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

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

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

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: PR104
* Other: F-18-fluoromisonidazole


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PR104<br>PR104 will be administered once every 21 days by IV | Drug: PR104<br>* administered at a dose of 1100 mg/m^2 by intravenous infusion over 1 hour and repeated every three weeks<br>* Other names: PR-104;Other: F-18-fluoromisonidazole<br>* administered intravenously prior to PET scan<br>* Other names: FMISO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate (Complete or Partial) |  | From registration until disease progression/recurrence | 
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival |  | Every 3 months for 2 years after discontinuation | 
| 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 | 
| 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 | 
| Pharmacokinetics |  | Days 1 and 2 of Cycles 1 and 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extensive stage small cell lung cancer, limited stage small cell lung cancer, recurrent small cell lung cancer