Carboplatin, Everolimus, and Prednisone in Treating Patients With Metastatic Prostate Cancer That Progressed After Docetaxel

NCT ID: NCT01051570

Last Updated: 2020-12-01

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-02-28

Study Completion Date

2013-09-30

Brief Summary

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RATIONALE: Drugs used in chemotherapy, such as carboplatin and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving carboplatin together with everolimus and prednisone may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving carboplatin together with everolimus and prednisone works in treating patients with metastatic prostate cancer that progressed after docetaxel.

Detailed Description

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OBJECTIVES:

Primary

* To evaluate the time to progression (TTP) achieved with carboplatin and everolimus in patients with castrate resistant metastatic prostate cancer that progressed after docetaxel-based chemotherapy.

Secondary

* To evaluate the safety of this regimen.
* To assess the PSA response rate in patients treated with this regimen.
* To evaluate the overall survival (OS) outcome in these patients.
* To investigate the association of TTP and PSA response rate with correlative markers, such as phospho mTOR, pAKT, and p70S6.
* To evaluate the pharmacokinetics of this regimen.
* To explore the association of TTP, OS, and circulating tumor tumor cell count.

OUTLINE: Patients receive carboplatin IV over 30-60 minutes on day 1, oral prednisone twice daily on days on days 1-21, and oral everolimus once daily on days 2-21 of course 1 and on days 1-21 of subsequent courses. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Blood and tumor tissue samples are collected periodically for pharmacodynamic, pharmacokinetic, and biomarker analysis.

After completion of study treatment, patients are followed up every 3 months.

Conditions

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Prostate Cancer

Keywords

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hormone-resistant prostate cancer recurrent prostate cancer stage IV prostate cancer adenocarcinoma of the prostate

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Carboplatin, RAD 001 & Prednisone

Carboplatin: AUC=4 by Calvert's formula (max dose 600 mg)\*IV over 30-60 min, Day 1 of a 21 day cycle

RAD 001: 5 mg Orally daily, starting from Day 2 continuously

Prednisone 5 mg Orally twice daily, continuously

Group Type EXPERIMENTAL

carboplatin

Intervention Type DRUG

AUC = 5 by Calvert's formula, day 1 of each 21 day cycle

RAD 001

Intervention Type DRUG

5 mg orally starting on Day 2 then continuous

prednisone

Intervention Type DRUG

5 mg orally twice a day starting on Day 1 then continuous

laboratory biomarker analysis

Intervention Type OTHER

Samples will be collected from archival tissue.

pharmacological study

Intervention Type OTHER

Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2

Interventions

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carboplatin

AUC = 5 by Calvert's formula, day 1 of each 21 day cycle

Intervention Type DRUG

RAD 001

5 mg orally starting on Day 2 then continuous

Intervention Type DRUG

prednisone

5 mg orally twice a day starting on Day 1 then continuous

Intervention Type DRUG

laboratory biomarker analysis

Samples will be collected from archival tissue.

Intervention Type OTHER

pharmacological study

Samples will be collected Cycle 1, day 1, 2 \& 8 and Cycle 2, Day 1 \& 2

Intervention Type OTHER

Other Intervention Names

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Paraplatin® Afinitor® Zortress Everolimus Deltasone Liquid Pred Meticorten Orasone Prednicen-M Prednicot Sterapred Sterapred DS

Eligibility Criteria

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Inclusion Criteria

* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment
* Willing and able to comply with this study
* Able to ingest oral medication
* No other malignancies except non-melanoma skin cancer or any other adequately treated cancer in complete remission for ≥ 2 years
* No significant traumatic injury within the past 4 weeks
* No active (acute or chronic) or uncontrolled severe infections
* No severe and/or uncontrolled medical conditions or other conditions that could affect study participation, including the following:

* NYHA class III-IV symptomatic congestive heart failure
* Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within the past 6 months, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
* Severely impaired lung function as defined by spirometry and DLCO that is 50% of the normal predicted value and/or oxygen saturation that is ≤ 88% at rest on room air
* Uncontrolled diabetes as defined by fasting serum glucose \> 1.5 times ULN
* Liver disease such as cirrhosis, chronic active hepatitis, or chronic persistent hepatitis
* Known history of HIV seropositivity, hepatitis B or C
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
* Active, bleeding diathesis
* No known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to their excipients
* No history of noncompliance to medical regimens
* No uncontrolled diabetes mellitus

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* At least 1 prior docetaxel based regimen for metastatic disease

* Docetaxel based combination therapy or docetaxel alone considered as 1 regimen
* No more than 2 prior chemotherapy regimens for metastatic disease
* No prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
* At least 6 weeks since prior bicalutamide or nilutamide
* At least 4 weeks since prior flutamide
* More than 4 weeks since prior and no other concurrent investigational drugs
* More than 4 weeks since prior and no other concurrent anticancer therapies (including chemotherapy, radiotherapy, or antibody-based therapy)
* More than 4 weeks since prior and no concurrent major surgery (defined as requiring general anesthesia) and recovered
* More than 1 week since prior and no concurrent immunization with attenuated live vaccines
* No concurrent chronic, systemic treatment with corticosteroids or other immunosuppressive agents

* Topical or inhaled corticosteroids are allowed
* No concurrent prophylactic growth factors
* Concurrent bisphosphonate therapy allowed
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role lead

Responsible Party

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Elisabeth Heath

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ulka N. Vaishampayan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

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Northshore University Health System

Evanston, Illinois, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, United States

Site Status

Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status

Countries

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United States

References

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Vaishampayan U, Shevrin D, Stein M, Heilbrun L, Land S, Stark K, Li J, Dickow B, Heath E, Smith D, Fontana J. Phase II Trial of Carboplatin, Everolimus, and Prednisone in Metastatic Castration-resistant Prostate Cancer Pretreated With Docetaxel Chemotherapy: A Prostate Cancer Clinical Trial Consortium Study. Urology. 2015 Dec;86(6):1206-11. doi: 10.1016/j.urology.2015.08.008. Epub 2015 Sep 12.

Reference Type DERIVED
PMID: 26375845 (View on PubMed)

Related Links

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http://cancer.gov/clinicaltrials

Clinical trial summary from the National Cancer Institute's PDQ® database

Other Identifiers

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P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-2009-087

Identifier Type: -

Identifier Source: secondary_id

NOVARTIS-WSU-2009-087

Identifier Type: -

Identifier Source: secondary_id

CDR0000663630

Identifier Type: -

Identifier Source: org_study_id