Phase I Study of Weekly Topotecan in Combination With Sorafenib in Treatment of Relapsed Small Cell Lung Cancer

NCT00466232 | Completed Phase 1

• 1 other identifier: 3557-07-C
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this study is to determine the maximum tolerated dose of sorafenib up to the full active dose when combined with standard weekly dosing of topotecan in patients with recurrent small cell lung cancer and to characterize the toxicities associated with the combination of topotecan and sorafenib in this patient population

Conditions

Small Cell Carcinoma; Lung Cancer

Keywords

Small Cell; Lung Cancer; Treatment

Outcome Measures

Primary Outcomes (2)

• The primary objective of this study is to determine the maximum tolerated dose of sorafenib up to the full active dose when combined with standard weekly dosing of topotecan in patients with recurrent small cell lung cancer and to

  2 years

• characterize the toxicities associated with the combination of topotecan and sorafenib in this patient population

  2 years

Secondary Outcomes (4)

• To evaluate the objective response rate (CR, PR or stable disease)

  2 years

• To measure time-to-event efficacy looking at the following variables:

  2 years

• o Time to disease progression

  2 years

• o Overall survival

  2 years

Study Arms (1)

1

EXPERIMENTAL

Weekly Topetecan in combination with Sorafenib

Drug: Topotecan; Drug: Sorafenib

Interventions

Topotecan DRUG

4 mg/m2 IV on day 1, 8, 15. Repeat every 28 days.

Also known as: Hycamtin

1

Sorafenib DRUG

Dose escalation study at 3 dose levels: 200 mg po daily, 200 mg po bid, 400 mg po bid.

Also known as: Nexavar

1

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically proven small cell carcinoma of bronchogenic origin.
• Must have received one course of systemic chemotherapy which included cisplatin or carboplatin. Chemotherapy administered during radiation is allowable.
• Must have radiographically documented disease recurrence or progression by CT scan or bone scan. CNS only recurrence is not sufficient. Measurable disease per RECIST criteria is not required.
• ECOG Performance status of 0 to 2
• Adequate organ function within 14 days of study enrollment as defined by the following:
• Absolute neutrophil count ≥ 1500/mm3
• Platelet count ≥ 100,000/mm3
• Hemoglobin ≥ 9 gm/dL
• Creatinine ≤ 1.5 mg/dL
• Bilirubin \< 1.5 times upper limit of normal (x UNL)
• Alkaline phosphatase, aspartate transaminase and alanine transaminase \< 3 x ULN (may be \<5 x ULN if hepatic metastases)
• Women of childbearing potential and sexually active males must use an effective method of contraception during the study and for 3 months after the last dose of study drug.
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment.
• Treated brain metastases that are stable for a minimum of 4 weeks following surgery or radiation and off therapeutic glucocorticoids are allowed.
• INR\<1.5 or a PT/PTT within normal limits. Patients receiving anti- coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the INR should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable.

You may not qualify if:

• Pregnant or breast feeding.
• Myocardial infarction or cerebrovascular accident within 6 months.
• Uncontrolled hypertension defined as systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg despite optimal medical management.
• History of other active invasive malignancy (except for basal cell or squamous cell skin cancer) within 12 months.
• Major surgery within 4 weeks.
• Chemotherapy within 4 weeks.
• Cardiac disease: Congestive heart failure \> NYHA Class II, unstable or new-onset angina within prior 3 months.
• History of bleeding diathesis or coagulopathy.
• Active clinically serious infection \> CTCAE Grade 2.
• Ventricular arrhythmias requiring anti-arrhythmic therapy.
• Serious non-healing wound, ulcer or fracture.
• Any hemorrhage or bleeding event \> CTCAE Grade 3 within 4 weeks of study enrollment.
• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
• Thrombotic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months.
• Known human immunodeficiency virus (HIV) or chronic hepatitis B or C infection.

Sponsors & Collaborators

• HealthPartners Institute: lead

Study Sites (1)

Park Nicollet Institute

Saint Louis Park, Minnesota, 55416, United States

Location

MeSH Terms

Conditions

Carcinoma, Small Cell; Lung Neoplasms

Interventions

Topotecan; Sorafenib

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Joseph Leach, MD

  HealthPartners Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: April 24, 2007
• First Posted: April 27, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: March 1, 2010
• Last Updated: December 16, 2015

Record last verified: 2007-04

Locations

US (1)