PR104 in Treating Patients With Previously Untreated or Relapsed Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

A Phase II, Multi-Center, Open-Label, Trial of PR104 in Treatment Naive and Sensitive-relapse Small Cell Lung Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00544674
• Other study ID #: PR104-2001
• Secondary ID: PROACTA-PR-104-2
• Status: Terminated
• Phase: Phase 2
• First received: October 13, 2007
• Last updated: December 6, 2012
• Start date: August 2007
• Est. completion date: January 2009

Study information

• Verified date: December 2012
• Source: Proacta, Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as PR-104, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase II trial is studying how well PR-104 works in treating patients with previously untreated or relapsed small cell lung cancer (SCLC).

Description:

OBJECTIVES:

Primary

• Estimate the response rate of PR-104 in patients with treatment-naive or sensitive-relapse small cell lung cancer.

• Evaluate safety of this drug in these patients. Secondary

• Evaluate survival of these patients.

• Evaluate progression-free survival of these patients.

• Evaluate time to progression in these patients.

• Assess the pharmacokinetics (PK) of PR-104 and its alcohol metabolite.

• Estimate the rate of hypoxia using 18F-fluoromisonidazole (FMISO) positron emission topography (PET) imaging.

• Collect plasma samples for assessment of potential biomarkers of tumor hypoxia.

OUTLINE: This is a multicenter study. Patients are stratified according to disease type (treatment-naive vs sensitive-relapse).

Patients receive PR-104 intravenously (IV) over 1 hour on day 1. Treatment repeats every 21 days for up to 4 courses (for treatment-naive patients) or in the absence of disease progression or unacceptable toxicity (for sensitive-relapse patients).

PK studies are performed during course 1 and after course 3. Blood is collected at baseline, during course 1, and at study completion for biomarker studies of tumor hypoxia (plasma proteins). Patients also undergo FMISO PET and fludeoxyglucose F18 (FDG) PET scans at baseline and after the second course of study therapy.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: January 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

Inclusion criteria:

• Histologically or cytologically confirmed small cell lung cancer (SCLC)

• If patient is treatment-naive, then they must have extensive disease

• If patients are not treatment-naive, then they must be classified as sensitive-relapse with either extensive disease or limited disease

• Sensitive-relapse defined as disease that responded to first-line chemotherapy and relapsed more than 90 days following the last dose of first-line chemotherapy

• Limited disease SCLC defined as disease confined to the hemithorax of origin, mediastinum, and/or ipsilateral supraclavicular lymph nodes, which could be encompassed within a tolerable radiotherapy port

• Extensive disease defined as disease that does not fit the definition of limited disease as defined above

• Measurable or evaluable disease

Exclusion criteria:

• Active central nervous system (CNS) metastases, defined as metastases to the CNS (symptomatic or non-symptomatic) that requires immediate treatment or that are likely to require treatment in the following 6 weeks

• Medical conditions requiring urgent intervention, including any of the following:

• Superior vena cava syndrome

• Lobar obstruction

• Spinal cord compression

• Liver metastases involving greater than one-third of the liver

PATIENT CHARACTERISTICS:

Inclusion criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Hemoglobin = 9 g/dL (no red blood cell transfusions allowed)

• Serum bilirubin = 1.5 x upper limit of normal (ULN)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 x ULN (if liver metastases are present) or = 2 x ULN (if liver metastases are absent)

• Serum creatinine = 1.5 x ULN

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 30 days after completion of study treatment

Exclusion criteria:

• Prior or concurrent malignancies, except for adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or localized low-grade prostate cancer

• Hyponatremia (< 130 mmol/L)

• Evidence of a significant medical disorder or laboratory finding that, in the opinion of the investigator, compromises the patient's safety during study participation, including any of the following:

• Uncontrolled infection or infection requiring a concurrent parenteral antibiotic

• Uncontrolled diabetes

• Congestive heart failure

• Myocardial infarction within the past 6 months

• Chronic renal disease

• Coagulopathy (excluding prophylactic anticoagulation)

• Known human immunodeficiency virus (HIV) positivity, hepatitis B surface antigen-positivity, or hepatitis C positivity with abnormal liver function tests

PRIOR CONCURRENT THERAPY:

Inclusion criteria:

• See Disease Characteristics

• No concurrent prophylactic growth factors (filgrastim [G-CSF] or sargramostim [GM-CSF]) during course 1 of study treatment

Exclusion criteria:

• More than one prior chemotherapy regimen for SCLC

• Less than 24 hours from any prior radiotherapy or the likelihood of toxicity from prior radiotherapy

• Radiotherapy to > 25% of the bone marrow within the past 4 weeks

• Less than four weeks since major surgery

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• PR104
administered at a dose of 1100 mg/m^2 by intravenous infusion over 1 hour and repeated every three weeks

Other:
• F-18-fluoromisonidazole
administered intravenously prior to PET scan

Locations

Country	Name	City	State
United States	Tower Cancer Research Foundation	Beverly Hills	California
United States	Gabrail Cancer Center - Canton Office	Canton	Ohio
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital Cancer Treatment Center	Cincinnati	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Welborn Clinic	Evansville	Indiana
United States	Front Range Cancer Specialists	Fort Collins	Colorado
United States	California Cancer Care, Incorporated - Greenbrae	Greenbrae	California
United States	Cancer and Blood Specialists of Nevada - Henderson	Henderson	Nevada
United States	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Pacific Shores Medical Group - Long Beach	Long Beach	California
United States	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky
United States	Peninsula Cancer Institute - Newport News Office	Newport News	Virginia
United States	Purchase Cancer Group - Paducah	Paducah	Kentucky
United States	Stanford Cancer Center	Stanford	California
United States	Arizona Clinical Research Center, Incorporated	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Proacta, Incorporated

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response Rate (Complete or Partial)		From registration until disease progression/recurrence	No
Primary	Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events	The number of participants with at least one Serious Adverse Event was measured.	30 days following the last administration of study treatment	Yes
Secondary	Survival		Every 3 months for 2 years after discontinuation	No
Secondary	Progression-free Survival	Progression free survival (PFS) is the time (days) from date of registration to date of first observed disease progression (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before progression was documented.	Tumor measurements and assessments based on Response Evaluation Criteria In Solid Tumors (RECIST) criteria were performed 6 weeks after first dose and as dictated by subject's malignancy	No
Secondary	Time to Progression	Time to progression (TTP) was defined as the time from date of registration to radiological progression / recurrence. Subjects without progression at the time of analysis were censored at their last date of tumor evaluation.	From registration of the first subject until radiological progression or recurrence whichever came first	No
Secondary	Pharmacokinetics		Days 1 and 2 of Cycles 1 and 4	No