• Andrew S Poklepovic, MD

  Massey Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2016
• First Posted: June 10, 2016
• Study Start: July 8, 2016
• Primary Completion: November 24, 2016
• Study Completion: March 14, 2019
• Last Updated: October 24, 2019
• Results First Posted: October 24, 2019

Record last verified: 2019-10

Locations

US (1)