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Testing the Addition of a New Anti-Cancer Drug, Niraparib, to the Usual Treatment (Hormone and Radiation Therapy) for Prostate Cancer with a High Chance of Recurring

Status
Temporarily Closed
Cancer Type
Prostate Cancer
Unknown Primary
Trial Phase
Phase I
Phase II
Eligibility
18 Years and older, Male
Study Type
Treatment
NCT ID
NCT04037254
Protocol IDs
NRG-GU007 (primary)
NRG-GU007
NCI-2019-02260
Study Sponsor
NRG Oncology

Summary

This is a phase I-II trial to find the safety and activity of adding a new drug (neratinib) to the usual treatment (radiation combined with male hormone deprivation therapy) in lowering the chance of prostate cancer growing or returning. Niraparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Adding niraparib to the usual care may lower the chance of prostate cancer growing or returning.

Objectives

PRIMARY OBJECTIVES:
I. To establish the preferred dose of niraparib in combination with radiation and antiandrogen therapy (ADT). (Phase I)
II. To compare the disease-free state, defined as prostate specific antigen (PSA) remaining < 0.1 ng/ml at the end of ADT therapy in men with high risk prostate cancer treated with standard therapy with or without the addition of niraparib. (Phase IIR)

SECONDARY OBJECTIVES:
I. To further establish the safety and toxicity profile of standard treatment with radiation and androgen deprivation therapy specifically, two years from initiation of ADT, plus niraparib at the phase II dose.
II. To compare the overall survival, prostate cancer-specific survival, local/regional or distant progression, and distant metastatic disease rates of standard therapy with or without the addition of niraparib.

EXPLORATORY OBJECTIVE:
I. To identify genomic biomarkers of response to combination therapy with radiation, ADT and PARP inhibition.

OUTLINE: This is a phase I, dose-escalation study of niraparib, followed by a randomized phase II study.

PHASE I: Patients receive niraparib orally (PO) once daily (QD) and receive standard of care gonadotrophin releasing hormone (GnRH) agonist androgen suppression therapy. Treatment with niraparib continues for 12 months, and GnRH agonist therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib and GnRH agonist, patients undergo standard of care intensity-modulated radiation therapy (IMRT) 5 days per week for about 6-9 weeks, depending on type of radiation therapy given, in the absence of disease progression or unacceptable toxicity. Patients also undergo magnetic resonance imaging (MRI) on study.

PHASE II: Patients are randomized to 1 of 2 arms:

ARM I: Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months in the absence of disease progression or unacceptable toxicity. Beginning 8-28 weeks after starting GnRH agonist, patients undergo IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study.

ARM II: Patients undergo standard of care GnRH agonist androgen suppression therapy for 24 months, and niraparib PO QD for 12 months in the absence of disease progression or unacceptable toxicity. Beginning 8 weeks after starting niraparib, patients undergo standard of care IMRT 5 days per week for about 6-9 weeks depending on type of radiation therapy given in the absence of disease progression or unacceptable toxicity. Patients also undergo MRI on study.

After completion of study treatment, patients are followed up every 6 months for 3 years, then annually for 3 years.

Eligibility

  1. Histologically confirmed (within 180 days prior to registration) adenocarcinoma of the prostate at high risk for recurrence as determined by the following criteria, according to American Joint Committee on Cancer (AJCC) 8th edition: * Phase I enrollment ** Gleason >= 9, PSA =< 150 ng/mL, any T-stage * Phase II enrollment ** Gleason >= 9, PSA =< 150 ng/mL, any T-stage ** Gleason 8, PSA < 20 ng/mL, and >= T2 ** Gleason 8, PSA >= 20-150 ng/mL, any T-stage ** Gleason 7, PSA >= 20-150 ng/mL, any T-stage
  2. No distant metastases as evaluated by: * Bone scan 90 days prior to registration * Lymph node assessment by computed tomography (CT) or magnetic resonance (MR) of pelvis or nodal sampling within 90 days prior to registration (Please note: Lymph nodes will be considered negative [N0] if they are < 1.5 cm short axis)
  3. History/physical examination within 90 days prior to registration
  4. Age >= 18
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 180 days prior to registration
  6. Pretreatment serum PSA, obtained prior to any androgen suppression therapy and within 180 days of registration
  7. Phase I patients: Prior androgen suppression for prostate cancer is not allowed prior to registration
  8. Phase II patients: Prior androgen suppression for prostate cancer is allowed =< 45 days prior to registration
  9. Hemoglobin >= 9.0 g/dL (within 90 days prior to registration)
  10. Platelets >= 100,000 cells/mm^3 (within 90 days prior to registration)
  11. Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (within 90 days prior to registration)
  12. Serum creatinine =<1.5 x upper limit of normal (ULN) OR a calculated creatinine clearance >= 30 mL/min estimated using Cockcroft-Gault equation (within 90 days prior to registration)
  13. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x ULN (within 90 days prior to registration)
  14. Serum albumin >= 3 g/dL (within 90 days prior to registration)
  15. Serum potassium >= 3.5 mmol/L (within 90 days prior to registration)
  16. Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< 1 x ULN (Note: in subjects with Gilberts syndrome, if total bilirubin is > 1.5 x ULN, measure direct and indirect bilirubin, and if direct bilirubin is =< 1.5 x ULN, subject may be eligible) (within 90 days prior to registration)
  17. Men of child-producing potential must be willing to consent to use effective contraception while on treatment and for at least 3 months afterwards
  18. The patient or a legally authorized representative must provide study-specific informed consent prior to study entry

Treatment Sites in Georgia

Emory Saint Joseph's Hospital


5665 Peachtree Dunwoody Road NE
Atlanta, GA 30342
www.emoryhealthcare.org

Emory University Hospital - Atlanta


1364 Clifton Road NE
Atlanta, GA 30322
www.emoryhealthcare.org

Grady Memorial Hospital


80 Jesse Hill Jr. Drive, SE
Atlanta, GA 30303
www.gradyhealth.org

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.
Georgia CORE

 

Advancing Cancer Care through Partnerships and Innovation

Georgia CORE is a statewide nonprofit that leverages partnerships and innovation to attract more clinical trials, increase research, and promote education and early detection to improve cancer care for Georgians in rural, urban, and suburban communities across the state.