Nab-Sirolimus and Pazopanib Hydrochloride in Treating Patients With Advanced Nonadipocytic Soft Tissue Sarcomas

NCT03660930 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: RG171805310015NCI-2018-01624
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of nab-sirolimus and how well it works when given together with pazopanib hydrochloride in treating participants with nonadipocytic soft tissue sarcomas that has spread to other places in the body (advanced). Nab-sirolimus and pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Soft Tissue Sarcoma; Locally Advanced Soft Tissue Sarcoma; Metastatic Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (5)

• The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Nab-Rapamycin Dose

  Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.

  First 2 cycles (3-week cycles, 21 days each)

• The Maximum-tolerated Dose (MTD) of Nab-rapamycin in Combination With Pazopanib (Phase I) - Pazopanib Dose

  Will be estimated using dose-limiting toxicities (DLTs). Will use a Simon's minimax design.

  First 2 cycles (3-week cycles, 21 days each)

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  A DLT is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-sirolimus and pazopanib. Only toxicities with a clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic AE of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.

  First 2 cycles (3-week cycles, 21 days each)

• Dose Limiting Toxicities

  A Dose-limiting toxicity is defined as any Grade 3 or greater adverse event (AE), at least possibly related to either or both nab-Sirolimus or pazopanib. Only toxicities with clearly identified and documented alternative explanation may be deemed non-DLT. Dose-limiting toxicities include any death not clearly due to underlying disease or extraneous causes, or persistent intolerable nonhematologic Ae of any grade that requires dose reduction or permanent discontinuation of the study drug, in the opinion of the investigator.

  First 2 cycles (3 week cycles, 21 days each)

• Progression-free Survival (PFS) Rate

  Will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 where progression is defined as a 20% increase in the sum of the longest diameter of target lesions where the sum must also demonstrate an absolute increase of at least 5 mm, or the appearance of new lesions. Will be assessed via descriptive statistics.

  At 3 months

Secondary Outcomes (8)

• Incidence of Adverse Events Profile

  Up to 30 days after last dose (an average of 41 weeks)

• Median PFS

  At 6 months

• Progression-Free Survival Rate

  At 6 months

• Median Overall Survival (OS)

  At 12 months

• Overall Survival

  12 months

Study Arms (1)

Treatment (ABI-009, pazopanib)

EXPERIMENTAL

Participants receive nab-sirolimus intravenously (IV) on days 1 and 8 or day 1 only and pazopanib hydrochloride orally (PO) daily on days 1-21. Cycles repeat every 21 days until unequivocal clinical disease progression, unacceptable toxicity, or until in the opinion of the investigator the patient is no longer benefiting from therapy, or at the patient's discretion.

Drug: Sirolimus Albumin-bound Nanoparticles; Drug: Pazopanib hydrochloride

Interventions

Sirolimus Albumin-bound Nanoparticles DRUG

Given IV

Also known as: Nab-Rapamycin, Nanoparticle Albumin-Bound Rapamycin, ABI-009, Nanoparticle Albumin-bound Sirolimus, Fyarro, Sirolimus Protein-bound Particles

Treatment (ABI-009, pazopanib)

Pazopanib hydrochloride DRUG

Given PO

Also known as: Votrient

Treatment (ABI-009, pazopanib)

Eligibility Criteria

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

You may qualify if:

• Subjects, \>= 18 years old, must have a histologically confirmed diagnosis of non-adipocytic soft tissue sarcoma (STS) that is either metastatic or locally advanced and for which curative therapy is not available, surgery is not a recommended option, and pazopanib treatment is indicated.
• Subjects must have one or more measurable target lesions by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, assessed via computed tomography (CT) scan or magnetic resonance imaging (MRI).
• Clinical or radiological progression or failure due to toxicity on at least 1 prior regimen of systemic treatment for advanced disease. Subjects may not have received more than 4 prior lines of systemic therapy (no more than 2 prior therapies may be combination cytotoxic therapies). Neo-adjuvant/adjuvant/maintenance treatments are not included for this criterion.
• Last dose of prior therapy must have been completed a minimum of 14 days prior to start of protocol therapy. All ongoing toxicities related to prior therapy must be resolved or grade 1 (except alopecia).
• Total bilirubin =\< upper limit of normal (ULN) mg/dL (Subjects with known Gilbert's syndrome and a total bilirubin =\< 3 mg/dl are permitted to enroll to phase 2/expansion phase only with sponsor-investigator approval).
• Aspartate aminotransferase (AST) =\< 2.5 x ULN and alanine aminotransferase (ALT) =\< 2.5 x ULN.
• Serum creatinine =\<1.5 x ULN (If serum creatinine is \> 1.5 mg/dL, calculated creatinine clearance \> 50 mL/min using the Cockcroft-Gault formula may be included).
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L.
• Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L).
• Hemoglobin \>= 9 g/dL.
• Serum triglyceride =\< 300 mg/dL.
• Serum cholesterol =\< 350 mg/dL.
• Baseline cardiac left ventricular ejection fraction (LVEF) within institutional limits of normal (by echocardiogram or multigated acquisition \[MUGA\] study).
• Baseline electrocardiogram with corrected QT (QTc) \< 480 millisecond (Bazett's).
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

You may not qualify if:

• Soft tissue sarcomas with biology or defined treatments for which pazopanib is not indicated, including adipocytic STS, gastrointestinal stromal tumors (GIST), or Kaposi's sarcoma.
• Previously received an mTOR (mammalian target of rapamycin) inhibitor or angiogenesis inhibitor.
• Known active uncontrolled or symptomatic central nervous system (CNS) metastases. A subject with controlled and asymptomatic CNS metastases may participate in this study. As such, the patient must have completed any prior treatment for CNS metastases \>= 28 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
• Subjects with hemoptysis, central nervous system hemorrhage or gastrointestinal hemorrhage within the last 6 months prior to treatment are excluded due to pazopanib-associated risk of bleeding.
• Subjects with severe hepatic impairment and active gastrointestinal bleeding.
• Uncontrolled serious medical or psychiatric illness.
• Subjects with a currently active second malignancy other than non-melanoma skin cancers, carcinoma in situ of the cervix, resected incidental prostate cancer, or other adequately treated carcinoma-in-situ are ineligible. Subjects are not considered to have a currently active malignancy if they have completed therapy and are free of disease for \>= 1 year).
• Recent infection requiring systemic anti-infective treatment that was completed =\< 14 days prior to enrollment (with the exception of uncomplicated urinary tract infection or upper respiratory tract infection).
• No clinically significant gastrointestinal abnormalities including malabsorption syndrome, major resection of the stomach or small bowel that could affect the absorption of study drug, active peptic ulcer disease, inflammatory bowel disease, ulcerative colitis, 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.
• Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HbA1c) \> 8% despite adequate therapy.
• Subjects with unstable coronary artery disease, myocardial infarction, or an arterial thromboembolic event during preceding 6 months.
• Subjects with history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
• Use of strong inhibitors and inducers of CYP3A4 within the 14 days prior to receiving the first dose of nab-sirolimus. Additionally, use of any known CYP3A4 substrates with narrow therapeutic window (such as fentanyl, alfentanil, astemizole, cisapride, dihydroergotamine, pimozide, quinidine, terfenadine) within the 14 days prior to receiving the first dose of nab-sirolimus.
• Active hepatitis B or hepatitis C infection.
• Systemic immunosuppression, including human immunodeficiency virus (HIV) positive status with or without acquired immunodeficiency syndrome (AIDS).

Sponsors & Collaborators

• University of Washington: lead
• Aadi Bioscience, Inc.: collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Sarcoma

Interventions

pazopanib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Limitations and Caveats

While the study was originally designed as a phase I/II study, only the phase I component of the study was completed..

Results Point of Contact

• Title: Lee Cranmer, MD, PhD
• Organization: University of Washington

ldcranme@fredhutch.org

206-606-7439

Study Officials

• Lee Cranmer, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 4, 2018
• First Posted: September 7, 2018
• Study Start: April 1, 2019
• Primary Completion: November 17, 2022
• Study Completion: July 31, 2024
• Last Updated: April 30, 2025
• Results First Posted: March 13, 2024

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)