Clinical trial NCT00544674: PR104 in Treating Patients With Previously Untreated or Relapsed Small Cell Lung Cancer
Official title: A Phase II, Multi-Center, Open-Label, Trial of PR104 in Treatment Naive and Sensitive-relapse Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: extensive stage small cell lung cancer
limited stage small cell lung cancer
recurrent small cell lung cancer
Lead sponsor: Proacta, Incorporated
Sponsor class: INDUSTRY
First posted: 2007-10-16
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Response Rate (Complete or Partial)
timeFrame: From registration until disease progression/recurrence
measure: Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events
timeFrame: 30 days following the last administration of study treatment
Secondary outcomes:
measure: Survival
timeFrame: Every 3 months for 2 years after discontinuation
measure: Progression-free Survival
timeFrame: 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
measure: Time to Progression
timeFrame: From registration of the first subject until radiological progression or recurrence whichever came first
measure: Pharmacokinetics
timeFrame: Days 1 and 2 of Cycles 1 and 4
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Clinical Research Center, Incorporated
state: Arizona
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Greenbrae
country: United States
facility: California Cancer Care, Incorporated - Greenbrae
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group - Long Beach
state: California
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Fort Collins
country: United States
facility: Front Range Cancer Specialists
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: Joliet
country: United States
facility: Joliet Oncology-Hematology Associates, Limited - West
state: Illinois
city: Evansville
country: United States
facility: Welborn Clinic
state: Indiana
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Louisville
country: United States
facility: Kentuckiana Cancer Institute, PLLC
state: Kentucky
city: Paducah
country: United States
facility: Purchase Cancer Group - Paducah
state: Kentucky
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Henderson
country: United States
facility: Cancer and Blood Specialists of Nevada - Henderson
state: Nevada
city: Canton
country: United States
facility: Gabrail Cancer Center - Canton Office
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Good Samaritan Hospital Cancer Treatment Center
state: Ohio
city: Newport News
country: United States
facility: Peninsula Cancer Institute - Newport News Office
state: Virginia
Study officials:
References: