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Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer

Primary Purpose

Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
oxaliplatin
pemetrexed disodium
questionnaire administration
laboratory biomarker analysis
reverse transcriptase-polymerase chain reaction
polymorphism analysis
Sponsored by
University of Southern California
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hormone-resistant Prostate Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed prostate cancer
  • Measurable disease on computed tomography (CT) or evaluable disease on bone scan with an elevated PSA
  • For patients who did not initially present with metastatic disease, definitive treatment with either radical prostatectomy or external beam radiation is permitted
  • Documented progression on (a) two prior hormone treatments AND (b) one or two chemotherapy regimens
  • Documented progression on two prior hormone therapies is defined as orchiectomy followed by anti-adrenal medication upon progression OR gonadotropin-releasing hormone (GnRH) analog +/- androgen receptor blocker with addition or subtraction upon progression; castrate level of testosterone must be documented at study entry
  • Documented progression on taxane-based chemotherapy; in addition, patients may have failed a second prior chemotherapy regimen
  • Palliative radiation therapy for metastatic disease is allowed only if less than 25% of total body bone marrow was irradiated; 28 days must have elapsed since completion of radiation therapy (RT) with bone marrow recovery; soft tissue disease irradiated in the prior 2 months may not be designated as measurable disease
  • ECOG performance score of 0-2
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelet count >= 100,000/uL
  • Creatinine clearance >= 45 mL/min
  • Serum total bilirubin =<1.5 mg/dL
  • Alkaline phosphatase =< 3x the upper limit of normal (ULN) for the reference lab (=< 5x the ULN for patients with known hepatic metastases) and no upper limit for patients with known bone metastases
  • Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) =< 3x the ULN for the reference lab (=< 5x the ULN for patients with known hepatic metastases)
  • Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy
  • Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial
  • Men of childbearing potential must consent to use barrier contraception while on treatment and for 90 days thereafter
  • Patients with pleural or peritoneal effusions are eligible
  • Willingness and ability to take vitamin supplementation and steroid premedication as specified in protocol
  • Patients with superficial bladder cancer or skin cancer who have second malignancy within 5 years which was removed with curative intent

Exclusion Criteria:

  • Active infection or with a fever >= 38.5 degrees Celsius (C) within 3 days of the first scheduled protocol treatment
  • Patients with brain metastases
  • Prior malignancy within the past 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or superficial bladder cancer
  • Known hypersensitivity to any of the components of oxaliplatin or pemetrexed
  • Received radiotherapy to more than 25% of their bone marrow, or patients who received any radiotherapy within 4 weeks of entry
  • Received treatment with strontium
  • Receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment
  • Life expectancy < 6 months
  • Peripheral neuropathy >= Grade 2
  • Any other medical condition, including mental illness or substance abuse
  • History of allogeneic transplant
  • Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated, or both)
  • Inability to stop nonsteroidal anti-inflammatory drugs (NSAIDS) for a period of 2 days before, the day of, and 2 days following administration of Alimta; 5 days before, the day of, and 2 days following administration of Alimta for long-acting NSAIDS

Sites / Locations

  • USC/Norris Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (chemotherapy and enzyme inhibitor)

Arm Description

Patients receive oxaliplatin IV over 2 hours and pemetrexed disodium IV on day 1. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Best Overall Response
For patients with measurable disease, the RECIST 1.0 criteria was used to determine response. Complete Response = disappearance of all target lesions, Partial Response = greater or equal to 30% decrease in sum of longest diameter or target lesions, Stable Disease = <30% decrease or <20% increase, Progressive Disease = greater or equal to 20% increase in longest diameter of target lesions. For patients who do not have measurable disease by RECIST, the response was based on PSA response defined by Prostate Cancer Working Group criteria (1999) as 50% reduction in PSA confirmed on a second measurement at least 4 weeks later.

Secondary Outcome Measures

Time to Disease Progression and Overall Survival
Progression-free survival was defined as the time from the first infusion of study treatment to the date of radiographic disease progression according to RECIST 1.0, or until two consecutive PSA rises occurred with an absolute increase of 5 ng/mL and a 50% relative increase over baseline. For patients without documented disease progression, the date of death or last follow-up without disease progression was used.
Number of Participants With Serious Adverse Events (SAEs)
Safety evaluation according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Full Information

First Posted
April 15, 2011
Last Updated
February 5, 2014
Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01338792
Brief Title
Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer
Official Title
A Phase II Trial of Oxaliplatin and Pemetrexed in Hormone Refractory Prostate Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
February 2014
Overall Recruitment Status
Completed
Study Start Date
June 2006 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Southern California
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies how well giving oxaliplatin and pemetrexed disodium together works in treating patients with refractory hormone-resistant prostate cancer. Drugs used in chemotherapy, such as oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pemetrexed disodium may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving oxaliplatin together with pemetrexed disodium may kill more tumor cells.
Detailed Description
PRIMARY OBJECTIVES: I. To determine the response rate by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, prostate-specific antigen (PSA) response by the PSA Working Group criteria, and overall clinical benefit defined by summation of RECIST complete responses (CR) plus RECIST partial responses (PR) plus PSA PRs. SECONDARY OBJECTIVES: I. To determine time to progression in patients with hormone-refractory prostate cancer (HRPC) receiving oxaliplatin and pemetrexed. II. To describe the safety profile of this treatment. III. Pain response will be evaluated in an exploratory manner. IV. Undertake a pilot analysis of excision repair cross-complementing 1 (ERCC1) expression levels and polymorphisms, looking at their ability to predict response to platinum therapy. OUTLINE: Patients receive oxaliplatin intravenously (IV) over 2 hours and pemetrexed disodium IV on day 1. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hormone-resistant Prostate Cancer, Recurrent Prostate Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (chemotherapy and enzyme inhibitor)
Arm Type
Experimental
Arm Description
Patients receive oxaliplatin IV over 2 hours and pemetrexed disodium IV on day 1. Courses repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
pemetrexed disodium
Other Intervention Name(s)
ALIMTA, LY231514, MTA
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
questionnaire administration
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
reverse transcriptase-polymerase chain reaction
Other Intervention Name(s)
RT-PCR
Intervention Description
Correlative studies
Intervention Type
Genetic
Intervention Name(s)
polymorphism analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Best Overall Response
Description
For patients with measurable disease, the RECIST 1.0 criteria was used to determine response. Complete Response = disappearance of all target lesions, Partial Response = greater or equal to 30% decrease in sum of longest diameter or target lesions, Stable Disease = <30% decrease or <20% increase, Progressive Disease = greater or equal to 20% increase in longest diameter of target lesions. For patients who do not have measurable disease by RECIST, the response was based on PSA response defined by Prostate Cancer Working Group criteria (1999) as 50% reduction in PSA confirmed on a second measurement at least 4 weeks later.
Time Frame
RECIST evaluation: Baseline, after every 2 courses, and then every 6 months after off-study, up to 1 year. PSA evaluation: baseline, day 1 of each course, final evaluation, and then every 6 months after off-study, up to 1 year
Secondary Outcome Measure Information:
Title
Time to Disease Progression and Overall Survival
Description
Progression-free survival was defined as the time from the first infusion of study treatment to the date of radiographic disease progression according to RECIST 1.0, or until two consecutive PSA rises occurred with an absolute increase of 5 ng/mL and a 50% relative increase over baseline. For patients without documented disease progression, the date of death or last follow-up without disease progression was used.
Time Frame
Baseline, after every 2 courses, and then every 6 months after off-study (RECIST) until progression; or baseline, day 1 of each course, at the final evaluation, and then every 6 months after off-study (PSA) until progression
Title
Number of Participants With Serious Adverse Events (SAEs)
Description
Safety evaluation according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time Frame
Baseline, days 1 and 7 of each course, and at last evaluation, up to 1 year

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histologically confirmed prostate cancer Measurable disease on computed tomography (CT) or evaluable disease on bone scan with an elevated PSA For patients who did not initially present with metastatic disease, definitive treatment with either radical prostatectomy or external beam radiation is permitted Documented progression on (a) two prior hormone treatments AND (b) one or two chemotherapy regimens Documented progression on two prior hormone therapies is defined as orchiectomy followed by anti-adrenal medication upon progression OR gonadotropin-releasing hormone (GnRH) analog +/- androgen receptor blocker with addition or subtraction upon progression; castrate level of testosterone must be documented at study entry Documented progression on taxane-based chemotherapy; in addition, patients may have failed a second prior chemotherapy regimen Palliative radiation therapy for metastatic disease is allowed only if less than 25% of total body bone marrow was irradiated; 28 days must have elapsed since completion of radiation therapy (RT) with bone marrow recovery; soft tissue disease irradiated in the prior 2 months may not be designated as measurable disease ECOG performance score of 0-2 Absolute neutrophil count (ANC) >= 1500/uL Platelet count >= 100,000/uL Creatinine clearance >= 45 mL/min Serum total bilirubin =<1.5 mg/dL Alkaline phosphatase =< 3x the upper limit of normal (ULN) for the reference lab (=< 5x the ULN for patients with known hepatic metastases) and no upper limit for patients with known bone metastases Serum glutamic oxaloacetic transaminase (SGOT)/serum glutamic pyruvic transaminase (SGPT) =< 3x the ULN for the reference lab (=< 5x the ULN for patients with known hepatic metastases) Patients must be recovered from both acute and late effects of any prior surgery, radiotherapy or other antineoplastic therapy Patients or their legal representatives must be able to read, understand and provide informed consent to participate in the trial Men of childbearing potential must consent to use barrier contraception while on treatment and for 90 days thereafter Patients with pleural or peritoneal effusions are eligible Willingness and ability to take vitamin supplementation and steroid premedication as specified in protocol Patients with superficial bladder cancer or skin cancer who have second malignancy within 5 years which was removed with curative intent Exclusion Criteria: Active infection or with a fever >= 38.5 degrees Celsius (C) within 3 days of the first scheduled protocol treatment Patients with brain metastases Prior malignancy within the past 5 years, except for curatively treated basal cell or squamous cell carcinoma of the skin or superficial bladder cancer Known hypersensitivity to any of the components of oxaliplatin or pemetrexed Received radiotherapy to more than 25% of their bone marrow, or patients who received any radiotherapy within 4 weeks of entry Received treatment with strontium Receiving concurrent investigational therapy or who have received investigational therapy within 30 days of the first scheduled day of protocol treatment Life expectancy < 6 months Peripheral neuropathy >= Grade 2 Any other medical condition, including mental illness or substance abuse History of allogeneic transplant Known human immunodeficiency virus (HIV) or Hepatitis B or C (active, previously treated, or both) Inability to stop nonsteroidal anti-inflammatory drugs (NSAIDS) for a period of 2 days before, the day of, and 2 days following administration of Alimta; 5 days before, the day of, and 2 days following administration of Alimta for long-acting NSAIDS
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jacek Pinski
Organizational Affiliation
University of Southern California
Official's Role
Principal Investigator
Facility Information:
Facility Name
USC/Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24099865
Citation
Dorff TB, Tsao-Wei DD, Groshen S, Boswell W, Goldkorn A, Xiong S, Quinn DI, Pinski JK. Efficacy of oxaliplatin plus pemetrexed in chemotherapy pretreated metastatic castration-resistant prostate cancer. Clin Genitourin Cancer. 2013 Dec;11(4):416-22. doi: 10.1016/j.clgc.2013.07.011. Epub 2013 Oct 4.
Results Reference
derived

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Oxaliplatin and Pemetrexed Disodium in Treating Patients With Refractory Hormone-Resistant Prostate Cancer

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