Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Adenocarcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Olaparib

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

Olaparib 300 mg BID q 4 weeks for up to 3 cycles. The 3rd cycle will not be given if patient is found to progress post cycle 2.

Between 22-42 days post Olaparib, patients will undergo a prostatectomy.

Olaparib Pill

22-42 days post Olaparib patients will undergo surgery

Prostatectomy

Anthony Mega, MD

This study will evaluate approximately 3 months of treatment with the drug olaparib in patients with prostate cancer. A capsule formulation of olaparib (tradename Lynparza™) is approved by the United States Food and Drug Administration (FDA) for the treatment of women with advanced BRCA-mutated ovarian cancer. Olaparib is an investigational drug in prostate cancer. A tablet formulation of olaparib is being tested in this study. It is a new formulation which is more convenient for patients than the approved capsule formulation because fewer tablets of olaparib need to be taken daily than with capsules.

The purpose of the study is to evaluate whether olaparib can reduce prostate cancer with defects in DNA repair genes when olaparib is given for approximately 3 months before surgery.

1.1 Primary Objective 1.1.1. To evaluate the Prostate Specific Antigen (PSA) response rate of olaparib prior to radical prostatectomy for patients with locally advanced prostate cancer and defects in DNA repair genes.

1.2 Secondary Objectives 1.2.1 To evaluate the PSA progression-free survival of olaparib and radical prostatectomy for patients with locally advanced prostate cancer and defects in DNA repair genes.

1.2.2 To evaluate the safety of olaparib prior to radical prostatectomy for patients with locally advanced prostate cancer

1.2.3 To evaluate the rate of defects in DNA repair genes in patients with newly diagnosed locally advanced prostate cancer.

This study is for prostate cancer, therefore male participants only, are allowed.

BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes

BrUOG 337: Olaparib Prior to Radical Prostatectomy For Patients With Locally Advanced Prostate Cancer and Defects in DNA Repair Genes

Response:Reduction of at least 50% in the prostate-specific antigen level from baseline Progression:A 25% increase in PSA from baseline

Baseline then approximately 8 weeks later and 2 weeks post Olaparib, approximately 10-14 weeks after baseline and then approximately every 6 months for 2 years in follow-up.

Rhode Island Hospital

The Miriam Hospital

AstraZeneca

Brown University

Olaparib 300 mg BID q 4 weeks for up to 3 cycles. The 3rd cycle will not be given if patient is found to progress post cycle 2.

Between 22-42 days post Olaparib, patients will undergo a prostatectomy.

Olaparib Pill: 300 mg BID

Prostatectomy: 22-42 days post Olaparib patients will undergo surgery

Treatment

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

BrUOG

Number of Participants With Prostate Specific Antigen (PSA) Response

PSA Progression-free Survival of Olaparib and Radical Prostatectomy for Patients With Locally Advanced Prostate Cancer and Defects in DNA Repair Genes.

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Rare Diseases

Lung Neoplasms

Small Cell Lung Carcinoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Small Cell Lung Cancer

Durvalumab

Tremelimumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Antineoplastic Agents, Immunological

Immunologic Factors

This Arm is a standard of care Arm. Patients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks for up to 13 doses

Patients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks for up to 4 doses and 75mg intravenously of Tremelimumab every 4 weeks for up to 4 doses

Patients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks and 300 mg orally of Olaparib twice a day

Patients will receive thoracic radiotherapy (30 Gray units total, 3 Gray units X 10 fractions), then in 2-3 weeks begin 1500 mg intravenously of Durvalumab every 4 weeks and 300 mg Tremelimumab IV x 1 (single dose)

Participants in all arms will be administered 1500 mg of Durvalumab intravenously every 4 weeks.

Participants in arm B will be administered 75 mg of Tremelimumab intravenously every 4 weeks for up to 4 doses.

Participants in arm C will be self-administer 300 mg of Olaparib orally.

Thoracic Radiotherapy will be administered at 3 Gray units X 10 fractions

Thoracic Radiotherapy

Participants in arm D will be administered 300 mg of Tremelimumab intravenously in 1 single dose

Alberto A Chiappori, MD

This is a randomized multi-arm trial evaluating the safety and efficacy of thoracic radiation therapy followed by either durvalumab as monotherapy or in combination with tremelimumab or olaparib in participants with Extensive-Stage Disease Small Cell Lung Cancer (ES-SCLC) who have completed a first-line platinum-based chemotherapy regimen and achieved ongoing complete response (CR), partial response (PR) or stable disease (SD).

Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer

Sequential Maintenance With Thoracic Radiotherapy and Durvalumab (MEDI4736) Monotherapy or Durvalumab (MEDI 4736) Combinations (Tremelimumab or Olaparib) in Patients With Extensive Stage-Small Cell Lung Cancer After First Line Platinum Based Chemotherapy

Unacceptable toxicity status at the end of 13-week safety observation period with unacceptable toxicity defined as:

* Any grade 4 immune related adverse event (irAE),
* Any ≥ grade 3 noninfectious pneumonitis,
* Any ≥ grade 3 colitis,
* Any grade 3 irAE, excluding colitis or pneumonitis, that does not downgrade to grade 2 within 7 days after onset of the event despite optimal medical management including systemic corticosteroids or does not downgrade to ≤ grade 1 or baseline within 14 days,
* Liver transaminase elevation \> 8 × Upper Limit of Normal (ULN) or total bilirubin \> 5 × ULN
* Any ≥ grade 3 non-irAE with exceptions per protocol

Progression Free Survival (PFS) defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration or death due to any cause. Patients last known to be alive are censored at date of last contact.

Progression Free Survival (PFS) is defined as the duration from date of registration to date of first documentation of progression assessed by local investigator or symptomatic deterioration (as defined above) or death due to any cause. Patients last known to be alive are censored at date of last contact.

Overall Survival (OS) will is defined as the duration from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

H. Lee Moffitt Cancer Center and Research Institute

Gland and Hormone Related Diseases

Symptoms and General Pathology

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Recurrence

Cystadenocarcinoma, Serous

Cystadenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Cystic, Mucinous, and Serous

Ovarian Cancer

Ovarian Epithelial Cancer

Adenocarcinoma of the Appendix

Cohort A: Recurrent platinum-sensitive ovarian cancer (progression greater than 6 months from last receipt of platinum-based chemotherapy), approximately 37 patients could be treated with an interim analysis after 17 subjects.

All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7.

For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water.

Cohort B: Recurrent platinum-resistant ovarian cancer (progression less than or equal to 6 months of the last receipt), approximately 37 patients could be treated with an interim analysis after 12 subjects.

All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7.

For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water.

Cohort C: PARP inhibitor (PARPi) resistant (subjects who have progressed on a PARPi), patients must be platinum-sensitive, and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 subjects could be treated.

All patients will receive the combination of AZD6738 and olaparib. Patients will be administered olaparib orally twice daily at 300 mg BD. Patients will be administered AZD6738 orally once daily at 160 mg on days 1 to 7.

For ease of administration, the AZD6738 should be administered at the same time as one of the olaparib doses and thus with one glass of water.

Cohort D Part I: Patients will be platinum sensitive/platinum resistant ovarian cancer. Patient may or may not have received prior PARPi and will be enrolled irrespective of their BRCA status. The number of subjects treated will depend on the number of dose levels explored with a minimum of 12 subjects up to 30 subjects.

All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated.

Cohort D Part II: Patients with ovarian cancer who are PARP inhibitor (PARPi) resistant (patients who have progressed on a PARPi). Patients must be platinum-sensitive and have a germline or somatic BRCA mutation or an HRD mutation. Approximately 12 patients will be treated.

All patients will receive the combination of AZD6738 and olaparib. Cohort D will take a lower dose of olaparib (100-200 mg daily for a 28-day cycle) and a higher dose of AZD6738 (160-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated.

For Cohorts A, B, and C: 300 mg twice daily by mouth which is taken continuously for 28 days, which is one cycle.

Cohort D 1-2: prescribed lower dose of olaparib (100-200mg daily for a 28-day cycle). Three to five dosing schedules will be evaluated. Dose Levels 1-3: olaparib 100 mg twice daily, Days 1-28. For Dose Levels 4-5: 100-200 mg twice daily, Days 1-28. Other dose levels may be considered and will not exceed AZD6738 160mg twice daily by mouth and olaparib 150mg twice daily by mouth.

For Cohorts A, B, and C: 160 mg orally once daily for first 7 days of every cycle (Days 1-7 of each 28-day cycle).

Cohort D 1-2: Prescribed higher dose of AZD6738 (120-320 mg daily for about 14 days). Three to five dosing schedules will be evaluated.

Dose Levels 1-3: 120-160 mg twice daily, Days 1-14, in combination with olaparib twice daily, Days 1-28. Alternatively, AZD6738 at 160 mg once daily Days 1-14 with olaparib at 100-150 mg Days 1-28 may be evaluated.

Dose Levels 4-5: Alternative dosing schedule of AZD6738 at 80-160 mg once or twice daily, weekly intermittent schedule (Days 1-5, 8-12, 15-19) in combination with olaparib 100-200 mg twice daily, Days 1-28 may be evaluated. AZD6738 at 160 mg twice daily, Days 1-7 or 240 mg once daily Days 1-14 with olaparib 100-200 mg twice daily Days 1-28 may be evaluated.

Other dose levels may be considered and will not exceed AZD6738 160mg twice daily by mouth and olaparib 150mg twice daily by mouth.

AZD6738

Diego Rodriguez

Mary Kate Jones

Stéphanie Gaillard, MD, PhD

Kim MacNeill

Joyce Liu, MD

Study Team

Fiona Simpkins, MD

Investigational agent, AZD6738 will be given in combination with Olaparib to women with recurrent ovarian cancer (platinum-sensitive or platinum-resistant).

This study will determine if using Olaparib in combination with AZD6738 is safe and tolerable and also determine the objective response rate and progression free survival of combination of AZD6738 and Olaparib in women with recurrent ovarian cancer in distinct platinum-sensitive and platinum-resistant cohorts.

Gynecology Oncology trial for ovarian cancer patients.

Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer

Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD 6738 and Olaparib in Recurrent Ovarian Cancer

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 for all cohorts.

Objective response rate (CR+PR) of the combination of AZD6738 and olaparib in women with recurrent ovarian cancer in platinum-sensitive and resistant, and PARP inhibitor resistant cohorts (e.g. Cohorts A, B, C, and D).

Clinical anti-tumor effect by standard criteria (RECIST)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
BrUOG 337: Olaparib Prior to Radical Prostatectomy For Advanced Prostate Cancer Defects in DNA Repair Genes	NCT03432897	Prostate Cancer Adenocarcinoma ...	Olaparib Pill Prostatectomy	18 Years -	Brown University
Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer	NCT03923270	Small Cell Lung... Small-cell Lung...	Durvalumab Tremelimumab Olaparib Pill Thoracic Radiot... Tremelimumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Combination ATR and PARP Inhibitor (CAPRI) Trial With AZD6738 and Olaparib in Recurrent Ovarian Cancer	NCT03462342	High Grade Sero...	Olaparib Pill AZD6738	18 Years -	University of Pennsylvania
Radiotherapy and Durvalumab/Durvalumab Combo (Tremelimumab/Olaparid) for Small Cell Lung Cancer	NCT03923270	Small Cell Lung... Small-cell Lung...	Durvalumab Tremelimumab Olaparib Pill Thoracic Radiot... Tremelimumab	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

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