IMPORTANCE Most patients with advanced-stage cancer develop functional losses that jeopardize their independence. pairment and pain-driven OBJECTIVE To determine whether collaborative telerehabilitation and pharmacological pain management improve function, lessen pain, and reduce requirements for inpatient care. DESIGN, SETTING, AND PATIENTS The Collaborative Care to Preserve Performance in Cancer (COPE) study was a 3-arm randomized clinical trial conducted at 3 academic medical centers within 1 health care system. Patient recruitment began in March 2013 and follow-up concluded in October 2016. Participants (N = 516) were low-level community or household ambulators with stage IIIC or IV solid or hematologic cancer. INTERVENTION Participants were randomly assigned to the (1) control arm, (2) telerehabilitation arm, or (3) telerehabilitation with pharmacological pain management arm. All patients underwent automated function and pain monitoring with data reporting to their care teams. Participants in arms 2 and 3 received 6 months of centralized telerehabilitation provided by a physical therapist-physician team. Those in arm 3 also received nurse-coordinated pharmacological pain management. MAIN OUTCOMES AND MEASURES Blinded assessment of function using the Activity Measure for Postacute Care computer adaptive test, pain interference and average intensity using the Brief Pain Inventory, and quality of life using the EQ-5D-3L was performed at baseline and months 3 and 6. Hospitalizations and discharges to postacute care facilities were recorded. RESULTS The study included 516 participants (257 women and 259 men; mean [SD] age, 65.6 [11.1] years), with 172 randomized to 1 of 3 arms. Compared with the control group, the telerehabilitation arm 2 had improved function (difference, 1.3; 95% Cl, 0.08-2.35; P =.03) and quality of life (difference, 0.04; 95% Cl, 0.004-0.071; P =.01), while both telerehabilitation arms 2 and 3 had reduced pain interference (arm 2,-0.4; 95% Cl,-0.78 to - 0.09; P =.01 and arm 3,-0.4; 95% CI,-0.79 to-0.10; P =.01), and average intensity (arm 2, - 0.4; 95% CI,-0.78 to-0.07; P =.02 and arm 3,-0.5; 95% CI,-0.84 to-0.11; P =.006). Telerehabilitation was associated with higher odds of home discharge in arms 2 (odds ratio [OR], 4.3; 95% CI, 1.3-14.3; P =.02) and 3 (OR, 3.8; 95% CI, 1.1-12.4; P =.03) and fewer days in the hospital in arm 2 (difference,-3.9 days; 95% CI,-2.4 to-4.6; P =.01). CONCLUSIONS AND RELEVANCE Collaborative telerehabilitation modestly improved function and pain, while decreasing hospital length of stay and the requirement for postacute care, but these outcomes were not enhanced with the addition of pharmacological pain management.