Camsirubicin + Pegfilgrastim to Determine MTD in ASTS

NCT05043649 | Terminated Phase 1 FDA Drug

• 1 other identifier: MNPR-201-001
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief Summary

This is an Interventional Study in Advanced Soft Tissue Sarcomas (ASTS). It is a Phase 1b, open-label, dose-escalation clinical study evaluating the safety of camsirubicin with prophylactic pegfilgrastim in the treatment of advanced soft tissue sarcomas. The objective of the study is to evaluate the safety of camsirubicin with prophylactic pegfilgrastim in the treatment of ASTS and determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of camsirubicin with prophylactic pegfilgrastim. The primary endpoint is the MTD (RP2D).The secondary endpoints are: safety profile of camsirubicin with prophylactic pegfilgrastim, PFS, TTP, ORR, DoR, OS and PK. As exploratory endpoint, Quality of life will be measured by using the Functional Assessment of Cancer Therapy: General (FACT-G).

Conditions

Advanced Soft-tissue Sarcoma

Keywords

Sarcoma; ASTS; Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (2)

• To determine Maximum Tolerated Dose (MTD)

  Adverse Events according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) will be collected for all treated subjects at each dose level of camsirubicin to identify dose limiting toxicities (DLTs). At each successive dose level, cohorts of 3 new patients will be entered if no dose limiting toxicity (DLT) is observed (3+3 design) within 21 days of initial dose. If a patient treated at any dose level experiences a DLT, a total of up to 6 patients will be treated at that dose level. Once two patients at any dose level experience a DLT, no additional patients will be treated at that level. The MTD will be defined as the highest dose level below the dose level at which 2 or more patients experience a DLT during the first 21 days from Cycle 1 Day 1.

  3 weeks after first injection

• Recommended Phase 2 Dose (RP2D) Camsirubicin HCl for Injection

  The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for the safety expansion cohort, based on safety, tolerability, efficacy, PK, and MTD data collected during the dose escalation portion of the study.

  Up to 1 year after the first dose

Secondary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events [Safety]

  Up to 1 year after the first dose

Study Arms (1)

Camsirubicin + pegfilgrastim

EXPERIMENTAL

Camsirubicin phase 1b dose escalating to determine MTD

Drug: Camsirubicin

Interventions

Camsirubicin DRUG

The dose escalation of camsirubicin will start at 265 mg/m2, with dose increments of 50% until a Grade 2 non-hematologic toxicity is observed at which point subsequent dose escalations will be in increments of 25% until an MTD is identified in patients with ASTS.

Camsirubicin + pegfilgrastim

Eligibility Criteria

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

You may qualify if:

• The participant must provide written informed consent prior to performance of study-specific procedures and must be willing to comply with treatment and follow-up. Informed consent must be obtained prior to start of the screening process. Procedures conducted as part of the patient's routine clinical management (e.g., blood count, imaging tests) and obtained prior to signature of informed consent may be used for screening or baseline purposes as long as these procedures are conducted as specified in the protocol.
• Age ≥18 years.
• Only locally confirmed histological diagnosis of advanced unresectable or metastatic malignant soft tissue sarcoma (including leiomyosarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, high-grade sarcoma \[not otherwise specified\], or synovial sarcoma) not amenable to curative treatment with surgery or radiotherapy.
• Presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• The participant has not received any previous treatment with anthracyclines (not even in adjuvant therapy).
• The participant has not had any prior systemic cytotoxic therapies for advanced/metastatic sarcoma and is considered an appropriate candidate for anthracycline therapy. All previous anticancer treatments must be completed ≥28 days prior to first dose of study drug.
• Laboratory tests must be as follows and may be repeated once at the discretion of the investigator:
• Absolute neutrophil count (ANC) ≥1,500/mm³
• Platelet count ≥100,000/mm³
• Hemoglobin \>9 g/dL
• Bilirubin \<1.5 times upper limit of normal (ULN); except subjects with Gilbert Syndrome who must have a total bilirubin level \<3.0 x ULN
• Prothrombin time (PT) (seconds) or international normalized ratio (INR) ≤1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN or, in patients with documented hepatic metastasis, ≤5 x ULN
• Serum creatinine ≤1.5 mg/dL or estimated creatinine clearance ≥60 mL/min (Cockroft and Gault)

You may not qualify if:

• Current evidence/diagnosis of alveolar soft part sarcoma, extraskeletal myxoid chondrosarcoma, rhabdomyosarcoma, osteosarcoma, gastrointestinal stromal tumor (GIST), dermatofibrosarcoma (unless transformed to fibrosarcoma), Ewing's sarcoma, Kaposi's sarcoma, mixed mesodermal tumor, or clear cell sarcomas.
• Patients who cannot tolerate pegfilgrastim.
• Known active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment. Participants with a history of a CNS metastasis previously treated with curative intent (e.g., stereotactic radiation or surgery) that have not progressed on follow-up imaging, have been asymptomatic for at least 60 days prior to first dose, and are not receiving systemic corticosteroids and or/anticonvulsants are eligible. Participants with signs or symptoms of neurological compromise should have appropriate radiographic imaging performed before enrollment to rule out brain metastasis.
• Prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones (including adjuvant therapy).
• Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation. Other thoracic radiotherapy is permitted.
• The participant has symptomatic congestive heart failure (CHF), left ventricular ejection fraction dysfunction (LVEF \<50%), severe myocardial insufficiency, cardiac arrhythmia (uncontrolled, clinically significant), or cardiomyopathy.
• The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction within 6 months of enrollment.
• The participant has a QT interval calculated using Fridericia's correction (QTcF) of \>450 milliseconds (msec) for males and \>470 msec for females on screening electrocardiogram (ECG).
• Females who are pregnant or breastfeeding.
• Known allergy to any of the treatment components including a history of allergic reactions attributed to compounds of chemical or biological composition similar to doxorubicin and camsirubicin, including intravenous (IV) lactose, or pegfilgrastim.
• The participant has a known, uncontrolled active fungal, uncontrolled bacterial, or uncontrolled viral infection including human immunodeficiency virus (HIV) or viral hepatitis (B or C).
• Any malignancy other than soft tissue sarcoma within the last 5 years prior to screening, with the exception of:
• Cervical carcinoma in situ or
• Basal cell carcinoma or
• Superficial bladder tumors that have been successfully and curatively treated with no evidence of recurrent or residual disease.

Sponsors & Collaborators

• Monopar Therapeutics: lead

Study Sites (2)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

University of Washington Medicine Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Sarcoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Holli Carlson

  Monopar Therapeutics Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2021
• First Posted: September 14, 2021
• Study Start: September 22, 2021
• Primary Completion: October 31, 2023
• Study Completion: May 13, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)