Efficacy and Safety Study of GPX-150 to Treat Soft Tissue Sarcoma

Soft Tissue Sarcoma Clinical Trial

Official title:

Phase 2 Efficacy and Safety Study of Intravenous GPX-150, an Anthracycline Analog, in Patients With Soft Tissue Sarcoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02267083
• Other study ID #: GPX-150-002
• Status: Completed
• Phase: Phase 2
• First received: September 23, 2014
• Last updated: December 12, 2017
• Start date: January 7, 2015
• Est. completion date: August 18, 2016

Study information

• Verified date: December 2017
• Source: Gem Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will assess the safety and efficacy of GPX-150 administered intravenously every 3 weeks in the treatment of patients with soft tissue sarcoma.

Description:

This is an open-label, single arm study of GPX-150 in patients with soft tissue sarcoma. Approximately 22 patients will be treated in this study. The population for this study is adult patients with histologically proven advanced and/or metastatic malignant soft tissue sarcoma of intermediate or high histologic grade.

All patients who meet all entry criteria will receive GPX-150 at a starting dose of 265 mg/m2 every 21 days for 16 cycles or until death, disease progression, or unacceptable toxicity or subject withdrawal.

Prior to initiation of treatment, subjects will undergo screening and baseline evaluations. During all study visits, subjects will be evaluated for safety. The dose of GPX-150 may be reduced when subjects meet specified dose reduction safety criteria. Subjects will be evaluated regularly for safety and tolerability. Tumor measurements will be calculated at baseline (within 28 days prior to treatment initiation), then at regular intervals while receiving treatment for up to 1 year. After discontinuing the treatment phase of the study, safety assessments and tumor measurements will be performed 3 weeks after the last dose of study drug.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 22
• Est. completion date: August 18, 2016
• Est. primary completion date: November 11, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years.

2. Histological documentation of soft tissue sarcoma (biopsy may be historical and may have been obtained from primary tumor or a metastatic site).

3. Advanced and/or metastatic malignant soft tissue sarcoma of intermediate or high histologic grade. Excluded are the following sarcoma subtypes:

• Well-differentiated liposarcoma or atypical lipomatous tumor

• Embryonal or alveolar rhabdomyosarcoma

• Ewing sarcoma of soft tissue or bone

• Gastrointestinal stromal tumor (GIST)

• Dermatofibrosarcoma protuberans

• Alveolar soft part sarcoma

• Solitary fibrous tumor

• Clear cell sarcoma

• Kaposi sarcoma

• Extraskeletal myxoid chondrosarcoma

• PEComa (perivascular epithelial cell tumor)

• Myoepithelioma / mixed tumor

4. Measurable disease as per RECIST 1.1.

5. Subject has received either:

• No prior chemotherapy for current sarcoma, or

• A single course of gemcitabine and/or docetaxel as adjuvant therapy that was completed at least 6 months prior to planned first dose

6. ECOG Performance Status of 0 - 2.

7. Adequate cardiac function:

• LVEF above the institution's lower limit of normal

• QTcF = 450 msec for males or 470 msec for females.

8. Willing and able to provide written informed consent.

9. Male and female subjects must agree to use a highly reliable method of birth control for the duration of the study.

10. Women of childbearing potential must have a serum pregnancy test performed within 28 days prior to the first day of study drug dosing.

Exclusion Criteria:

1. Sarcomas arising from bone or cartilage, e.g. chondrosarcoma, osteosarcoma, chordoma.

2. Subject is eligible for a potentially curative therapy.

3. Prior primary chemotherapy.

4. Prior radiotherapy to > 25% of bone marrow volume.

5. Treatment within 28 days prior to Dose 1 with:

• Palliative surgery or radiotherapy.

• Approved anticancer therapy including chemotherapy or immunotherapy.

• Contraindicated treatments noted in the product labelling for doxorubicin, including trastuzumab and inhibitors and inducers of CYP3A4, CYP2D6, or P-gp.

• An investigational therapy.

• Any major surgery (e.g. requiring general anesthesia).

6. Inadequate bone marrow, liver, and renal function, as assessed by the following laboratory parameters:

1. Absolute neutrophil count (ANC) < 1,500/mm3.

2. Platelet count < 100,000/mm3.

3. Total bilirubin > 1.5×ULN (upper limit of normal).

4. ALT and AST > 2.5×ULN. For patients with documented liver metastases, ALT and AST > 5×ULN.

5. Serum creatinine > 1.5 x ULN.

6. International Normalized Ratio (INR) and activated partial thromboplastin time [PTT] = 1.5×ULN, if not therapeutically anticoagulated.

7. Serum albumin < 3.0 gm/dL.

7. Congestive heart failure > Class II New York Heart Association Functional Classification, current pericarditis, myocardial infarction within 6 months, or symptomatic coronary artery disease.

8. Unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a patient and/or their compliance with the protocol.

9. Active infection requiring systemic antibacterial/antibiotic, antifungal, or antiviral therapy.

10. Documented metastases to brain or meninges.

11. Any malignancy other than soft tissue sarcoma within the last 5 years prior to screening, with the exception of cervical carcinoma in situ, basal cell carcinoma, or superficial bladder tumors that have been successfully and curatively treated with no evidence of recurrent or residual disease.

12. Body surface area (BSA) = 2.4 m2.

13. Currently pregnant or nursing.

14. Known allergy to any of the study drugs or their excipients.

Related Conditions & MeSH terms

• Sarcoma
• Soft Tissue Sarcoma

Intervention

Drug:
• GPX-150 for Injection
GPX-150 at a starting dose of 265 mg/m2 every 21 days for 16 cycles or until death, disease progression, or unacceptable toxicity. The dose of GPX-150 may be reduced by 25% if any dose reduction criteria are met. Two reductions are allowed per subject during the course of the study.

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	University of Iowa Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Gem Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Subjects With Tumor Response Per RECIST 1.1	Tumor assessments using contrast enhanced computerized tomography (CT) scan of the Chest/Abdomen/Pelvis were performed to assess overall tumor burden. Response rate (RR), where response is defined as complete response (CR), partial response (PR), or stable disease (SD). Determination of CR or PR requires confirmation at the time of the next tumor assessment. An outcome of SD requires at least one assessment 6 weeks after the initiation of dosing. Progression is defined using RECIST 1.1, as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).	Assessed during screening, then every 6 weeks for the first 24 weeks on study, and then every 9 weeks for the next 24 weeks for up to 1 year. Subjects will be in the study for up to 1 year, or until disease progression or unacceptable toxicity.
Primary	Number of Subjects Progression-free at 12 Months Per RECIST 1.1	The primary efficacy endpoint is the number of patients who were progression-free at 12 months, which is obtained by inversion of the Kaplan-Meier curve for progression-free survival (PFS) at 12 months. Of note, the statistical comparison to historical sarcoma data described in the protocol was not performed due to an enrollment of less than the planned sample size of 30 subjects. Progression is defined using RECIST 1.1, as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).	12 months from the beginning of study treatment
Secondary	Number of Subjects Progression-free at Six Months Per RECIST 1.1	This secondary efficacy endpoint is the progression-free rate (PFR) at 6 months, obtained from the Kaplan-Meier curve for progression-free survival (PFS).	6 months from the beginning of the study treatment
Secondary	Number of Subjects Experiencing Adverse Events	Subjects who received at least one dose were included in safety analyses. Adverse events were tabulated by System Organ Class (SOC) and Preferred Term (PT) and coded using MedDRA Version 19.1. Safety and tolerability was determined by frequency, nature, and severity of adverse events and the profile of toxicities.	From the beginning of study treatment and up to 12 months