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

NCT01051570 | Completed Phase 2 Results DMC

• 4 other identifiers: CDR0000663630P30CA022453WSU-2009-087NOVARTIS-WSU-2009-087
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Time to Progression (TTP)

  Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

  Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease.

Secondary Outcomes (5)

• Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria

  Day 1 of each cycle (every 21 days), through study completion, an average of 6 months

• PSA Response Rate

  Day 1 of each cycle (every 21 days), through study completion, an average of 6 months

• Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6)

  Archival tissue will be collected if available. Optional biopsies pre-treatment and 24 hours after first everolimus and carboplatin dose

• Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample.

  Samples were collected Cycle 2, Day 1

• Overall Survival

  After treatment, participants will be contacted every 3 months up to 4 years

Study Arms (1)

Carboplatin, RAD 001 & Prednisone

EXPERIMENTAL

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

Drug: carboplatin; Drug: RAD 001; Drug: prednisone; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

carboplatin DRUG

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

Also known as: Paraplatin®

Carboplatin, RAD 001 & Prednisone

RAD 001 DRUG

5 mg orally starting on Day 2 then continuous

Also known as: Afinitor®, Zortress, Everolimus

Carboplatin, RAD 001 & Prednisone

prednisone DRUG

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

Also known as: Deltasone, Liquid Pred, Meticorten, Orasone, Prednicen-M, Prednicot, Sterapred, Sterapred DS

Carboplatin, RAD 001 & Prednisone

laboratory biomarker analysis OTHER

Samples will be collected from archival tissue.

Carboplatin, RAD 001 & Prednisone

pharmacological study OTHER

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

Carboplatin, RAD 001 & Prednisone

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed metastatic adenocarcinoma of the prostate * Objective disease progression or rising PSA despite androgen deprivation therapy and antiandrogen withdrawal (when applicable) * Progressed after ≥ 1 prior docetaxel-based chemotherapy regimen for metastatic disease * Patients with measurable disease\* must have either rising PSA, increase in size of the lesion(s), or both * Patients with rising PSA as the only evidence of disease progression must demonstrate a rising trend with 2 successive elevations ≥ 1 week apart * Patients with no measurable disease must have a PSA ≥ 5 ng/mL or new areas of bony metastases on bone scan NOTE: \*There is no minimum PSA requirement for patients with measurable disease * Documented to be castrate with a testosterone level of ≤ 0.5 ng/mL * Leuteinizing hormone-releasing hormone agonist therapy must be continued, if required to maintain castrate levels of testosterone * No uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases PATIENT CHARACTERISTICS: * Zubrod performance status 0-1 * ANC ≥ 1,500/mm\^3 * Hemoglobin ≥ 9.0 g/dL * Platelet count ≥ 100,000/mm\^3 * Total bilirubin ≤ 1.5 times upper limit of normal (ULN) * Calculated creatinine clearance ≥ 50 mL/min OR serum creatinine ≤ 2 mg/dL * AST and/or ALT ≤ 2.5 times ULN if alkaline phosphatase normal OR alkaline phosphatase ≤ 4 times ULN if AST and/or ALT normal (for patients without documented bone metastases or for patients with liver metastases) * AST and/or ALT \< 2.5 times ULN, without regard to alkaline phosphatase levels (for patients with documented bone metastases) * Fasting serum cholesterol ≤ 300 mg/dL OR ≤ 7.75 mmol/L AND fasting triglycerides ≤ 2.5 times ULN (in the case that one or both of these thresholds are exceeded, the patient is eligible only after initiation of appropriate lipid-lowering medication) * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Barbara Ann Karmanos Cancer Institute: lead
• National Cancer Institute (NCI): collaborator

Study Sites (4)

Northshore University Health System

Evanston, Illinois, 60201, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201-1379, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Related Publications (1)

• 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.

  PMID: 26375845 DERIVED

Related Links

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

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Carboplatin; Everolimus; Prednisone

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Sirolimus; Macrolides; Lactones; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Limitations and Caveats

Small sample size; Correlates were conducted in \<50% of the patients.

Results Point of Contact

• Title: Elisabeth I. Heath M.D.
• Organization: Barbara Ann Karmanos Cancer Institute

vaishamu@karmanos.org

313-576-8717

Study Officials

• Ulka N. Vaishampayan, M.D.

  Barbara Ann Karmanos Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 15, 2010
• First Posted: January 18, 2010
• Study Start: February 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: December 1, 2020
• Results First Posted: August 25, 2014

Record last verified: 2020-11

Locations

US (4)