Lung Cancer
Conditions
Keywords
extensive stage small cell lung cancer, limited stage small cell lung cancer, recurrent small cell lung cancer
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.
Interventions
DRUGPR104
administered at a dose of 1100 mg/m\^2 by intravenous infusion over 1 hour and repeated every three weeks
administered intravenously prior to PET scan
Sponsors
Proacta, Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate (Complete or Partial) | From registration until disease progression/recurrence | — |
| Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events | 30 days following the last administration of study treatment | The number of participants with at least one Serious Adverse Event was measured. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival | Every 3 months for 2 years after discontinuation | — |
| Progression-free Survival | 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 | 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. |
| Time to Progression | From registration of the first subject until radiological progression or recurrence whichever came first | 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. |
| Pharmacokinetics | Days 1 and 2 of Cycles 1 and 4 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PR104 1100 mg/m\^2 PR104 by IV over one hour every three weeks | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | PR104 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age Continuous | 63 years STANDARD_DEVIATION 9.19 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 4 |
| serious Total, serious adverse events | 2 / 4 |
Outcome results
Primary
Response Rate (Complete or Partial)
Time frame: From registration until disease progression/recurrence
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.
Time frame: 30 days following the last administration of study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PR104 | Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events | 2 participants |
Secondary
Pharmacokinetics
Time frame: Days 1 and 2 of Cycles 1 and 4
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.
Time frame: 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
Secondary
Survival
Time frame: Every 3 months for 2 years after discontinuation
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.
Time frame: From registration of the first subject until radiological progression or recurrence whichever came first