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

This study has been terminated.
(Terminated early due to discovery of new mechanism of activation.)
Sponsor:
Information provided by (Responsible Party):
Proacta, Incorporated
ClinicalTrials.gov Identifier:
NCT00544674
First received: October 13, 2007
Last updated: December 6, 2012
Last verified: December 2012
  Purpose

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).


Condition Intervention Phase
Lung Cancer
Drug: PR104
Other: F-18-fluoromisonidazole
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multi-Center, Open-Label, Trial of PR104 in Treatment Naive and Sensitive-relapse Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Proacta, Incorporated:

Primary Outcome Measures:
  • Response Rate (Complete or Partial) [ Time Frame: From registration until disease progression/recurrence ] [ Designated as safety issue: No ]
  • Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events [ Time Frame: 30 days following the last administration of study treatment ] [ Designated as safety issue: Yes ]
    The number of participants with at least one Serious Adverse Event was measured.


Secondary Outcome Measures:
  • Survival [ Time Frame: Every 3 months for 2 years after discontinuation ] [ Designated as safety issue: No ]
  • Progression-free Survival [ 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 ] [ Designated as safety issue: No ]
    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 [ Time Frame: From registration of the first subject until radiological progression or recurrence whichever came first ] [ Designated as safety issue: No ]
    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 [ Time Frame: Days 1 and 2 of Cycles 1 and 4 ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: August 2007
Study Completion Date: January 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PR104
PR104 will be administered once every 21 days by IV
Drug: PR104
administered at a dose of 1100 mg/m^2 by intravenous infusion over 1 hour and repeated every three weeks
Other Name: PR-104
Other: F-18-fluoromisonidazole
administered intravenously prior to PET scan
Other Name: FMISO

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00544674

Locations
United States, Arizona
Arizona Clinical Research Center, Incorporated
Tucson, Arizona, United States, 85715
United States, California
Tower Cancer Research Foundation
Beverly Hills, California, United States, 90211
California Cancer Care, Incorporated - Greenbrae
Greenbrae, California, United States, 94904-2007
Pacific Shores Medical Group - Long Beach
Long Beach, California, United States, 90813
Stanford Cancer Center
Stanford, California, United States, 94305-5824
United States, Colorado
Front Range Cancer Specialists
Fort Collins, Colorado, United States, 80524-4038
United States, Florida
University of Florida Health Science Center - Jacksonville
Jacksonville, Florida, United States, 32209
United States, Illinois
Joliet Oncology-Hematology Associates, Limited - West
Joliet, Illinois, United States, 60435
United States, Indiana
Welborn Clinic
Evansville, Indiana, United States, 47713
United States, Kentucky
James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, United States, 40202
Kentuckiana Cancer Institute, PLLC
Louisville, Kentucky, United States, 40202
Purchase Cancer Group - Paducah
Paducah, Kentucky, United States, 42001
United States, Michigan
Barbara Ann Karmanos Cancer Institute
Detroit, Michigan, United States, 48201-1379
United States, Nevada
Cancer and Blood Specialists of Nevada - Henderson
Henderson, Nevada, United States, 89074
United States, Ohio
Gabrail Cancer Center - Canton Office
Canton, Ohio, United States, 44718
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45219
Good Samaritan Hospital Cancer Treatment Center
Cincinnati, Ohio, United States, 45220
United States, Virginia
Peninsula Cancer Institute - Newport News Office
Newport News, Virginia, United States, 23601
Sponsors and Collaborators
Proacta, Incorporated
  More Information

No publications provided

Responsible Party: Proacta, Incorporated
ClinicalTrials.gov Identifier: NCT00544674     History of Changes
Other Study ID Numbers: PR104-2001, PROACTA-PR-104-2001
Study First Received: October 13, 2007
Results First Received: June 13, 2011
Last Updated: December 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Proacta, Incorporated:
extensive stage small cell lung cancer
limited stage small cell lung cancer
recurrent small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Fluoromisonidazole
Misonidazole
Radiation-Sensitizing Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 31, 2014