Neoadjuvant Androgen Deprivation, Darolutamide, and Ipatasertib in Men With Localized, High Risk Prostate Cancer

NCT04737109 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: BTCRC-GU19-404
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 3

Brief Summary

This multicenter Phase I/II trial consists of two stages: a phase I stage in patients with castration resistant prostate cancer in which the recommended phase II dose will be determined for ipatasertib administered in combination with darolutamide; and a phase II neoadjuvant stage in which patients with high risk prostate cancer and loss of PI3K pathway activation in the tumor tissue planning on undergoing prostatectomy receive ADT, darolutamide, and ipatasertib for 24 weeks prior to planned surgery.

Conditions

Castrate Resistant Prostate Cancer

Keywords

prostate cancer; high risk; neoadjuvant; PTEN loss; darolutamide; ipatasertib

Outcome Measures

Primary Outcomes (1)

• Phase II: Pathological Complete Response (pCR) Rate

  Combined rate of pathologic complete response (pCR) (defined as absence of pathologic disease on hematoxylin and eosin (H\&E) stain (ypT0)), or with presence of minimal residual disease (\<5 mm linearly)

  From C1D1 until death.

Secondary Outcomes (3)

• Summary of Dose-Limiting Toxicities

  Until the completion of cycle 1, 28 days

• Phase II - Two Year Biochemical Recurrence-free Survival

  From C1D1 until death or up to a maximum of 24 months

• Phase II: Rate of PSA0

  From C1D1 until death.

Study Arms (2)

Phase I De-Escalation Cohort: ADT + Ipatasertib + Darolutamide

EXPERIMENTAL

Cycle 0 Days 1-7: Ipatasertib Monotherapy + Androgen Deprivation Therapy (ADT) Cycle 1+: Ipatasertib + Darolutamid + ADT

Drug: Ipatasertib; Drug: Darolutamide; Drug: Androgen Deprivation Therapy

Phase II: ADT + Ipatasertib + Darolutamide

EXPERIMENTAL

All Cycles: Ipatasertib + Darolutamide + ADT

Drug: Ipatasertib; Drug: Darolutamide; Drug: Androgen Deprivation Therapy

Interventions

Ipatasertib DRUG

Ipatasertib

Phase I De-Escalation Cohort: ADT + Ipatasertib + Darolutamide; Phase II: ADT + Ipatasertib + Darolutamide

Darolutamide DRUG

Darolutamide

Phase I De-Escalation Cohort: ADT + Ipatasertib + Darolutamide; Phase II: ADT + Ipatasertib + Darolutamide

Androgen Deprivation Therapy DRUG

ADT per institutional standards

Also known as: ADT

Phase I De-Escalation Cohort: ADT + Ipatasertib + Darolutamide; Phase II: ADT + Ipatasertib + Darolutamide

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Subject's must be biologically male to participate in this study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed prostate cancer
• Male and \>= 18 years of age
• ECOG performance status of \<= 2
• Castration resistant prostate cancer, defined as biochemical, radiographic, and/or clinical progression despite castrate level of testosterone (\<50 ng/dL). There is no restriction on prior therapies for CRPC.
• Evaluable disease, with PSA \>= 1.0 ng/ml (nmCRPC) or visible prostate cancer on imaging (mCRPC).
• Serum testosterone \< 50 ng/dL
• Willing to undergo blood draws to measure PK levels
• Able to swallow pills
• Must have ability to understand and the willingness to sign a written informed consent prior to receiving a subject ID number.
• Unless surgically sterile, sexually active patients must agree to use effective barrier method and refrain from sperm donation during the study treatment and for 3 months after the end of study treatment.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study
• Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 14 days prior to registration.
• Hematological
• Hemoglobin (Hgb): \>/= 9 g/dL
• Absolute Neutrophil Count (ANC): \>/= 1,500/uL

You may not qualify if:

• Patients receiving systemic therapy for prostate cancer \<= 21 days or 5 half-lives (whichever is shorter) prior to starting study drug are not eligible.
• NOTE: Patients must continue Androgen Deprivation Therapy, and patients can receive bone supportive therapy.
• Histology of small cell carcinoma prostate cancer. Adenocarcinoma with neuroendocrine features is allowed.
• Any active infection requiring IV antibiotics
• Known additional malignancy that has a life-expectancy \< 2 years.
• Clinically significant acute infection requiring systemic antibacterial, antifungal, or antiviral therapy including:
• hepatitis B (known positive HBV surface antigen (HBsAg) result),
• hepatitis C, or
• human immunodeficiency virus (positive HIV 1/2 antibodies). ---NOTES: Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. Subjects with HIV/AIDS with adequate antiviral therapy to control viral load would be allowed if they are stable and have been on treatment for \>= 4 weeks prior to first dose of study drug(s). Subjects with viral hepatitis with controlled viral load would be allowed while on suppressive antiviral therapy.
• History of type I or type II diabetes mellitus requiring insulin.
• Any of the following within 6 months before registration: stroke, myocardial infarction, severe/unstable anginal pectoris, coronary/peripheral artery bypass graft, congestive heart failure New York Heart Association (NYHA) class III or IV.
• Congenital long QT syndrome or QTcF \> 480 milliseconds
• Grade \>= 2 uncontrolled or untreated hypercholesterolemia (\>300 mg/dL) or hypertriglyceridemia (\>300 mg/dL)
• History of or active inflammatory bowel disease (IBD) or active bowel inflammation (diverticulitis)
• Lung disease: pneumonitis, interstitial lung disease, idiopathic pulmonary fibrosis, cystic fibrosis, Aspergillosis, active tuberculosis, or history of opportunistic infections (pneumocystis pneumonia or cytomegalovirus pneumonia)

Sponsors & Collaborators

• David VanderWeele: lead

Study Sites (3)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

ipatasertib; darolutamide; Androgen Antagonists

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)

Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• David VanderWeele, MD\Phd

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor, Medicine - Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Study Record Dates

• First Submitted: January 29, 2021
• First Posted: February 3, 2021
• Study Start: July 13, 2021
• Primary Completion: August 15, 2022
• Study Completion: August 15, 2022
• Last Updated: November 13, 2023
• Results First Posted: November 13, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)