Pemetrexed, Cisplatin With Soft Tissue Sarcoma (ALBATROSS)

A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Pemetrexed/Cisplatin Chemotherapy for Patients With Metastatic/Recurrent Soft Tissue Sarcoma in 4- Independent Histologic Subtypes

Soft tissue sarcoma (STS) is rare malignancy of mesodermal origin, representing less than 1% of all malignant neoplasms. They are a group of diseases encompassing diverse histological subtypes with very different biomorphologies, prognoses, and responses to treatments. At advanced stages of STS, anticancer treatments are less effective and the prognosis is poor with a median survival of 8 to 18 months. Doxorubicin and ifosfamide given each alone or in their combination have represented the mainstream of anticancer treatments in metastatic STS. However, salvage treatments for patients with progression after doxorubicin/ifosfamide-based treatment are limited and anticancer agents such as gemcitabine/docetaxel, pazopanib, eribulin and trabectedin are currently used as a standard of care (SOC).

For metastatic sarcoma, a study of pemetrexed alone in patients with refractory STS who have progressed after doxorubicin and/or ifosfamide-based anticancer treatment was conducted. In this study including 48 patients, most of whom had relatively poor course of disease with disease progression after the 2nd- and/or 3rd-line treatment, pemetrexed was well tolerated and associated with 5% of response rate and 33% of 3-month progression-free rates suggesting potential antitumor efficacy with good tolerability profile with refractory STS.

However, as conventional agents have showed different efficacy depending on various subtypes of STS, a confirmatory study to see clinical utilities of a given regimen by subtype is required also for pemetrexed/cisplatin. Therefore, the investigators intend to proceed this phase 2 clinical trial to evaluate the efficacy and safety of pemetrexed/cisplatin combination therapy in patients with advanced/metastatic STS who received up to two-lines of prior palliative anticancer treatments with histological subtype-specific cohorts (leiomyosarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and others) in order to provide a basis for a subsequent phase 3 study by selecting histological subtype(s) in which the efficacy of study regimen is to be proven.

Study Overview

• Status: Recruiting
• Conditions: Sarcoma,Soft Tissue
• Intervention / Treatment: Drug: pemetrexed+cisplatin

• Study Type: Interventional
• Enrollment (Anticipated): 164
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hyo Song Kim, MD, Ph.D; Phone Number: 82-2-2228-8124; Email: hyosong77@yuhs.ac

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Severance Hospital
    • Contact: Hyo Song Kim, Ph.D; Email: hyosong77@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• histologically confirmed, advanced/metastatic STS
• Is ≥ 19 years of age
• Eastern Cooperative Oncology Group performance status of 0 or 1
• measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1
• laboratory values indicating adequate organ function
• a documented postmenopausal woman, or is a premenopausal woman with negative urine or serum pregnancy test
• life expectancy ≥ 12 weeks

Exclusion Criteria:

• previously received more than 2 regimens of cytotoxic chemotherapy
• received chemotherapy, surgery to major organ, or radiotherapy within the last 2 weeks
• ongoing toxicity (≥ CTCAE grade 2) from previous anticancer therapy
• central nervous system (CNS) metastases requiring active treatment
• diagnosis of second malignancy or has a history of active malignancy within the past 3 years
• other medical conditions where the study treatment is intolerable
• history of active infection
• hypersensitivity to pemetrexed or any of its excipients
• Co-administration with yellow fever vaccine
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: pemetrexed+cisplatin; Pemetrexed 500 mg/m2 (Day 1) and cisplatin 75 mg/m2 (Day 1) will be given via intravenous (IV) infusion. Each cycle consists of 21 days, and this combination therapy will be continued until Cycle 6. Starting from Cycle 7, pemetrexed alone will be administered every 3 weeks (Q3W) as IV infusion until disease progression.

Drug: pemetrexed+cisplatin; Pemetrexed 500 mg/m2 (Day 1) and cisplatin 75 mg/m2 (Day 1) will be given via intravenous (IV) infusion. Each cycle consists of 21 days, and this combination therapy will be continued until Cycle 6. Starting from Cycle 7, pemetrexed alone will be administered every 3 weeks (Q3W) as IV infusion until disease progression. Vitamin B12 1000 mcg intramuscular (IM) injection will be given within 14 days prior to the first dose of pemetrexed, every 9 weeks (on the same day as study treatment) thereafter, and then 21 days after the last dose of pemetrexed. Folic acid 1 mg will be administered daily starting from 14 days before the first dose of pemetrexed and continued until 21 days after the last dose of pemetrexed. Study treatment will be continued until PD, unacceptable AE, or decision to discontinue by subject or physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) rate	Progression-free survival rate at Week 12 (PFR 12) based on RECIST 1.1	at 12 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
overall response rate	every 6 weeks, up to 52 weeks

Collaborators and Investigators

• Sponsor: Yonsei University

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 22, 2020
• Primary Completion (ANTICIPATED): November 1, 2022
• Study Completion (ANTICIPATED): November 1, 2022

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (ACTUAL): October 28, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 22, 2021
• Last Update Submitted That Met QC Criteria: April 20, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Cisplatin; Pemetrexed
• Other Study ID Numbers: 4-2019-0923

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No