Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Lenograstim

Tubulin Modulators

Antimitotic Agents

Adjuvants, Immunologic

Immunologic Factors

Subjects randomized to the docetaxel arm will be administered 75 mg/m\^2, IV, every 21 days (an approved dose and schedule)

Subjects randomized to the PR104/docetaxel arm will be administered 60 mg/m\^2 docetaxel, IV, every 21 days plus 770 mg/m\^2 PR104, IV, every 21 days and prophylactic G-CSF.

770 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

PR104

75 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

docetaxel

60 mg/m\^2, IV, every 21 days. Number of Cycles: until progression or unacceptable toxicity develops.

Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF per package insert administration recommendations. Number of Cycles: until progression or unacceptable toxicity develops.

Granulocyte colony-stimulating factor

The current understanding of PR104 justifies the evaluation of PR104 with docetaxel in subjects with Non Small Cell Lung Cancer (NSCLC). These include:

* Aldo-keto reductase 1C3 (AKR1C3). NSCLC has been shown to express high levels of AKR1C3 in about one half of tumors tested. Subjects with high levels of AKR1C3 should have increased activation of PR104 within their tumor.
* Hypoxia. NSCLC has been demonstrated to be a tumor with hypoxia based on both direct tumor measurements (oxygen electrodes) and hypoxic positron emission tomography (PET) imaging. Tumor hypoxia in NSCLC should be sufficient to activate PR104 to its active metabolites PR104H and PR104M.
* Preclinical data. The use of docetaxel and PR104 alone and in combination in preclinical models demonstrates activity of PR104 as a single agent and supraadditive activity when PR104 and docetaxel are used in combination.
* Manageable toxicity. PR104 and docetaxel with Granulocyte Colony-stimulating Factor (G-CSF) have been combined in a prior phase I study. A Maximum Tolerated Dose (MTD) has been identified and the major toxicities of this combination are understood.

The current study will provide an estimate of the activity of PR104 in subjects with NSCLC. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity in NSCLC to warrant a larger phase III registration study in this indication.

Primary objectives

• Estimate the response rate (RR) of PR104/docetaxel

Secondary objectives

* Evaluate survival
* Evaluate progression free survival (PFS)
* Evaluate time to progression (TTP)
* Evaluate safety
* Evaluate the pharmacokinetics of PR104 and its metabolites
* Evaluate the pharmacokinetics of docetaxel
* Evaluate the tumor hypoxia using 18F-fluoromisonidazole (18F-MISO) PET imaging
* Collect diagnostic biopsy samples for the determination of AKR1C3
* Collect plasma samples for assessment of potential biomarkers of tumor hypoxia

A randomized phase II, multi-center, open-label, study of docetaxel versus docetaxel/PR104.

Following informed consent, subjects will undergo baseline evaluation with history, physical exams, blood work and disease assessment. Selected subjects will undergo PET imaging with F18 fluoromisonidazole (F18-FMISO) and Fludeoxyglucose (FDG) for assessment of hypoxia and glucose metabolism, and pharmacokinetics of PR104.

Subjects will be randomized between arm 1 consisting of docetaxel, 75 mg/m\^2, administered intravenously (IV), every 21 days (an approved dose and schedule) and arm 2 consisting of docetaxel, 60 mg/m\^2 with PR104 at 770 mg/m\^2, IV, every 21 days. Subjects randomized to PR104/docetaxel will receive prophylactic G-CSF. One cycle will be 21 days in duration. Subjects will be evaluated weekly. A disease assessment will be performed every six weeks. Subjects with progression will be removed from study. Subjects with a response or stable disease may continue on study if this is considered beneficial by their physician.

Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)

A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer

Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria

The number of participants with at least one Serious Adverse Event was measured.

AKR1C3 was evaluated on a semi-quantitative scale, and the percentage of cells staining at each of the following four levels was recorded: 0 (unstained), 1+ (weak staining), 2+ (moderate staining) and 3+ (strong staining).

Patients with a strong staining score (3+) were considered to be AKR1C3 positive

Proacta, Incorporated

PR104 + Docetaxel

Total

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Canada

Region of Enrollment

Director of Clinical Development

Complete Response (CR)

Partial Response (PR)

Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone

Safety and Tolerability: Serious Adverse Events

Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients

Subjects randomized to the PR104/docetaxel arm will be administered 60 mg/m\^2 docetaxel, IV, every 21 days plus 770 mg/m\^2 PR104, IV, every 21 days and prophylactic Granulocyte Colony-stimulating Factor (G-CSF).

Overall Study

filgrastim will be administered at a standard dose and schedule

filgrastim

PR104 is administered intravenously once every 21 days

F-18-fluoromisonidazole is administered intravenously prior to performance of PET scan

F-18-fluoromisonidazole

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. Colony-stimulating factors, such as G-CSF, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy. Giving PR-104 together with G-CSF may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of PR-104 when given together with G-CSF in treating patients with solid tumors.

OBJECTIVES:

Primary

* Determine the maximum tolerated dose of PR-104 in combination with filgrastim (G-CSF) in patients with solid tumors.

Secondary

* Characterize the safety of this regimen in these patients.
* Evaluate the pharmacokinetics of PR-104 and its alcohol metabolite.
* Evaluate the rate of hypoxia in various solid tumors using F-MISO PET (18F-fluoromisonidazole positron emission tomography) imaging.
* Assess for antitumor toxicity in these patients.
* Collect plasma samples for the assessment of potential biomarkers of tumor hypoxia.

OUTLINE: This is a multicenter, dose-escalation study of PR-104.

Patients receive PR-104 IV over 1 hour on day 1 and filgrastim (G-CSF) on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo 18F-fluoromisonidazole PET scans at baseline and prior to course 3 to assess tumor hypoxia.

Patients undergo blood sample collection periodically during course 1. Samples are analyzed for the pharmacokinetics of PR-104 and for identification of biomarkers for tumor hypoxia.

After completion of study treatment, patients are followed at 30 days.

PR104 and G-CSF in Treating Patients With Solid Tumors

A Phase I, Multi-Center, Open-Label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR104 Given With Prophylactic G-CSF in Subjects With Solid Tumors

Brenda Gibson, Assoc. Director

Symptoms and General Pathology

Immune System Diseases

Rare Diseases

Recurrence

Hypersensitivity

Small Cell Lung Carcinoma

Small Cell Lung Cancer

PR104 will be administered once every 21 days by IV

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

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).

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.

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

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

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 (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.

1100 mg/m\^2 PR104 by IV over one hour every three weeks

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).

Response Rate (Complete or Partial)

Survival

Progression-free Survival

Time to Progression

Safety and Tolerability: the Number of Subjects Experiencing a Serious Adverse Events

Pharmacokinetics

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.

Dose escalation of PR104 to determine maximum tolerated dose for weekly administration

Mark McKeage, PhD, FRACP

The purpose of this study is to determine the side effects and best weekly dose of PR104 in patients with advanced solid tumors.

A Phase I Dose Escalation Trial of PR104 Given Weekly in Subjects With Solid Tumors

A Phase I, Multi-center, Open-label, Dose Escalation Trial of the Safety and Pharmacokinetics of Intravenous PR104 Given Weekly in Subjects With Solid Tumors

MTD is based on cycle 1 data and defined as the maximum dose that can be administered to 6 subjects with no more than one of the following DLTs:

* Grade 4 thrombocytopenia
* Grade 4 heme toxicity (excluding thrombocytopenia) that lasts for ≥ 5 days (Neutrophils \< 500/mm3, ANC ≤ 0.5 K/mm3, lymphocytes \< 1K/mm3, HGB \< 6.5 gm/dL)
* Non-heme toxicity ≥ Grade 3 despite appropriate treatment
* Neutropenic fever
* Grade 2 or higher neurotoxicity of ≥ 1 week
* Any toxicity of Grade 2 or higher that has not resolved within 2 weeks of end of cycle 1 (except grade 2 alopecia)

Blood and Lymph Conditions

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Lymphosarcoma

Nine pre-defined dose levels for specific subsets of subjects will be administered by IV (in the vein). PR104 will be administered initially as induction therapy followed by administration as consolidation therapy, as is typical of established treatment regimens in AML.

The current understanding of PR104 justifies the evaluation of PR104 in subjects with relapsed/refractory AML and ALL. These include:

* Hypoxia. Leukemic bone marrow is likely to demonstrate a level of hypoxia sufficient to activate PR104 to its active metabolites PR104H and PR104M.
* Myelotoxicity as the primary toxicity at MTD. In prior clinical studies in subjects with solid tumors PR104 has demonstrated myelotoxicity as the primary toxicity. This observation suggests that PR104 will exert a similar effect on leukemic cells.
* AKR1C3. AML has been reported to exhibit high levels of AKR1C3 which should lead to selective activation of PR104 within both hypoxic and oxic leukemic cells.
* Preclinical data. PR104 has demonstrated impressive activity in an initial study using primary human ALL in a mouse model.

The initial dose finding phase of the study will provide estimates of the activity and toxicity of PR104 in subjects with refractory/relapsed AML, and determine the optimal individualized dose to give each subject based on his/her covariates (prior CR duration, prior number of salvage therapies, age). Once a potentially beneficial dose has been determined, an expanded cohort of subjects with AML or ALL will receive PR104 at a uniform dose. This information will prove valuable in defining the future clinical development of PR104, and in determining if PR104 has sufficient activity and acceptable safety in AML to warrant future phase II or phase III studies in this indication.

Primary objectives

* Determine the toxicities and recommended dose of PR104 when administered IV to subjects with relapsed/refractory AML and ALL.

Secondary objectives

* Evaluate the pharmacokinetics (PK) of PR104 and a series of PR104 metabolites
* Evaluate any anti-tumor effects of PR104
* Evaluate the expression of AKR1C3 in bone marrow and leukemic cells
* Evaluate potential biomarkers of hypoxia

A single arm study defining the recommended dose of PR104 for each subpopulation in this patient population.

Following informed consent, subjects will undergo baseline evaluation with a history, physical exams, blood work, and disease assessment. Subjects will be assigned a dose of PR104 based on a Bayesian model maintained at the Statistical department at MD Anderson Cancer Center. The model will be updated with both toxicity and efficacy data as it is generated for each subject. New subjects will receive the currently predicted best dose for their respective subset based on prior treatment, age and duration of prior response.

PR104 will be administered initially as induction therapy for up to 3 cycles. Response will be assessed around day 42 (+/- 2 days) of the study. Subjects who obtain a CR or CRp will receive consolidation therapy for up to 4 additional cycles.

Subjects will be evaluated each week during the induction phase of the study. During the consolidation phase of the study, subjects will be evaluated on Day 1 of each cycle and as clinically indicated. Subjects with clinically significant progression will be removed from study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Randomized, Multi-center, Open-label, Study of PR104 Versus PR104/Docetaxel in Non-Small Cell Lung Cancer (NSCLC)	NCT00862134	Non-Small Cell ...	PR104 docetaxel docetaxel Granulocyte col...	18 Years -	Proacta, Incorporated
PR104 and G-CSF in Treating Patients With Solid Tumors	NCT00616213	Unspecified Adu...	filgrastim PR104 F-18-fluoromiso...	18 Years -	Proacta, Incorporated
PR104 in Treating Patients With Previously Untreated or Relapsed Small Cell Lung Cancer	NCT00544674	Lung Cancer	PR104 F-18-fluoromiso...	18 Years -	Proacta, Incorporated
PR104 and G-CSF in Treating Patients With Solid Tumors	NCT00616213	Unspecified Adu...	filgrastim PR104 F-18-fluoromiso...	18 Years -	Proacta, Incorporated
A Phase I Dose Escalation Trial of PR104 Given Weekly in Subjects With Solid Tumors	NCT01358227	Unspecified Adu...	PR104	18 Years -	Proacta, Incorporated
PR104 in Treating Patients With Refractory/Relapsed Acute Leukemia	NCT01037556	Acute Myelogeno... Acute Lymphocyt...	PR104	18 Years -	Proacta, Incorporated

Spots Global Cancer Trial Database for pr104

Every month we try and update this database with for pr104 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pr104

Every month we try and update this database with for pr104 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pr104 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.