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

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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Small Cell Lung Cancer
• Intervention / Treatment: Drug: Aldoxorubicin; Drug: Topotecan

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary
    • Koranyi National Institute of TBC and Pulmonologyhhy
  • Budapest, Hungary
    • Koranyi National Institute of TBC and Pulmonology
  • Debrecen, Hungary
    • University of Debrecen, Medical and Health Science Center, Department of Pulmonology
  • Nyiregyhaza, Hungary
    • Szabolcs-Szatmar-Bereg County Hospitals and University Teaching Hospital, Department of Pulmonology
  • Pecs, Hungary
    • Medical Center of the University of Pecs, 1st Department of Internal Medicine
  • Szolnok, Hungary
    • Hetenyi Geza Hospital
• Spain
  • Alicante, Spain
    • Hospital General Universitario de Alicante
  • Barcelona, Spain
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain
    • University Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Universitario Quiron-Dexeus (IOR)
  • Lugo, Spain
    • Hospital Universitario Lucus Augusti
  • Madrid, Spain
    • Hospital Puerta de Hierro
  • Madrid, Spain
    • University Hospital La Paz
  • Madrid, Spain
    • General University Hospital Gregorio Maranon
  • Madrid, Spain
    • University Hospital Foundation Jimenez Diaz
  • Malaga, Spain
    • Hospital Regional Universitario
  • Sevilla, Spain
    • University Hospital Virgen de Valme
  • Vigo, Spain
    • CHU Xeral
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Pasadena, California, United States, 91030
      • City of Hope Medical Group
  • Florida
    • Fleming Island, Florida, United States
      • Cancer Specialists of North Florida-Fleming Island
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, P.C.
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hermatology Care, Inc.
  • Oregon
    • Portland, Oregon, United States, 97227
      • Northwest CCOP Kaiser Permanente
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Cancer Institute
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Tennessee Oncology
    • Knoxville, Tennessee, United States, 37909
      • Tennessee Cancer Specialists
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Topotecan	Drug: 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; Other Names: Hycamtin
Experimental: Aldoxorubicin	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.; Other Names: INNO-206

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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. Progressive Disease is defined as: ≥20% increase in the sum of the longest diameter of target lesions from the smallest sum of the longest diameter recorded since the treatment started; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of ≥1 new lesion is also considered progression.	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-related Toxicities (Adverse Events)	Treatment was planned to continue until tumor progression is observed, subject asks to withdraw, or unacceptable toxicity occurs, up to 451 days.

Collaborators and Investigators

• Sponsor: ImmunityBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2015
• Primary Completion (Actual): May 15, 2017
• Study Completion (Actual): May 15, 2017

Study Registration Dates

• First Submitted: July 23, 2014
• First Submitted That Met QC Criteria: July 24, 2014
• First Posted (Estimated): July 25, 2014

Study Record Updates

• Last Update Posted (Actual): June 25, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Topotecan
• Other Study ID Numbers: ALDOXORUBICIN-P2-SCLC-01