Testing Two Oral Drugs Combination (Cediranib and Olaparib) Compared to a Single Drug (Olaparib) for Men With Advanced Prostate Cancer

NCT02893917 | Active Not Recruiting Phase 2 Results FDA Drug

• 4 other identifiers: NCI-2016-0134620000204619984UM1CA186689
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 16

Brief Summary

This randomized phase II trial studies how well olaparib with or without cediranib works in treating patients with castration-resistant prostate cancer that has spread to other places in the body (metastatic). PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as olaparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Cediranib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving olaparib and cediranib may help treat patients with castration-resistant prostate cancer.

Conditions

Prostate Adenocarcinoma With Neuroendocrine Differentiation; Metastatic Prostate Carcinoma; Stage IV Prostate Adenocarcinoma AJCC v7; Metastatic Prostate Adenocarcinoma With Neuroendocrine Differentiation; Advanced Prostate Adenocarcinoma With Neuroendocrine Differentiation; Castration-Resistant Prostate Carcinoma

Outcome Measures

Primary Outcomes (1)

• Radiographic Progression Free Survival

  The two study arms will be compared for radiographic progression free survival with Kaplan-Meier estimates and log-rank tests. The Rothman confidence interval, which is based on Greenwood's variance, Thomas and Grunkemeier confidence interval, and the simultaneous confidence bands by Nair and Hall and Wellner, will be reported. In addition, the possible confounding variables will be compared for survival with log-rank test.

  Time interval from random assignment to the date when the first site of disease is found to progress, or death, whichever occurs first, assessed up to 5 years

Secondary Outcomes (6)

• Overall Survival

  Time between randomization and death due to any cause (or last contact for surviving patients and those lost to follow-up), assessed up to 5 years

• Objective Response Rate

  Up to 5 years

• Prostate-specific Antigen Response Rate

  Up to 5 years

• Correlation Between Homologous Recombination Deficiency Status and Radiographic Progression Free Survival

  Up to 1 week prior to start of therapy

• Incidence of Genomic Alterations

  Up to 5 years

Other Outcomes (2)

• Baseline Predictive Biomarkers by Plasma Angiome

  Baseline

• On-treatment Markers of Acquired Resistance by Plasma Angiome

  Up to 5 years

Study Arms (2)

Arm A (olaparib, cediranib)

EXPERIMENTAL

Patients receive olaparib PO BID and cediranib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cediranib; Drug: Olaparib

Arm B (olaparib)

ACTIVE COMPARATOR

Patients receive olaparib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Olaparib

Interventions

Cediranib DRUG

Given PO

Also known as: AZ-D2171, AZD 2171, AZD2171

Arm A (olaparib, cediranib)

Olaparib DRUG

Given PO

Also known as: AZD 2281, AZD-2281, AZD2281, KU 0059436, KU-0059436, KU0059436, Lynparza, Olanib, Olaparix, PARP Inhibitor AZD2281

Arm A (olaparib, cediranib); Arm B (olaparib)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed progressive, metastatic castration resistant prostate adenocarcinoma by meeting ALL the following:
• Pathology of prostate gland or metastatic disease must confirm the diagnosis of prostate adenocarcinoma; mixed histology with other variants including but not limited to small cell or neuroendocrine differentiation must be discussed with the study principal investigator (PI)
• Metastasis must be documented by radiographic evidence
• Castration resistance must be documented with surgical or medical castration with serum testosterone \< 50 ng/dL (\< 2.0 nM); if the patient is being treated with luteinizing hormone-releasing hormone (LHRH) agonists (patient who has not undergone orchiectomy), this therapy must have been initiated at least 4 weeks prior to cycle 1, day 1 and must be continued throughout the study
• Progression must be evidenced and documented by any of the following parameters
• Two consecutively rising PSA values, above the baseline, at a minimum of 1-week intervals; the minimal value to enter the study is 1.0 ng/ml or greater; the reference value (#1) is the last PSA measured before increases are documented, with subsequent values obtained a minimum of 1 week apart; if the PSA at time point 3 (value #3A) is greater than that at point 2, then eligibility has been met; if the PSA is not greater than point 2 (value #3B), but value #4 is, the patient is eligible assuming that other criteria are met, if values 3A or #4 are 1 ng/mL or higher (Prostate Cancer Working Group 3)
• Appearance of one or more new lesions on bone scan
• Progressive disease by RECIST 1.1
• Must have a tumor lesion safely accessible for biopsy per the investigator's discretion; while a soft tissue metastasis is preferred for a biopsy, a bone metastasis is allowed for biopsy as long as enough cores can be obtained; a biopsied lesion cannot be used for target lesion for response assessment
• Must be agreeable to the mandatory research tumor biopsies (pre-treatment and on-treatment); tumor biopsies are mandatory at pre-treatment and at on-treatment; there is an optional biopsy at post-progression
• Must have received at least one prior line of therapy for mCRPC; a taxane chemotherapy administered for metastatic castration sensitive disease will not count, unless patient develops disease progression within 12 months from the last dose chemotherapy
• Must have a life expectancy greater than or equal to 16 weeks
• If patient is currently on prednisone or other corticosteroids for palliation, the dose must be less than or equal to 10 mg a day or its equivalent dose and it must have been started at least 4 weeks prior to cycle 1 day 1
• Patients must have measurable disease by RECIST v1.1, or evaluable disease with bone metastases demonstrated by Tc99 bone scan; patients with bone metastases only are allowed (NOTE: nodes \>= 1.5 cm (not \>= 2 cm) in the short axis are considered measurable, per The Prostate Cancer Working Group 3 \[PCWG3\])
• Toxicities of prior therapy (except alopecia) should be resolved to =\< grade 1 as per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0; patients with long-standing stable grade 2 neuropathy or others (e.g., adrenal insufficiency or hypothyroidism on stable doses of replacement therapy) may be allowed after discussion with the study principal investigator (PI)

You may not qualify if:

• Patients who have had chemotherapy, hormonal therapy (except LHRH agonist or antagonist), immunotherapy, radioisotope therapy, or RT within 21 days prior to start of the study agents
• Initiating bisphosphonate, or RANKL antibody therapy or adjusting the dose/regimen within 30 days prior to cycle 1 day 1 is prohibited; patients on a stable bisphosphonate regimen are eligible and may continue
• Patients who have received any other investigational agents within the past 28 days prior to cycle 1 day 1
• Patients with untreated brain metastases, spinal cord compression, or evidence of symptomatic brain metastases or leptomeningeal disease as noted on computed tomography (CT) or magnetic resonance imaging (MRI) scans are excluded from this clinical trial; while screening brain MRI is not required, it should be performed if clinically indicated at the discretion of the treating investigator; should patient found to have brain metastasis, treatment of brain metastasis must precede the participation in this study
• For patients with known and treated brain metastases is allowed in this study if they fulfill ALL of the following criteria:
• The lesions have remained radiologically stable for at least six weeks after completion of brain irradiation or stereotactic brain radiosurgery, and must remain stable at the time of study entry
• There is no mass effect present radiologically and no steroids requirement for symptom control for more than 4 weeks
• Patients who have received a prior inhibitor of vascular endothelial growth factor (VEGF) signaling inhibitor, or a poly adenosine diphosphate-ribose polymerase (PARP) inhibitor administered
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to cediranib or olaparib
• Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir), moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil), strong CYP3A inducers (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil); a minimum washout period of 2 weeks prior to cycle 1 day 1 is required for strong inhibitors, and at least one week for moderate inhibitors; a minimum washout period of 4 weeks prior to cycle 1 day 1 is required for CYP3A inducers; a minimum washout period of 5 weeks prior to cycle 1 day 1 is required for enzalutamide or phenobarbital; dihydropyridine calcium-channel blockers are permitted for management of hypertension
• Current use of natural herbal products or other "folk remedies"; if using previously, patients must stop using natural herbal products while participating in this study; multivitamin, calcium (Ca)/vitamin D (Vit D) and other vitamin complex supplements are allowed
• Patients with concomitant or prior invasive malignancies within the past 5 years; subjects with limited stage basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the breast, or non-muscle invasive bladder cancer, are eligible as long as they received curative intent therapy
• Uncontrolled intercurrent illness including, but not limited to, uncontrolled seizures ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Resting ECG with corrected QT (QTc) \> 470 msec on two or more time points within a 24 hour period, noted within 14 days of treatment, or family history of long QT syndrome
• History of myocardial infarction within 6 months of the randomization

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (16)

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

Location

UC San Diego Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Kim JW, McKay RR, Radke MR, Zhao S, Taplin ME, Davis NB, Monk P, Appleman LJ, Lara PN Jr, Vaishampayan UN, Zhang J, Paul AK, Bubley G, Van Allen EM, Unlu S, Huang Y, Loda M, Shapiro GI, Glazer PM, LoRusso PM, Ivy SP, Shyr Y, Swisher EM, Petrylak DP. Randomized Trial of Olaparib With or Without Cediranib for Metastatic Castration-Resistant Prostate Cancer: The Results From National Cancer Institute 9984. J Clin Oncol. 2023 Feb 1;41(4):871-880. doi: 10.1200/JCO.21.02947. Epub 2022 Oct 18.

  PMID: 36256912 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cediranib; olaparib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Joseph Kim, MD
• Organization: Yale School of Medicine: Medical Oncology

joseph.w.kim@yale.edu

(203) 200-4822

Study Officials

• Joseph W Kim

  Yale University Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 8, 2016
• First Posted: September 9, 2016
• Study Start: August 11, 2017
• Primary Completion: March 14, 2023
• Study Completion (Estimated): June 18, 2026
• Last Updated: April 13, 2026
• Results First Posted: March 30, 2025

Record last verified: 2025-12

Locations

US (16)