Camsirubicin + Pegfilgrastim to Determine MTD in ASTS

• Status: Recruiting
• Trial end date: 2025-06-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Monopar Therapeutics

Criteria

Inclusion Criteria:

1. 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, etc.) 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.

2. Age ≥18 years.

3. Only locally confirmed histological diagnosis of advanced unresectable or metastatic soft tissue sarcoma (leiomyosarcoma, dedifferentiated liposarcoma, myxoid liposarcoma, pleomorphic liposarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor or synovial sarcoma) not amenable to curative treatment with surgery or radiotherapy.

4. Mandatory pre-treatment formalin-fixed paraffin embedded (FFPE) tumor tissue (taken within 18 months before enrollment) must be provided for all subjects without exception for local pathology review.

5. Presence of measurable disease as defined by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

6. Performance status 0-1 on the Eastern Cooperative Oncology Group (ECOG) scale.

7. The participant has not received any previous treatment with anthracyclines (not even in adjuvant therapy).

8. 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 ≥21 days prior to first dose of study drug.

9. Adequate hepatic, renal, cardiac, and hematologic function prior to enrollment.

10. Laboratory tests must be as follows and may be repeated once at the discretion of the investigator:

• Absolute neutrophil count (ANC) ≥1,200/mm³

• Platelet count ≥100,000/mm³

• Hemoglobin >9 g/dL

• Total Bilirubin ≤1.5 mg/dL

• Prothrombin time (PT) [seconds] or international normalized ratio (INR) ≤1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times ULN

• Estimated creatinine clearance ≥80 mL/min (Cockcroft and Gault)

11. Left ventricular ejection fraction (LVEF) ≥50% assessed within 28 days prior to enrollment.

12. Females of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to enrollment. A female is eligible to enter and participate in the study if she is of non-childbearing potential (i.e. physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, a bilateral oophorectomy (ovariectomy), a bilateral tubal ligation or is post-menopausal with a minimum of 1 year without menses.

13. Both males and females must agree to use highly effective contraceptive precautions if conception is possible during the dosing period and up to 3 months following the last dose of study drug.

14. Female patients who are lactating must agree to discontinue nursing prior to the first dose of study drug and must refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug.

15. The participant has, in the opinion of the Investigator, a life expectancy of at least 3 months.

Exclusion Criteria:

1. Patients who cannot tolerate pegfilgrastim.

2. Known active central nervous system (CNS) or leptomeningeal metastasis (brain metastasis) at the time of enrollment.

3. Prior treatment with doxorubicin, epirubicin, idarubicin, and/or other anthracyclines or anthracenediones (including adjuvant therapy).

4. Prior radiotherapy of the mediastinal/pericardial area or whole pelvis radiation. Other thoracic radiotherapy is permitted.

5. The participant has symptomatic congestive heart failure (CHF), left ventricular dysfunction (LVEF <50%), severe myocardial insufficiency, cardiac arrhythmia (uncontrolled clinically significant), or cardiomyopathy.

6. The participant has unstable angina pectoris, angioplasty, cardiac stenting, or myocardial infarction.

7. 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).

8. Females who are pregnant or breastfeeding.

9. 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 IV lactose) or pegfilgrastim.

10. The participant has a known, uncontrolled active fungal, bacterial or viral infection including human immunodeficiency virus (HIV) or viral hepatitis (B or C).

11. History of another cancer with the exception of:

• adequately treated basal cell carcinoma or skin squamous cell carcinoma or

• adequately treated in situ cervical cancer or

• superficial bladder cancer or

• low risk prostate cancer or

• relapse-free interval longer than 3 years after treatment of a primary cancer with no substantial risk of recurrence.

12. Conditions which would confound the assessment of the effects and/or safety of study medication in the opinion of the investigator.