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

• Sponsor: Proacta, Incorporated (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00544674
• Collaborator: (none)
• Enrollment: 5
• Locations: 18
• Arm: 1
• Duration (Months): 17.1
• Patients Per Site: 0.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Lung Cancer	Drug: PR104; Other: F-18-fluoromisonidazole	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: Aug 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jan 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
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 Names: PR-104 ; Other: F-18-fluoromisonidazole; administered intravenously prior to PET scan; Other Names: FMISO

Outcome Measures

Primary Outcome Measures

1. Response Rate (Complete or Partial) [From registration until disease progression/recurrence]

2. 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 Outcome Measures

1. Survival [Every 3 months for 2 years after discontinuation]

2. 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.

3. 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.

4. Pharmacokinetics [Days 1 and 2 of Cycles 1 and 4]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Arizona Clinical Research Center, Incorporated	Tucson	Arizona	United States	85715
2	Tower Cancer Research Foundation	Beverly Hills	California	United States	90211
3	California Cancer Care, Incorporated - Greenbrae	Greenbrae	California	United States	94904-2007
4	Pacific Shores Medical Group - Long Beach	Long Beach	California	United States	90813
5	Stanford Cancer Center	Stanford	California	United States	94305-5824
6	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80524-4038
7	University of Florida Health Science Center - Jacksonville	Jacksonville	Florida	United States	32209
8	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
9	Welborn Clinic	Evansville	Indiana	United States	47713
10	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
11	Kentuckiana Cancer Institute, PLLC	Louisville	Kentucky	United States	40202
12	Purchase Cancer Group - Paducah	Paducah	Kentucky	United States	42001
13	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan	United States	48201-1379
14	Cancer and Blood Specialists of Nevada - Henderson	Henderson	Nevada	United States	89074
15	Gabrail Cancer Center - Canton Office	Canton	Ohio	United States	44718
16	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio	United States	45219
17	Good Samaritan Hospital Cancer Treatment Center	Cincinnati	Ohio	United States	45220
18	Peninsula Cancer Institute - Newport News Office	Newport News	Virginia	United States	23601

Sponsors and Collaborators

• Proacta, Incorporated

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Proacta, Incorporated
• ClinicalTrials.gov Identifier: NCT00544674
• Other Study ID Numbers: PR104-2001; PROACTA-PR-104-2001
• First Posted: Oct 16, 2007
• Last Update Posted: Dec 10, 2012
• Last Verified: Dec 1, 2012

• 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

Study Results

Participant Flow

Arm/Group Title	PR104
Arm/Group Description	Subjects will receive 1100 mg/m^2 PR-104 intravenously once every 21 days (one cycle). In addition, subjects will undergo positron emission topography (PET) imaging with F-18-Fluoro Misonidazole (FMISO) for the assessment of hypoxia and with F-18-Fluorodeoxyglucose (FDG) for the assessment of glucose metabolism.
Period Title: Overall Study
STARTED	5
COMPLETED	4
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	PR104
Arm/Group Description	1100 mg/m^2 PR104 by IV over one hour every three weeks
Overall Participants	5
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	2 40%
>=65 years	3 60%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (9.19)
Sex: Female, Male (Count of Participants)
Female	1 20%
Male	4 80%
Region of Enrollment (participants) [Number]
United States	5 100%

Outcome Measures

1. Primary Outcome

Title	Response Rate (Complete or Partial)
Time Frame	From registration until disease progression/recurrence

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

2. Secondary Outcome

Title	Survival
Time Frame	Every 3 months for 2 years after discontinuation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Progression-free Survival
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Time to Progression
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Primary Outcome

Title	Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events
Description	The number of participants with at least one Serious Adverse Event was measured.
Time Frame	30 days following the last administration of study treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PR104
Arm/Group Description	1100 mg/m^2 PR104 by IV over one hour every three weeks
Measure Participants	4
Number [participants]	2 40%

6. Secondary Outcome

Title	Pharmacokinetics
Time Frame	Days 1 and 2 of Cycles 1 and 4

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	PR104
Arm/Group Description	1100 mg/m^2 PR104 by IV over one hour every three weeks
All Cause Mortality
	PR104
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PR104
	Affected / at Risk (%)	# Events
Total	2/4 (50%)
Gastrointestinal disorders
Vomiting	1/4 (25%)
Metabolism and nutrition disorders
Dehydration	1/4 (25%)
Other (Not Including Serious) Adverse Events
	PR104
	Affected / at Risk (%)	# Events
Total	4/4 (100%)
Blood and lymphatic system disorders
Anaemia	2/4 (50%)
Neutropenia	2/4 (50%)
Thrombocytopenia	2/4 (50%)
Leukopenia	1/4 (25%)
Pancytopenia	1/4 (25%)
Ear and labyrinth disorders
Tinnitus	1/4 (25%)
Gastrointestinal disorders
Nausea	1/4 (25%)
General disorders
Fatigue	2/4 (50%)
Chest pain	1/4 (25%)
Infections and infestations
Pneumonia	1/4 (25%)
Investigations
Weight decreased	1/4 (25%)
Nervous system disorders
Dizziness	1/4 (25%)
Dysgeusia	1/4 (25%)

Limitations/Caveats

Decision to close study early based on new data showing that PR104A could also be activated under oxic conditions in tumors that express high levels of AKR1C3. SCLC does not express meaningful levels of the enzyme aldo keto reductase 1C3 (AKR1C3).

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Single site data may be published/presented prior to the publication of multi-center data from overall study if agreed to by the sponsor in writing, or 12 months have elapsed following termination or completion of the study, whichever comes first.