Feasibility and acceptability of a nurse-led telehealth intervention (BOLSTER) to support patients with peritoneal carcinomatosis and their caregivers: A pilot randomized clinical trial.

Objective: Patients with advanced gynecologic (GYN) and gastrointestinal (GI) cancers frequently develop peritoneal carcinomatosis (PC), which limits prognosis and diminishes health-related quality of life (HRQoL). Palliative procedures may improve PC symptoms, yet patients and caregivers report feeling unprepared to manage ostomies, catheters, and other complex needs. Our objectives were to (1) assess the feasibility of an efficacy trial of a nurse-led telehealth intervention (BOLSTER) for patients with PC and their caregivers; and (2) assess BOLSTER's acceptability, potential to improve patients' HRQoL and self-efficacy, and potential impact on advance care planning (ACP).

Combined aromatase, CDK4/6 and PI3K blockade using letrozole/abemaciclib/LY3023414 in endometrial cancer.

Several lines of preclinical evidence indicate that combining PI3K and CDK4/6 inhibitors may further enhance the efficacy of hormonal therapy by overcoming and acquired resistance to PI3K and CDK4/6 blockade. We evaluated the combination of abemaciclib, letrozole and LY3023414 (an orally available, selective inhibitor of the class I PI3K isoforms and mTORC1/2) in recurrent endometrial cancer (EC). This study was terminated prematurely after 5 patients initiated protocol therapy due to discontinuation of further development of LY3023414.

Kidney function in patients with ovarian cancer treated with poly (ADP-ribose) polymerase (PARP) inhibitors.

Background: Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment of ovarian cancer; however, real-world data on kidney function among patients treated with PARPi are lacking.

Methods: We identified adults treated with olaparib or niraparib between 2015 and 2021 at a major cancer center in Boston, MA, USA. We determined the incidence of any acute kidney injury (AKI), defined as at least a 1.

Phase II Trials of Iniparib (BSI-201) in Combination with Gemcitabine and Carboplatin in Patients with Recurrent Ovarian Cancer.

Background: Iniparib (BSI-201), a novel anticancer agent thought to have poly(ADP-ribose) polymerase (PARP) inhibitory activity and synergy with both gemcitabine and carboplatin (GC) was evaluated in 2 cohorts with GC.

Methods: Parallel multicenter, single-arm, phase II studies using a Simon two-stage design. Eligible patients had a histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma and demonstration of platinum-sensitive (≥6 months [mo]) or -resistant disease (relapse 2-6 mo post-platinum).

A randomized phase II trial of bevacizumab vs. bevacizumab and erlotinib as first-line consolidation after carboplatin, paclitaxel, and bevacizumab in newly diagnosed patients with mullerian tumors.

Background: The combination of paclitaxel to platinum remains the backbone of therapy in patients with advanced Mullerian tumors. In patients with newly diagnosed Mullerian tumors, we investigated the progression-free survival benefit of bevacizumab and bevacizumab and erlotinib as consolidation therapy post-induction therapy.

Methods: Sixty patients were enrolled in a phase II trial of carboplatin, paclitaxel, and bevacizumab (induction therapy).

A Phase II, Two-Stage Study of Letrozole and Abemaciclib in Estrogen Receptor-Positive Recurrent Endometrial Cancer.

Purpose: Estrogen receptor (ER)-positive endometrial cancers (ECs) are characterized by phosphatidylinositol 3-kinase (PI3K) and receptor tyrosine kinase (RTK)/RAS/β-catenin (CTNNB1) pathway alterations in approximately 90% and 80% of cases, respectively. Extensive cross-talk between ER, PI3K, and RTK/RAS/CTNNB1 pathways leads to both ligand-dependent and ligand-independent ER transcriptional activity as well as upregulation of cyclin D1 which, in complex with cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), is a critical regulator of cell cycle progression and a key mediator of resistance to hormonal therapy. We hypothesized that the combination of the aromatase inhibitor letrozole and CDK4/6 inhibitor abemaciclib would demonstrate promising activity in this setting.

Evaluation of Treatment With Talazoparib and Avelumab in Patients With Recurrent Mismatch Repair Proficient Endometrial Cancer.

Importance: Although the activity of pembrolizumab and lenvatinib (the only US Food and Drug Administration-approved immunotherapy for mismatch repair proficient endometrial cancer [MMRP EC]) is compelling, there are no biomarkers of response and most patients do not tolerate, do not respond to, or develop resistance to this regimen, highlighting the need for additional, potentially biomarker-driven therapeutic approaches for patients with recurrent MMRP EC.

Objective: To assess the potential positive outcomes and safety of the combination of the polyadenosine diphosphate-ribose polymerase inhibitor talazoparib and the programmed cell death ligand 1 (PD-L1) inhibitor avelumab in recurrent MMRP EC.

Design, Settings, And Participants: This investigator-initiated, open-label, single-arm, 2-stage, phase 2 study nonrandomized controlled trial patients at 4 institutions in the US.

A phase I study of AZD2171 and Temsirolimus in patients with advanced gynecological malignancies.

Purpose: Temsirolimus, a mTOR inhibitor, and AZD2171, a VEGFR inhibitor, have independently shown activity in patients with gynecological malignancies. Understanding the pivotal role of the PI3K/PTEN/AKT/mTOR pathway in regulating angiogenesis, a phase I study utilizing Temsirolimus and AZD2171 was initiated to study the safety of targeting the mTOR and VEGF pathway in patients with recurrent or refractory gynecological malignancies.

Methods: Patients with advanced gynecological cancers were enrolled in this phase 1 study with Temsirolimus and AZD2171.

Sequential Phase II clinical trials evaluating CRLX101 as monotherapy and in combination with bevacizumab in recurrent ovarian cancer.

Background: Topoisomerase-1 inhibitors are an important class of cytotoxics associated with toxicity that limits their use. CRLX101 is a novel cyclodextrin-containing polymer conjugate of camptothecin (CPT) that self-assembles into nanoparticles to deliver sustained levels of active CPT into cancer cells while substantially reducing systemic exposure.

Methods: We conducted sequential phase II, open label, single arm clinical trials to evaluate CRLX101 as a single agent (n = 29) and with bevacizumab (Bev) (n = 34).

Phase II Study of the WEE1 Inhibitor Adavosertib in Recurrent Uterine Serous Carcinoma.

Purpose: Uterine serous carcinoma (USC) is a distinct histologic subtype of endometrial cancer, with molecular characteristics suggesting frequent cell-cycle dysregulation paired with a high level of oncogene-driven replication stress. Adavosertib is a potent and selective oral inhibitor of the WEE1 kinase, a key regulator of the G2/M and S phase cell-cycle checkpoints. Because cells with impaired cell-cycle regulation and high replication stress may be vulnerable to WEE1 inhibition, we conducted this study to assess the activity of adavosertib monotherapy in women with recurrent USC.

Stepping into survivorship pilot study: Harnessing mobile health and principles of behavioral economics to increase physical activity in ovarian cancer survivors.

Objective: Physical activity improves physical function, quality of life, and mental health, yet fewer than 80% of ovarian cancer survivors meet activity guidelines. This pilot intervention study aimed to increase physical activity in ovarian cancer survivors by leveraging principles of behavioral economics, gamification, and social support.

Methods: This 24-week study (12-week intervention; 12-week follow-up) enrolled women with ovarian cancer after completion of first-line treatment with a self-selected "teammate.

Using COVID-19 cycle threshold and other lab values as predictors of hospitalization need.

SARS-COV-2 (COVID-19) is a novel virus that has caused over 28 million cases worldwide and over 900,000 deaths since early 2020, rightfully being classified as a pandemic. COVID-19 is diagnosed via polymerase chain reaction testing which looks at cycle threshold (CT) values of two genes, N2 and E. This study examined CT values of COVID-positive patients at the VA hospital in Reno as well as other lab values and comorbidities to determine if any could aid clinicians in predicting the need for hospitalization and higher levels of care.

A phase Ib/II and pharmacokinetic study of EP0057 (formerly CRLX101) in combination with weekly paclitaxel in patients with recurrent or persistent epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Background: EP0057 (formerly CRLX101) is an investigational nanoparticle-drug conjugate (NDC) of a cyclodextrin-based polymer backbone plus camptothecin, a topoisomerase-1 inhibitor. Prior studies showed efficacy in recurrent or persistent, epithelial ovarian, fallopian tube or primary peritoneal cancer (EOC).

Methods: This phase Ib/2 trial assessed safety and efficacy of EP0057 Q2W plus weekly paclitaxel in patients with EOC.

Combined pembrolizumab and pegylated liposomal doxorubicin in platinum resistant ovarian cancer: A phase 2 clinical trial.

Objective: Pegylated liposomal doxorubicin (PLD) in vitro may have immunomodulatory abilities and preclinical evidence suggests it synergizes with immune checkpoint blockade. We hypothesized that combining PLD and pembrolizumab would be active in patients with platinum-resistant ovarian cancer (PROC).

Methods: This was a single-arm, multi-center phase II trial.

Phase II Study of Avelumab in Patients With Mismatch Repair Deficient and Mismatch Repair Proficient Recurrent/Persistent Endometrial Cancer.

Purpose: Despite the tissue-agnostic approval of pembrolizumab in mismatch repair deficient (MMRD) solid tumors, important unanswered questions remain about the role of immune checkpoint blockade in mismatch repair-proficient (MMRP) and -deficient endometrial cancer (EC).

Methods: This phase II study evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (1) MMRD/ (polymerase ε) cohort, as defined by immunohistochemical (IHC) loss of expression of one or more mismatch repair (MMR) proteins and/or documented mutation in the exonuclease domain of ; and (2) MMRP cohort with normal IHC expression of all MMR proteins. Coprimary end points were objective response (OR) and progression-free survival at 6 months (PFS6).

A tumor board report of an 83-year-old woman with stage IB grade 3 endometrioid endometrial adenocarcinoma.

An 83-year-old woman presented with postmenopausal bleeding ultimately leading to surgery and a final diagnosis of stage IB grade 3 endometrioid endometrial adenocarcinoma. The tumor board reviewed current literature regarding the efficacy of sentinel lymph node dissection in appropriately allocating stage in high-grade endometrial cancer. The optimal role of adjuvant treatment in this setting is unclear.

Final report on serial phase II trials of all-intraperitoneal chemotherapy with or without bevacizumab for women with newly diagnosed, optimally cytoreduced carcinoma of Müllerian origin.

Background: Intraperitoneal (IP) chemotherapy can improve outcomes for women with optimally cytoreduced epithelial ovarian cancer but toxicities are a concern. We conducted 2 phase 2 trials of an IV/IP regimen using carboplatin and paclitaxel without (Trial A) and with bevacizumab (Trial B).

Methods: Both trials consisted of carboplatin AUC 6 day 1, and paclitaxel 60 mg/m on days 1,8, 15 of a 21-day cycle; in Trial B, patients received IV bevacizumab 15 mg/kg every cycle starting cycle 2.

Utilizing Clinical Pharmacist Specialist to Manage Hepatitis C Virus Patients on Direct-Acting Antiviral Therapy.

Objectives: To evaluate outcomes of a clinical pharmacist specialist (CPS)-managed hepatitis C virus (HCV) treatment clinic (HCVTC) in treating HCV-infected veterans with direct-acting antivirals (DAAs).

Methods: We established a CPS-managed HCVTC under a collaborative practice agreement with our infectious disease physician (IDP). A total of 132 veterans were treated between November 1, 2014, and November 30, 2015.

Phase 1 and 2 study of carboplatin and pralatrexate in patients with recurrent, platinum-sensitive ovarian, fallopian tube, or primary peritoneal cancer.

Background: The objective of this phase 1 and 2 trial was to identify the appropriate dose of combined carboplatin and pralatrexate for patients with recurrent, platinum-sensitive ovarian, fallopian tube, and primary peritoneal cancer.

Methods: In phase 1, patients received carboplatin (at an area under the curve of 5) and increasing doses of pralatrexate until the maximum-tolerated dose (MTD) of pralatrexate was achieved. The primary endpoint was the response rate.

A SNaPshot of potentially personalized care: Molecular diagnostics in gynecologic cancer.

Background: Genetic abnormalities underlie the development and progression of cancer, and represent potential opportunities for personalized cancer therapy in Gyn malignancies.

Methods: We identified Gyn oncology patients at the MGH Cancer Center with tumors genotyped for a panel of mutations by SNaPshot, a CLIA approved assay, validated in lung cancer, that uses SNP genotyping in degraded DNA from FFPE tissue to identify 160 described mutations across 15 cancer genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2KI, NOTCH1, NRAS, PIK3CA, PTEN, TP53).

Results: Between 5/17/10 and 8/8/13, 249 pts consented to SNaPshot analysis.

Phase I study of combination of vorinostat, carboplatin, and gemcitabine in women with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer.

Objectives: Combining histone deacetylase inhibitors and chemotherapy is synergistic. This phase I study combined escalating vorinostat doses with constant doses of carboplatin and gemcitabine for the treatment of recurrent platinum-sensitive ovarian cancer. The objectives of this study were to determine the maximally tolerated dose of this combination; secondary objectives included preliminary response rate of this regimen and toxicity profile.

Catumaxomab for the treatment of malignant ascites in patients with chemotherapy-refractory ovarian cancer: a phase II study.

Objective: The aim of this study was to investigate the efficacy and safety of intraperitoneal catumaxomab in heavily pretreated patients with chemotherapy-refractory ovarian cancer and recurrent symptomatic malignant ascites.

Methods: The study is a single-arm open-label multicenter US phase II study. Patients received 4 three-hour intraperitoneal catumaxomab infusions (10, 20, 50, and 150 μg within 10 days).

Phase 2 trial of aromatase inhibition with letrozole in patients with uterine leiomyosarcomas expressing estrogen and/or progesterone receptors.

Background: Advanced uterine leiomyosarcoma (ULMS) is an incurable disease. A significant percentage of cases of ULMS express estrogen and/or progesterone receptors (ER and/or PR). To the authors' knowledge, the role of estrogen suppression in disease management is not known.