Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer

Metastatic Small Cell Lung Cancer Clinical Trial

Official title:

A Multicenter, Randomized, Open-Label Phase 2b Study to Investigate the Efficacy and Safety of Aldoxorubicin Compared to Topotecan in Subjects With Metastatic Small Cell Lung Cancer Who Either Relapsed or Were Refractory to Prior Chemotherapy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02200757
• Other study ID #: ALDOXORUBICIN-P2-SCLC-01
• Status: Recruiting
• Phase: Phase 2
• First received: July 23, 2014
• Last updated: August 17, 2016
• Start date: September 2014
• Est. completion date: July 2017

Study information

• Verified date: January 2016
• Source: CytRx
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of aldoxorubicin compared to topotecan in subjects with metastatic small cell lung cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 132
• Est. completion date: July 2017
• Est. primary completion date: September 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age =18 years male or female.

2. Histological confirmation of SCLC.

3. Relapsed or refractory to no more than 1 course of a systemic therapy regimen and is incurable by either surgery or radiation.

4. Capable of providing informed consent and complying with trial procedures.

5. ECOG PS 0-2.

6. Life expectancy >8 weeks.

7. Measurable tumor lesions according to RECIST 1.1 criteria.[22]

8. Women must not be able to become pregnant (e.g. post-menopausal for at least 1 year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. (Adequate contraception includes: oral contraception, implanted contraception, intrauterine device implanted for at least 3 months, or barrier method in conjunction with spermicide.)

9. Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (see Inclusion 8 plus condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and for 6 months after the final dose of study treatment.

10. Women of child bearing potential must have a negative serum or urine pregnancy test at the Screening Visit and be non-lactating.

11. Accessibility to the site that ensures the subject will be able to keep all study-related appointments.

Exclusion Criteria:

1. Prior exposure to >375 mg/m2 of doxorubicin or liposomal doxorubicin.

2. Prior treatment with topotecan.

3. Palliative surgery and/or radiation treatment < 21 days prior to date of randomization.

4. Exposure to any investigational agent within 30 days of date of randomization.

5. Exposure to any systemic chemotherapy within 21 days of date of randomization.

6. Active (symptomatic) central nervous system (CNS) metastasis.

7. History of other malignancies except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix unless documented free of cancer for =3 years.

8. Laboratory values: Screening serum creatinine >1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) >3×ULN or >5×ULN if liver metastases are present, total bilirubin >2×ULN, absolute neutrophil count (ANC) <1,500/mm3, platelet concentration <100,000/mm3, hemoglobin <9 g/dL, albumin <2 gm/dL.

9. Anion gap > 16 meq/L or arterial blood pH < 7.30.

10. Clinically evident congestive heart failure (CHF) > class II of the New York Heart Association (NYHA) guidelines (Appendix D).

11. Current, serious, clinically significant cardiac arrhythmias, defined as the existence of an absolute arrhythmia or ventricular arrhythmias classified as Lown III, IV or V (Appendix F).

12. Baseline QTc >470 msec measured by Fridericia's formula (QTcF) and/or previous history of QT prolongation while taking other medications. Concomitant use of medications associated with a high incidence of QT prolongation is not allowed.

13. History or signs of active coronary artery disease with angina pectoris within the last 6 months.

14. Serious myocardial dysfunction defined by ECHO as absolute left ventricular ejection fraction (LVEF) below the institution's lower limit of predicted normal.

15. Known history of HIV infection.

16. Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals.

17. Treatment with p-glycoprotein inhibitors such as cyclosporine A, elacridar, ketoconazole, ritonavir, saquinavir.

18. Major surgery within 30 days prior to date of randomization.

19. Substance abuse or any condition that might interfere with the subject's participation in the study or in the evaluation of the study results.

20. Any condition that is unstable and could jeopardize the subject's participation in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Neoplasms
• Metastatic Small Cell Lung Cancer
• Small Cell Lung Carcinoma

Intervention

Drug:
• Aldoxorubicin
230 mg/m2 (170 mg/m2 doxorubicin equivalent) intravenously on Day 1 of each 21-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs.
• Topotecan
1.5 mg/m2/day intravenously for 5 consecutive days on Day 1 of each 21-day cycle OR 4 mg/m2 intravenously on Days 1, 8 and 15 of each 28-day cycle. Number of cycles: until tumor progression or unacceptable toxicity occurs

Locations

Country	Name	City	State
Hungary	Koranyi National Institute of TBC and Pulmonology	Budapest
Hungary	Koranyi National Institute of TBC and Pulmonologyhhy	Budapest
Hungary	University of Debrecen, Medical and Health Science Center, Department of Pulmonology	Debrecen
Hungary	Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Pulmonology	Nyiregyhaza
Hungary	Medical Center of the University of Pecs, 1st Department of Internal Medicine	Pecs
Hungary	Hetenyi Geza Hospital	Szolnok, Jasz-Nagykun-Szolnok
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitario Quiron-Dexeus (IOR)	Barcelona
Spain	University Hospital Vall d'Hebron	Barcelona
Spain	Hospital Universitario Lucus Augusti	Lugo
Spain	General University Hospital Gregorio Maranon	Madrid
Spain	Hospital Puerta de Hierro	Madrid
Spain	University Hospital Foundation Jimenez Diaz	Madrid
Spain	University Hospital La Paz	Madrid
Spain	Hospital Regional Universitario	Malaga
Spain	University Hospital Virgen de Valme	Sevilla
Spain	CHU Xeral	Vigo
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	Lynn Cancer Institute	Boca Raton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Tennessee Oncology	Cattanooga	Tennessee
United States	Oncology Hermatology Care, Inc.	Cincinnati	Ohio
United States	Bay Hematology Oncology	Easton	Maryland
United States	Cancer Specialists of North Florida-Fleming Island	Fleming Island	Florida
United States	Penn State Hershey Cancer Institute	Hershey	Pennsylvania
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	Cedars-Sinai Medical Center	Los Angeles	California
United States	James Graham Brown Cancer Center	Louisville	Kentucky
United States	Northwest Georgia Oncology Centers, P.C.	Marietta	Georgia
United States	West Jefferson Medical Center, Cancer Center	Marrero	Louisiana
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	City of Hope Medical Group	Pasadena	California
United States	Hematoloy Oncology Associates	Port St. Lucie	Florida
United States	Northwest CCOP Kaiser Permanente	Portland	Oregon
United States	Washington University School of Medicine, Department of Internal Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
CytRx

Countries where clinical trial is conducted

United States,  Hungary,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-Free Survival (PFS)	PFS is defined as the time from the date of randomization to first documentation of objective tumor progression or to death due to any cause in the absence of previous documentation of objective tumor progression.	24 months	No
Secondary	Overall Survival (OS)	Overall survival is defined as the time from randomization to date of death. In the absence of confirmation of death, survival time will be censored at the last date the subject is known to be alive.	36 months	No
Secondary	Safety Measures	The safety of aldoxorubicin compared to topotecan in this population assessed by the frequency and severity of adverse events (AEs), abnormal findings on physical examination, laboratory tests, vital signs, echocardiogram (ECHO) evaluations, electrocardiogram (ECG) results, and weight, as well as disease control rate and tumor response.	24 months	Yes