A Phase II Study of Androgen Deprivation Therapy With or Without Palbociclib in RB-Positive Metastatic Prostate Cancer

NCT02059213 | Completed Phase 2 Results DMC

• 2 other identifiers: UMCC 2013.117HUM00082715
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 8

Brief Summary

This study will look at the effect of adding the drug Palbociclib to CAD (Combined Androgen Deprivation) therapy in patients with RB (Retinoblastoma Protein) positive hormone sensitive prostate cancer. The investigators hypothesize that the addition of Palbociclib to initial ADT (Androgen Deprivation Therapy) in patients with newly metastatic RB-positive prostate cancer may significantly increase the efficacy of ADT.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients Who Achieve a PSA ≤ 4ng/mL After Seven Months of Protocol Treatment in Each Arm

  The primary analysis will be assessment of the proportion of patients who achieve a (Prostate-specific antigen) PSA \< 4ng/mL after seven months of protocol treatment in each arm.

  28 weeks

Secondary Outcomes (7)

• Number of Participants With Grade >=3 Adverse Events That Are Possibly, Probably or Definitely Related to Study Treatment

  Up to 54 months

• Duration of Therapy

  Up to 54 months

• Proportion of Patients Who Achieve Undetectable PSA (<0.2ng/mL)

  Up to 54 months

• Biochemical Progression-free Survival Rate

  Up to 54 months

• Clinical Progression-free Survival Rate

  Up to 54 months

Study Arms (2)

ADT Alone

ACTIVE COMPARATOR

Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection).

Drug: Bicalutamide; Drug: Zoladex; Drug: Lupron Depot

ADT + Ibrance®

EXPERIMENTAL

Ibrance® (125mg taken daily by mouth days 1-21 of a 28 day cycle) in addition to Androgen Deprivation Therapy (ADT): Bicalutamide (an active non-steroidal antiandrogen; 50mg taken daily by mouth) and Zoladex (LHRH agonist administered by injection), or Lupron Depot (LHRH agonist, administered by injection).

Drug: Ibrance; Drug: Bicalutamide; Drug: Zoladex; Drug: Lupron Depot

Interventions

Ibrance DRUG

Also known as: PD 0332991, Palbociclib

ADT + Ibrance®

Bicalutamide DRUG

Also known as: Casodex

ADT + Ibrance®; ADT Alone

Zoladex DRUG

Also known as: Goserelin acetate implant

ADT + Ibrance®; ADT Alone

Lupron Depot DRUG

Also known as: Leuprolide

ADT + Ibrance®; ADT Alone

Eligibility Criteria

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

You may qualify if:

• Have pathologic diagnosis of prostate cancer.
• Have hormone-sensitive metastatic disease (M1) as evidenced by soft tissue and/or bony metastases.
• Patients may either be untreated for their newly diagnosed metastatic disease (preferred as much as possible) or have started androgen deprivation therapy. Patients who have started androgen deprivation therapy for the treatment of their newly diagnosed metastatic disease are eligible as long as the duration of treatment is less than or equal to 2 weeks (14days) prior to registration. The start date of androgen deprivation is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not the date when an oral antiandrogen started.
• Patients must have a minimum PSA (Prostate-Specific Antigen) ≥ 5 ng/mL within 60 days of registration or prior to the initiation of androgen deprivation for patients who have started androgen deprivation therapy.
• Agree to undergo a biopsy of at least one metastatic site for RB (Retinoblastoma Protein) status evaluation. Adequate metastatic tissue from prior biopsy/resection can be used if available in lieu of a biopsy.
• ECOG performance status of 0-2 (Eastern Cooperative Oncology Group scoring system used to quantify general well-being and activities of daily life; scores range from 0 to 5 where 0 represents perfect health and 5 represents death).
• Patients may have received prior neoadjuvant and/or adjuvant hormonal therapy, for non-metastatic disease but it must not have lasted for more than 36 months. At least 12 months must have elapsed since completion of androgen deprivation therapy in the neoadjuvant and/or adjuvant setting.
• Within 14 days prior to registration patients must have adequate organ and marrow function: White Blood Cell (WBC) count ≥ 3,000/μl, Absolute Neutrophil Count (ANC) ≥ 1,500/μl, Platelet Count ≥ 100,000/μl, Serum Creatinine ≥1.5 x the institutional upper limits of normal or corrected creatinine clearance of ≥ 50 mg/ml/hr/1.73 m2 BSA (Body Surface Area), Bilirubin within the institutional limits of normal, AST (Aspartate Aminotransferase) ≤ 2 x upper limits of normal, ALT (Alanine Aminotransferase) ≤ 2 x upper limits of normal.
• Patients must be able to take oral medication without crushing, dissolving or chewing tablets.
• Patients may have received prior radiation therapy or surgery. However, at least 14 days must have elapsed since completion of radiation therapy or surgery and patient must have only grade 2 or less adverse effects at the time of registration.
• Patients must agree to use highly effective contraception during treatment and for a period of 90 days after ending treatment with PD 0332991.
• Ability to understand and the willingness to sign a written informed consent document that is approved by an institutional review board.

You may not qualify if:

• Patients who have received androgen deprivation therapy for greater than 14 days (LHRH-agonist or antagonist) for the treatment of their newly diagnosed metastatic disease prior to enrollment are not eligible for this study.
• Patients who are currently being treated with strong CYP3A4 inhibitors (e.g., amprenavir, fosamprenavir, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil, miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, verapamil, voriconazole, and grapefruit) or strong inducers (e.g., carbamazepine, felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine and St. John's wort) must either discontinue these drugs or are ineligible.
• Patients must refrain from the use of proton pump inhibitors. If needed, alternative antacid therapies may be used including H2-receptor antagonists, and locally acting antacids.
• Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with a "currently active" second malignancy other than non-melanoma skin cancers are not eligible. Patients are not considered to have a "currently active" malignancy if they have completed all therapy and are now considered without evidence of disease for 1 year.
• HIV-positive patients on combination antiretroviral therapy are ineligible .

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• University of Utah: collaborator
• Vanderbilt-Ingram Cancer Center: collaborator
• Johns Hopkins University: collaborator
• Thomas Jefferson University: collaborator
• Washington University School of Medicine: collaborator
• Northwestern University: collaborator
• City of Hope Comprehensive Cancer Center: collaborator

Study Sites (8)

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

University of Michigan Hospital

Ann Arbor, Michigan, 48109, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Palmbos PL, Daignault-Newton S, Tomlins SA, Agarwal N, Twardowski P, Morgans AK, Kelly WK, Arora VK, Antonarakis ES, Siddiqui J, Jacobson JA, Davenport MS, Robinson DR, Chinnaiyan AM, Knudsen KE, Hussain M. A Randomized Phase II Study of Androgen Deprivation Therapy with or without Palbociclib in RB-positive Metastatic Hormone-Sensitive Prostate Cancer. Clin Cancer Res. 2021 Jun 1;27(11):3017-3027. doi: 10.1158/1078-0432.CCR-21-0024. Epub 2021 Mar 16.

  PMID: 33727260 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

palbociclib; bicalutamide; Goserelin; Leuprolide

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)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Phillip Palmbos, M.D., Ph.D.
• Organization: University of Michigan Rogel Cancer Center

ppalmbos@umich.edu

734-936-3591

Study Officials

• Maha Hussain, MD, FACP, FASCO

  University of Michigan Comprehensive Cancer Center and Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2014
• First Posted: February 11, 2014
• Study Start: June 1, 2014
• Primary Completion: September 9, 2017
• Study Completion: June 4, 2019
• Last Updated: September 16, 2020
• Results First Posted: January 28, 2019

Record last verified: 2020-08

Locations

US (8)