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| ID | Type | Description | Link |
|---|---|---|---|
| 2008_501 |
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This is a four-part dose-escalation and confirmation study in participants with advanced solid tumors. Part A is for dose escalation and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of MK-4827. Part B is a prostate/ovarian cancer cohort expansion. Part C is for a cohort of participants with relapsed or refractory T-cell prolymphocytic leukemia (T-PLL) or chronic lymphocytic leukemia (CLL). Part D will be for a cohort of participants with locally advanced or metastatic colorectal carcinoma (CRC), persistent or recurrent endometrial carcinoma, locally advanced or metastatic triple negative or highly proliferative estrogen receptor positive (ER+) breast cancer, or partially platinum-sensitive epithelial ovarian cancer. The study is also designed to find out whether MK-4827 causes at least 50% inhibition of poly adenosine diphosphate ribose polymerase (PARP) enzyme activity.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A-Dose escalation and confirmation | Experimental |
| |
| Part B - Prostate/Ovarian Cancer Cohort | Experimental |
| |
| Part C - T-PLL/CLL cohort | Experimental |
| |
| Part D - CRC, endometrial, breast, and ovarian cancer cohort | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MK-4827 | Drug | MK-4827 in 10 mg and 100 mg capsules given daily in a 21 day dosing cycle (dose escalation to RP2D). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose limiting toxicities (DLTs) | Cycle 1 (21 days) | |
| Percent inhibition of peripheral blood mononuclear cell PARP enzyme activity (Part A, B, and C) | Cycle 1 (Days 1-21) |
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Inclusion criteria:
Exclusion criteria:
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39019698 | Derived | Monk BJ, Romero I, Graybill W, Churruca C, O'Malley DM, Knudsen AO, Yap OWS, Baurain JF, Rose PG, Denys H, Ghamande S, Pisano C, Fabbro M, Braicu EI, Calvert PM, Amit A, Prendergast E, Taylor A, Kheibarshekan L, Zhang ZY, Zajic S, Jewell RC, Gupta D, Gonzalez-Martin A. Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer. Clin Ther. 2024 Aug;46(8):612-621. doi: 10.1016/j.clinthera.2024.06.001. Epub 2024 Jul 16. | |
| 23810788 |
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| ID | Term |
|---|---|
| D015451 | Leukemia, Lymphocytic, Chronic, B-Cell |
| D015461 | Leukemia, Prolymphocytic, T-Cell |
| D009369 | Neoplasms |
| D010051 | Ovarian Neoplasms |
| D011471 | Prostatic Neoplasms |
| D004701 | Endocrine Gland Neoplasms |
| D010049 | Ovarian Diseases |
| D000291 | Adnexal Diseases |
| D005831 | Genital Diseases, Female |
| D005832 | Genital Diseases, Male |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D004700 | Endocrine System Diseases |
| D006058 | Gonadal Disorders |
| D005834 | Genital Neoplasms, Male |
| D011469 | Prostatic Diseases |
| ID | Term |
|---|---|
| D015448 | Leukemia, B-Cell |
| D007945 | Leukemia, Lymphoid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| C545685 | niraparib |
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| Derived |
| Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, Hylands L, Riisnaes R, Forster M, Omlin A, Kreischer N, Thway K, Gevensleben H, Sun L, Loughney J, Chatterjee M, Toniatti C, Carpenter CL, Iannone R, Kaye SB, de Bono JS, Wenham RM. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol. 2013 Aug;14(9):882-92. doi: 10.1016/S1470-2045(13)70240-7. Epub 2013 Jun 28. |
| 23524863 | Derived | Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R, Reid AH, Attard G, Chen L, Kozarewa I, Gevensleben H, Campbell J, Fenwick K, Assiotis I, Olmos D, Yap TA, Fong P, Tunariu N, Koh D, Molife LR, Kaye S, Lord CJ, Ashworth A, de Bono J. Poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol. 2013 May;24(5):1416-8. doi: 10.1093/annonc/mdt074. Epub 2013 Mar 22. No abstract available. |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D015463 | Leukemia, Prolymphocytic |
| D015458 | Leukemia, T-Cell |
| D009371 | Neoplasms by Site |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D052801 | Male Urogenital Diseases |