Pazopanib in Combination With PCI-24781 in Patients With Metastatic Solid Tumors

NCT01543763 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 11955NCI-2012-01142
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This is a open-label non-randomized, dose escalation and expansion Phase Ia/Ib study to determine the safety, tolerability and maximum tolerated dose (MTD) of pazopanib in combination with PCI-24781 in patients with advanced solid tumors.

Conditions

Metastatic Solid Tumors

Keywords

metastatic; solid; sarcoma; progression

Outcome Measures

Primary Outcomes (2)

• Dose limiting toxicity (DLT)

  A dose limiting toxicity (DLT) will be defined as any predetermined adverse events occurring during Cycle 1 when association to therapy that is part of this study is related or possibly related

  up to 4 weeks

• Maximum Tolerated Dose (MTD)

  The maximum tolerated dose (MTD) will be defined as the highest tested dose level at which less than 33% of patients experience DLT in Cycle 1

  up to 4 weeks

Secondary Outcomes (10)

• Establish the volume of distribution of PCI-24781, pazopanib and the combination of the two drugs.

  up to 2 months

• Establish the bioavailability of PCI-24781, pazopanib and the combination of the two drugs.

  up to 2 months

• Establish the clearance of PCI-24781, pazopanib and the combination of the two drugs.

  up to 2 months

• Establish the half-life of PCI-24781, pazopanib and the combination of the two drugs.

  up to 2 months

• Establish the area under the curve (AUC) of PCI-24781, pazopanib and the combination of the two drugs.

  up to 2 months

Study Arms (1)

Panobinostat with PC124871

EXPERIMENTAL

Drug: PZP115891, PCI-24781

Interventions

PZP115891, PCI-24781 DRUG

PCI-24781: oral, 30 to 75 mg/m2 b.i.d. Cycle 1, Days -7 to -4 and Cycle 1 and ongoing - Days 1-5, 8-12, 15-19 PZP115891: oral, 400 - 800 mg qd 28 days per cycle

Also known as: abexinostat, S 78454, GW786034, Votrient™, Pazopanib

Panobinostat with PC124871

Eligibility Criteria

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

You may qualify if:

• Patients must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to adhere with treatment and followup.
• Age ≥ 18 years
• Phase Ia: Patients must have histologically or cytologically documented metastatic solid tumor malignancies. Phase Ib: Patients must have histologically or cytologically confirmed locally advanced, solid tumor malignancies of one of the following tumor types:
• Renal cell carcinoma (N = 20 patients) (Cohort A)
• Non-anaplastic thyroid carcinoma (N = 20 patients) (Cohort B) Documentation of histology from a primary or metastatic site is allowed.
• Soft tissue sarcoma (N = 20 patients) (Cohort C). Patients must have progressed in a prior line of therapy.
• Ovarian carcinoma (N = 20 patients) (Cohort D)
• Measurable disease by RECIST 1.1
• Phase Ia: Patients may have de novo metastatic disease, or documented progression despite any number of prior therapies. Patients must have no curative or other effective therapeutic options available. Phase Ib: Patients may have had any number of prior treatments, or prior pazopanib.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Resolution of all chemotherapy or radiation-related toxicities to Grade 1 severity or lower except for alopecia
• Patient must be at least 4 weeks or five half-lives (whichever is shorter) from last standard or experimental therapy, except Patients who have received prior pazopanib are eligible but must not have received it in the last two weeks.
• Patients must be at least 28 days from last radiation therapy dose, Peptide Receptor Radionuclide Therapy (PRRT), surgery, or tumor embolization prior to the first dose of pazopanib/PCI-24781
• A female is eligible to enter and participate in this study if she is of:
• Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had:

You may not qualify if:

• Concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN (upper limit of normal) are not permitted.
• If UPC ≥1, then a 24-hour urine protein must be assessed. Subjects must have a 24-hour urine protein value \<1 g to be eligible.
• Patients with other primary malignancies receiving active treatment at the time of study entry, other than carcinoma in situ of the cervix, non-melanoma skin cancer, nonmuscle invasive bladder cancer.
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases.
• Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel.
• Presence of known active hepatitis C viral (HCV) or active hepatitis B viral (HBV) infection, history of human immunodeficiency virus (HIV), or other uncontrolled systemic infection
• Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• Concurrent use of medications that are known to prolong or cause QT prolongation

Sponsors & Collaborators

• Pamela Munster: lead
• Pharmacyclics LLC.: collaborator
• Novartis: collaborator
• Xynomic Pharmaceuticals, Inc.: collaborator
• GlaxoSmithKline Research and Education Foundation for Cardiovascular Disease: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Sarcoma; Disease Progression

Interventions

abexinostat; pazopanib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Disease Attributes

Study Officials

• Pamela Munster, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Medicine (Hematology/Oncology), UCSF

Study Record Dates

• First Submitted: February 17, 2012
• First Posted: March 5, 2012
• Study Start: June 25, 2012
• Primary Completion: January 31, 2024
• Study Completion: December 31, 2024
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)