Harvey, R. Donald

Abstract Importance The addition of agents targeting critical signal mediators of cancer cell proliferation such as cyclin-dependent kinases (CDK) potentiates the efficacy of platinum chemotherapy. Objective To determine the safety and efficacy of palbociclib combined with cisplatin (cis) or carboplatin (carbo) in advanced solid malignancies Design Enrollment on dose escalation (part I) proceeded using the Bayesian adaptive design Escalation with Overdose Control (EWOC). Setting Single institution investigator initiated trial. Participants Patients with any advanced cancer after at least one prior therapy were enrolled on dose escalation to determine recommended phase II doses (RP2D). Expansion cohorts were then opened for pancreaticobiliary tract cancers. Intervention Escalating doses of palbociclib in combination with different doses of cisplatin or carboplatin. Main Outcomes and Measures Primary endpoint was objective response rate (ORR). Secondary endpoints included safety, overall survival (OS), and progression-free survival (PFS). Results We enrolled 39 patients on dose escalation (part I) and 32 additional patients on dose expansion (part II). RP2D of palbociclib 100 mg on Day 2-22 + Cisplatin (cis) 60 mg/m2 IV on Day 1 Q4W (Arm A); and palbociclib 75 mg on Day 2-22 + Carboplatin (carbo) AUC 6 IV on Day 1 Q4W (Arm B). ORR for Part I were 12.5% (Arm A) and 25% (Arm B). Median PFS and OS for dose expansion were 2.1 and 4.9 months, respectively. For PDAC, mPFS was 1.9 months (95% CI: 1.7, 2.4), and OS was 3.7 months (95% CI: 2.7, 5.7). Most common treatment-related adverse events (TRAEs—all grade %): Arm A—neutropenia (66%), thrombocytopenia (26%), nausea, fatigue, and anemia (20% each); Arm B—neutropenia (64.7%), thrombocytopenia (53%), and anemia (29%). There were no grade 4-5 TRAEs. Conclusions and Relevance The combination of palbociclib with cisplatin or carboplatin had an acceptable safety profile and clinical responses in some treatment refractory advanced cancers. There was no objective response, but about half of PDAC patients had disease stabilization. Additional efforts are needed to exploit CDK abnormalities in these patients. Clinical trial registration number: NCT02897375

PURPOSE Oncology pharmacists (OPs) play a crucial role in cancer care, treatment, survivorship, and multidisciplinary teams (MDTs). OPs have specialized training in designing, administering, monitoring, and modifying oncology chemotherapy; managing adverse events; and evaluating clinical trials and investigational drugs. Yet, the state of OP has remained largely unknown in the clinical oncology workforce of the West African region. Therefore, this study aimed to understand who reconstitutes chemotherapy and to explain the OP educational and practice needs, challenges, and solutions in Nigeria. MATERIALS AND METHODS Using a concurrent embedded mixed method design, 35 OPs completed a questionnaire, and 12 others responded to a semistructured interview. The data were then subjected to inductive thematic and descriptive analyses. RESULTS The findings showed that 54% of the OPs were responsible for chemotherapy reconstitution, and only 60% of the oncology centers had a biosafety cabinet. 91% of OPs were practicing; however, only 54% were trained in OP, and none of the OPs were board-certified. Most of the OPs spent time weekly on reconstitution, administrative duties, teaching, and training; only 3% spent on oncology clinical trials and conferences and 8% on noninterventional research. We identified four themes: (1) Some OPs are not reconstituting chemotherapy: A Call for MDT, (2) For OP, No Training is Enough, (3) Board Certification will give OPs Recognition, and (4) Introduction of OP Course in Universities. CONCLUSION To improve patient treatment outcomes, training on chemotherapy reconstitution should be prioritized, integration of OPs into MDTs, and the safe handling of chemotherapy in centers should be mandated in the region. The West African Postgraduate College of Pharmacists should be supported in expanding its curriculum and introducing OP fellowships.

e21021 Background: West Africa, especially Nigeria, faces a disproportionate burden of cancer incidence and mortality, along with disparities in cancer care and management. Oncology pharmacists (OPs) play a crucial role in cancer care, treatment, and survivorship and MDTs. OPs have specialized training in designing, administering, monitoring, and modifying oncology chemotherapy, managing adverse events, and evaluating clinical trials and investigational drugs. Yet the educational needs and state of OPs have remained largely unknown in the West African region. Methods: Using a concurrent embedded mixed method design, 35 oncology pharmacists (OPs) completed a questionnaire, and 12 others responded to a semi-structured interview. The data were then subjected to inductive thematic and descriptive analysis. Results: The quantitative findings showed that 54% of the OPs were responsible for chemotherapy reconstitution, and only 60% of the oncology centers had a biosafety cabinet. 91% of OPs were practicing oncology pharmacy (OP); however, only 54% were trained in OP, and none of the OPs were board-certified. Most of the OPs spent time weekly on chemotherapy reconstitution, administrative duties, teaching, and training; only 3% spent on oncology clinical trials and conferences and 8% on other research. Respondents ranked developing medication therapy management programs as the topmost priority area for better OP practices, and chemotherapy reconstitution is the area of OP that requires the most attention for improving patient treatment outcomes and survivorship. Inadequate training, lack of equipment, non-recognition of oncology pharmacy, availability of oncology medicines, and non-integration of multi-disciplinary teams (MDT) were the major challenges in OP practice in Nigeria. In the qualitative findings, four themes were identified: (i.) Some oncology pharmacists are not reconstituting chemotherapy: A Call for MDT, (ii.) For Oncology Pharmacy, No Training is Enough, (iii.) Board Certification will give Oncology Pharmacists Recognition, and (iv.) Introduction of Oncology Pharmacy Course in Universities. Conclusions: The findings suggest that oncology pharmacists should be included in MDTs and other cancer management, which is a critical step toward improving patient outcomes in the region. Our findings show that the safe handling of chemotherapy is problematic in this region. Hence, the National Institute for Cancer Research and Treatment and other West African countries should urgently institute a national and state task force to watchdog all oncology chemotherapy centers and ensure that those preparing chemotherapy to save cancer patients are also saved from carcinogens.

Strategies to bring clinical trials closer to patients gained momentum during the COVID-19 pandemic, enabling more participants to receive treatment and/or testing in their local communities. Incorporation of decentralized trial elements presents both opportunities and challenges, spanning regulatory, technical, and operational aspects. This ASCO research statement includes timely consensus-driven recommendations and a call for engagement of all research stakeholders. ASCO held multistakeholder meetings with leaders in oncology research and concluded that research-related regulatory and administrative requirements and burdens present critical barriers to decentralizing trials. One example is sponsor and contract research organization (CRO) use of US Food and Drug Administration (FDA)'s Statement of Investigator (Form 1572), which was found to exceed FDA's stated intent and used in conservative ways disproportionate to potential risks to participants and scientific integrity. As a result, research sites experience an avalanche of downstream administrative and regulatory activities that consume considerable resources. This statement recommends four key solutions to address such barriers and recalibrate regulatory and administrative expectations for decentralizing trials: (1) FDA should engage the research community in a public-private partnership to modernize standards and enable local access to trials; (2) sponsors and CROs should develop standards and protocols that accommodate flexible approaches, enable local participation, provide clarity around roles and requirements, and promote consistency; (3) research centers, networks, and sites should update policies and procedures to implement decentralized trial elements; and (4) research community should develop a streamlined, uniform mechanism to simplify regulatory data collection and documentation and use it consistently across trials. We can and must prioritize a concerted commitment to simplify and streamline regulatory requirements and practices to broaden access to and participation in cancer clinical trials.

This commentary is a call to action for a concerted commitment and effort to transform clinical trials and enable people with cancer to participate in clinical trials closer to home. Three key strategies are identified to address major barriers: confront challenges with the interpretation of US Food and Drug Administration Form 1572 requirements (Statement of Investigator); broaden acceptance of local laboratories and imaging centers; and invest in the creation of effective, sustainable partnerships between research centers and local providers.

Abstract Purpose: The safety, pharmacokinetics, and efficacy of elraglusib, a glycogen synthase kinase-3β (GSK-3β) small-molecule inhibitor, as monotherapy or combined with chemotherapy, in patients with relapsed or refractory solid tumors or hematologic malignancies was studied. Patients and Methods: Elraglusib (intravenously twice weekly in 3-week cycles) monotherapy dose escalation was followed by dose escalation with eight chemotherapy regimens (gemcitabine, doxorubicin, lomustine, carboplatin, irinotecan, gemcitabine/nab-paclitaxel, paclitaxel/carboplatin, and pemetrexed/carboplatin) in patients previously exposed to the same chemotherapy. Results: Patients received monotherapy (n = 67) or combination therapy (n = 171) elraglusib doses 1 to 15 mg/kg twice weekly. The initial recommended phase II dose (RP2D) of elraglusib was 15 mg/kg twice weekly and was defined, without dose-limiting toxicity observation, due to fluid volumes necessary for drug administration. The RP2D was subsequently reduced to 9.3 mg/kg once weekly to reduce elraglusib-associated central/peripheral vascular access catheter blockages. Other common elraglusib-related adverse events (AE) included transient visual changes and fatigue. Grade ≥3 treatment-emergent AEs occurred in 55.2% and 71.3% of patients on monotherapy and combination therapy, respectively. Part 1 monotherapy (n = 62) and part 2 combination (n = 138) patients were evaluable for response. In part 1, a patient with melanoma had a complete response, and a patient with acute T-cell leukemia/lymphoma had a partial response (PR). In part 2, seven PRs were observed, and the median progression-free survival and overall survival were 2.1 [95% confidence interval (CI), 2–2.6] and 6.9 (95% CI, 5.7–8.4) months, respectively. Conclusions: Elraglusib had a favorable toxicity profile as monotherapy and combined with chemotherapy and was associated with clinical benefit supporting further clinical evaluation in combination with chemotherapy.

Abstract BackgroundNigeria has the highest cancer burden in Africa with 124,815 cancer cases and 78,899 cancer deaths in 2020. The limited number of oncology specialists, inaccessibility of essential cancer medicines like chemotherapies, and suboptimal delivery of cancer care lead to poor treatment outcomes. Oncology pharmacy (OP) practitioners are critical oncology professionals in the multidisciplinary team (MDT) for cancer treatment globally. In Nigeria, there is a limited number of OP practitioners providing services like reconstitution of chemotherapy, clinical research, safe use of biosafety cabinets, and monitoring of adverse drug reactions. Although the interest in oncology pharmacy is increasing, the educational needs, available skill sets, and directed training in oncology pharmacy across the nation are unknown. In this study, we examined the educational needs of OP practitioners and worked with the West African College of Pharmacy West African Postgraduate College of Pharmacists (WAPCP), Oncology Pharmacy Practitioners Association of Nigeria (OPPAN), and the International Society of Oncology Pharmacy Practitioners to upgrade the oncology pharmacy practice in Nigeria. MethodA cross-sectional study with a semi-structured questionnaire was done in 2021 with 39 pharmacists working in oncology centers across Nigeria. General descriptive statistics and qualitative analysis was performed. ResultsThere is no board-certified oncology pharmacist in Nigeria. More than 50% of the general pharmacists working in oncology centers are responsible for chemotherapy reconstitution. Understanding chemotherapy reconstitution (automation of chemotherapeutic mixing, use of radiopharmaceuticals, etc), use of biosafety cabinets, knowledge of pharmacology, designing treatment protocols, data management, immunotherapy delivery, and oncology clinical trials were some of the most significant educational needs of the OP practitioners in Nigeria. OP practitioners are lacking in most cancer centers and MDTs. ConclusionThere is an urgent need for a specialty postgraduate training programme in oncology pharmacy in Nigeria. This would help increase oncology clinical trials, improve delivery of cancer medicines, quality of care, and management of toxicities. The West African Postgraduate College of Pharmacists and OPPAN need appropriate training resources to develop an oncology pharmacy curriculum, promote the specialty and collaborate with global institutions for board certifications. Citation Format: Runcie C. Chidebe, Ramatu M. Alabelewe, Darlingtina K. Esiaka, Gloria C. Okwu, Tochukwu C. Orjiakor, Nwamaka Lasebikan, Jacinta Emejulu, Adamu A. Umar, Ndifreke Okwuegbunam, Funsho David, Toyosi Adepoju, Krishna Prasad Sapkota, Candidus C. Nwakasi, Agha A. Agha, Simeon C. Aruah, Katy Graef, Richard Mshelia, Rob Duncombe, Matthew O. Nwaneri, Noel Wannang, Cindy O’Bryant, R. Donald Harvey, Peace C. Babalola, Folakemi T. Odedina. Who reconstitutes my chemotherapy? Examining the educational needs of oncology pharmacy practitioners in Nigeria [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 723.

Abstract Purpose: Romidepsin dosing recommendations for patients with malignancy and varying degrees of hepatic dysfunction was lacking at the time of regulatory approval for T-cell lymphoma. We conducted a multicenter phase I clinical trial (ETCTN-9008) via the NCI Organ Dysfunction Working Group to investigate safety, first cycle MTD, and pharmacokinetic profile of romidepsin in this setting. Patients and Methods: Patients with select advanced solid tumors or hematologic malignancies were stratified according to hepatic function. Romidepsin was administered intravenously on days 1, 8, and 15 of a 28-day cycle and escalation followed a 3 + 3 design in moderate and severe impairment cohorts. Blood samples for detailed pharmacokinetic analyses were collected after the first dose. Results: Thirty-one patients received one dose of romidepsin and were evaluable for pharmacokinetic analyses in normal (n = 12), mild (n = 8), moderate (n = 5), and severe (n = 6) cohorts. Adverse events across cohorts were similar, and dose-limiting toxicity occurred in two patients (mild and severe impairment cohorts). The MTD was not determined because the geometric mean AUC values of romidepsin in moderate (7 mg/m2) and severe (5 mg/m2) impairment cohort were 114% and 116% of the normal cohort (14 mg/m2). Conclusions: Data from the ETCTN-9008 trial led to changes in the romidepsin labeling to reflect starting dose adjustment for patients with cancer and moderate and severe hepatic impairment, with no adjustment for mild hepatic impairment.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted all aspects of clinical care, including cancer clinical trials. In March 2020, ASCO launched a survey of clinical programs represented on its Cancer Research Committee and Research Community Forum Steering Group and taskforces to learn about the types of changes and challenges that clinical trial programs were experiencing early in the pandemic. There were 32 survey respondents; 14 represented academic programs, and 18 represented community-based programs. Respondents indicated that COVID-19 is leading programs to halt or prioritize screening and/or enrollment for certain clinical trials and cease research-only visits. Most reported conducting remote patient care where possible and remote visits and monitoring with sponsors and/or contract research organizations (CROs); respondents viewed this shift positively. Numerous challenges with conducting clinical trials were reported, including enrollment and protocol adherence difficulties with decreased patient visits, staffing constraints, and limited availability of ancillary services. Interactions with sponsors and CROs about modifying trial procedures were also challenging. The changes in clinical trial procedures identified by the survey could serve as strategies for other programs attempting to maintain their clinical trial portfolios during the COVID-19 pandemic. Additionally, many of the adaptations to trials made during the pandemic provide a long-term opportunity to improve and transform the clinical trial system. Specific improvements could be expanded use of more pragmatic or streamlined trial designs, fewer clinical trial–related patient visits, and minimized sponsor and CRO visits to trial programs.

e20608 Background: The American Society of Clinical Oncology recommends that physicians (MDs) assess the treatment goals and preferences of patients (pts) with advanced stage cancer. Available data, however, shows that pts’ values are not always well prioritized when making a treatment plan. Therefore, we iteratively developed a values tool containing 16 belief domains to inform MDs during conversations with their pts about the pts’ current priorities as they plan the next step in care. The purpose of this study was to determine the feasibility of using this values tool (defined as half of the tools having at least one value checked and half of the MDs discussing at least one value) in a phase I clinic setting. Methods: We audio-taped initial MD-pt conversations about potential enrollment in a phase I clinical trial at two academic medical centers (Emory and Mayo). The pts completed the values tool by selecting the 4 most important considerations for their next stage of care and were instructed to give the completed tool to the MD. The MDs were informed through the consent process but not specifically coached on use of the tool. The recorded conversations were coded using standard qualitative methodology to determine if a value from the tool was discussed. Results: There were 23 recorded encounters. All of the completed tools had at least one value checked and 19 of 23 (83%) completed tools were delivered to the MDs by the pts, as instructed. Of those who received the tool, 12 (63%) MDs discussed one or more of the values. The average satisfaction scores on a 5-point Likert scale were 3.9, 4.0, and 4.0, respectively, for tool clarity, ease of understanding, and benefit for pts who are offered a phase 1 trial (22/23 pts completed the evaluation). Average satisfaction scores from the 19 MDs who completed evaluations were 4.2 and 4.6, respectively, for influence of the tool on their treatment recommendation and accurate reflection of pts’ desires. Conclusions: The study met the predefined feasibility threshold and provides a strong rationale for future efficacy testing, including coaching of MDs. The tool was well accepted by both MDs and pts, and failure to deliver the completed tool by the pt was identified as a potential barrier to its effectiveness.