Lessons Learned from the Impact of COVID-19 on NCI-sponsored Cancer Prevention Clinical Trials: Moving Toward Participant-centric Study Designs.

The COVID-19 pandemic overloaded health care systems around the globe and brought travel restrictions and other mandates. These effects critically impacted cancer care and conduct of clinical trials, and required medical and research communities to incorporate changes and novel flexible workflows within clinical trials and regulations to improve efficiency. We report the impact of the pandemic on cancer prevention clinical trials managed by the Division of Cancer Prevention within the NCI, focusing on participant-centric, study staff-centric and regulatory elements. Learning lessons from this challenging period, the cancer prevention community has the opportunity to incorporate many of these necessitated novel approaches to future design of clinical trials, to streamline and improve clinical trial efficiency and impact.

Enrollment of adolescents and young adults onto SWOG cancer research network clinical trials: A comparative analysis by treatment site and era.

BACKGROUND: Few adolescents and young adults (AYAs, 15-39 years old) enroll onto cancer clinical trials, which hinders research otherwise having the potential to improve outcomes in this unique population. Prior studies have reported that AYAs are more likely to receive cancer care in community settings. The National Cancer Institute (NCI) has led efforts to increase trial enrollment through its network of NCI-designated cancer centers (NCICC) combined with community outreach through its Community Clinical Oncology Program (CCOP; replaced by the NCI Community Oncology Research Program in 2014). METHODS: Using AYA proportional enrollment (the proportion of total enrollments who were AYAs) as the primary outcome, we examined enrollment of AYAs onto SWOG therapeutic trials at NCICC, CCOP, and non-NCICC/non-CCOP sites from 2004 to 2013 by type of site, study period (2004-08 vs 2009-13), and patient demographics. RESULTS: Overall, AYA proportional enrollment was 10.1%. AYA proportional enrollment decreased between 2004-2008 and 2009-2013 (13.1% vs 8.5%, P < .001), and was higher at NCICCs than at CCOPs and non-NCICC/non-CCOPs (14.1% vs 8.3% and 9.2%, respectively; P < .001). AYA proportional enrollment declined significantly at all three site types. Proportional enrollment of AYAs who were Black or Hispanic was significantly higher at NCICCs compared with CCOPs or non-NCICC/non-CCOPs (11.5% vs 8.8, P = .048 and 11.5% vs 8.6%, P = .03, respectively). CONCLUSION: Not only did community sites enroll a lower proportion of AYAs onto cancer clinical trials, but AYA enrollment decreased in all study settings. Initiatives aimed at increasing AYA enrollment, particularly in the community setting with attention to minority status, are needed.

The challenges of clinical trials for adolescents and young adults with cancer.

In the United States, Europe, and Australia, and probably all countries of the world, older adolescents and young adults with cancer are under-represented in clinical trials of therapies that could improve their outcome. Simultaneously, the survival and mortality rates in these patients have mirrored the clinical trial accrual pattern, with little improvement compared with younger and older patients. This suggests that the relative lack of participation of adolescent and young adult patients in clinical trials has lessened their chances for as good an outcome as that enjoyed by patients in other age groups. Thus, increased availability of and participation in clinical trials is of paramount important if the current deficits in outcome in young adults and older adolescents are to be eliminated. Regardless of whether there is a causal relationship, the impact of low clinical trial activity on furthering our scientific knowledge and management of cancer during adolescence and early adulthood is detrimental.

Adolescents and young adults with cancer: the scope of the problem and criticality of clinical trials.

In the U.S., older adolescents and young adults with cancer have benefited less from therapeutic advances than did either younger or older patients. One factor that may explain this deficit is the relative lack of participation of patients in this age group on clinical trials of therapies that could improve their outcome. Comparisons were made of the participation of cancer patients on clinical trials in the U.S., as a function of patient age, with the change in national cancer mortality rate; and Surveillance, Epidemiology, End Results (SEER) cancer survival rate as a function of age. The participation rate in cancer treatment trials has been strikingly lower in 15-34-year-olds than in younger or older patients. The nadir has been apparent for both males and females in all of the major ethnic and racial groups. The national cancer mortality reduction and SEER survival improvement shows a similar age dependence. In the U.S., the age-dependence of cancer treatment trial participation, and of improvement in survival prolongation and cancer death rates, are correlated. Regardless of whether there is a causal relationship, the impact on the older adolescent and young adult U.S. population is substantial, adversely affecting the national cost of healthcare, the person-years of life lost, the loss of young people entering the job market, and the scientific knowledge and social implications of cancer during adolescence and early adulthood. National initiatives are underway to address these issues, with special emphasis on increasing the availability and access to clinical trials designed for older adolescents and young adults.

Risks and benefits of phase 1 oncology trials, 1991 through 2002.

BACKGROUND: Previous reviews of phase 1 oncology trials reported a rate of response to treatment of 4 to 6 percent and a toxicity-related death rate of 0.5 percent. These results may not reflect the rates in current phase 1 oncology trials. METHODS: We reviewed all nonpediatric phase 1 oncology trials sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute between 1991 and 2002. We report the rates of response to treatment, of stable disease, of grade 4 toxic events, and of treatment-related deaths. RESULTS: We analyzed 460 trials involving 11,935 participants, all of whom were assessed for toxicity and 10,402 of whom were assessed for a response to therapy. The overall response rate (i.e., for both complete and partial responses) was 10.6 percent, with considerable variation among trials. "Classic" phase 1 trials of single investigational chemotherapeutic agents represented only 20 percent of the trials and had a response rate of 4.4 percent. Studies that included at least one anticancer agent approved by the Food and Drug Administration constituted 46.3 percent of the trials and had a response rate of 17.8. An additional 34.1 percent of participants had stable disease or a less-than-partial response. The overall rate of death due to toxic events was 0.49 percent. Of 3465 participants for whom data on patient-specific grade 4 toxic events were available, 14.3 percent had had at least one episode of grade 4 toxic events. CONCLUSIONS: Overall response rates among phase 1 oncology trials are higher than previously reported, although they have not changed for classic phase 1 trials, and toxicity-related death rates have remained stable. Rates of response and toxicity vary, however, among the various types of phase 1 oncology trials.

National survival trends of young adults with sarcoma: lack of progress is associated with lack of clinical trial participation.

BACKGROUND: Young adults with cancer in the U.S. have had less improvement in survival than either younger patients or older patients. The authors attempted to determine whether similar deficits have occurred in young adults with sarcomas and, if so, then why. METHODS: In 38,144 young adults with sarcoma who were diagnosed during 1975-1998 and were followed by the National Cancer Institute's (NCI) Surveillance, Epidemiology, and End Results Program, the average annual percent change in 5-year survival was derived as a function of patient age. National sarcoma treatment trial data were obtained on 3242 patients who were entered onto NCI-sponsored trials during 1997-2002. RESULTS: 1) For patients with bone and soft-tissue sarcomas, except Kaposi sarcoma (KS), the least survival improvement occurred between age 15 years and age 45 years. For patients with KS, the pattern was reversed, with the greatest survival increase occurring among patients ages 30-44 years. 2) The lowest participation rate in NCI-sponsored sarcoma treatment trials occurred in patients ages 20-44 years. For patients with KS, the highest accrual rate occurred in patients ages 35-44 years. 3) The age-dependent survival improvement and clinical-trial accrual patterns were correlated directly (soft-tissue sarcomas, P < 0.005; bone sarcomas, P < 0.05; KS, P = 0.06), regardless of whether the accrual profile demonstrated a decline or a peak (KS) during early adulthood. CONCLUSIONS: The lack of survival prolongation in patients age 15-44 years in the U.S. with non-KS sarcomas may have been a result of their relative lack of participation in clinical trials. If this is true, then reversing the shortfall in survival among young adults with sarcomas, as was accomplished among patients with KS, should benefit from increased clinical trial availability, access, and participation.