Neoplasms

All Conditions

Behaviors and Mental Disorders

Rare Diseases

Osteosarcoma

Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Quality of Life

Soft Tissue Sarcoma

Analgesics

Central Nervous System Depressants

All Drugs and Chemicals

Morphine

Patients who underwent surgical resection of a deep intramuscular soft tissue sarcoma of the thigh

A group of healthy age-matched individuals will be identified out of an available gait lab database to compare the gait pattern with tha of the patient group

Patients who underwent surgical resection of a bone or soft tissue sarcoma of the lower extremity

3D-motion analysis and strength assessment

Functional outcome

Quality of Life Questionnaire C-30 (QLQ-C30), Impact on Participation and Autonomy Questionnaire (IPAQ) and Musculoskeletal Tumor Society Score (MSTS)

Health related quality of life (HRQoL) assessment

Hazem Wafa

Moke Lieven

Primary bone and soft tissue sarcomas are an exceptionally rare form of cancer, collectively accounting for only 1% of all malignancies diagnosed. Sarcomas often occur in the patients' extremities and treatment typically involves limb salvage surgery with bone and/or muscle resection. These surgeries often leave the patients with disfigurements, psychological trauma, and functional disabilities. Perhaps, the most difficult and life-altering decision that patients (and their parents) with primary bone sarcomas about the knee joint have to make, involves choosing the type of surgical procedure that will provide them with the outcome that meets their functional as well as aesthetic expectations.

In literature, the quality of life for patients with osteosarcoma around the knee joint after three different surgical procedures, that is, amputation, endoprosthetic reconstruction and rotationplasty was evaluated. There was found that patients treated with rotationplasty showed significantly higher functional scores compared to the two other groups of patients. Also, researchers investigated the long-term quality of life after bone sarcoma surgery around the knee joint and found that, despite the functional disability, survivors were busy with work, study, relationships, and sometimes they have founded a family.

Most published reports in the literature on assessment of gait in the lower-extremity sarcoma survivors were focused on bone sarcoma patients after wide resection and endoprosthetic reconstruction. To the knowledge of the investigator, there has been no published studies on gait analysis after resection of soft tissue sarcomas (STS) of the lower extremity. The rare and heterogeneous aspects of STS and the paucity of knowledge of movement strategies in these patients hinder the development of effective rehabilitation protocols for recovering movement after resection of STS in the lower limb.

Primary bone and soft tissue sarcomas are an exceptionally rare form of cancer, collectively accounting for only 1% of all malignancies diagnosed. There have been dramatic improvements in the survival rate of sarcoma patients in the past 40 years owing to increasing effectiveness of chemotherapy. This, along with developments in imaging techniques, have led to earlier diagnosis and more accurate preoperative staging. It is estimated that there are nearly 50,000 survivors of bone and soft tissue sarcomas in the United States. 70% of those are younger than the age of 50 years. Whilst traditional treatment for bone tumors used to be amputation, advances in surgical techniques have made limb-salvage procedures a valid alternative method of treatment in 80-85% of patients with primary bone sarcomas.

Sarcomas often occur in the patients' extremities and treatment typically involves limb salvage surgery with bone and/or muscle resection. These surgeries often leave the patients with disfigurements, psychological trauma, and functional disabilities. Perhaps, the most difficult and life-altering decision that patients (and their parents) with primary bone sarcomas about the knee joint have to make, involves choosing the type of surgical procedure that will provide them with the outcome that meets their functional as well as aesthetic expectations. In literature, the quality of life for patients with osteosarcoma around the knee joint after three different surgical procedures, that is, amputation, endoprosthetic reconstruction and rotationplasty was evaluated. There was found that patients treated with rotationplasty showed significantly higher functional scores compared to the two other groups of patients. Also, researchers investigated the long-term quality of life after bone sarcoma surgery around the knee joint and found that, despite the functional disability, survivors were busy with work, study, relationships, and sometimes they have founded a family.

There are few reports available in the literature on the quality of life in sarcoma survivors. It was found that elderly patients, retired patients, and those who live alone need more intensive psychological care. Female patients were found to cope poorly with their disease compared to male gender. It was also found that the physical status greatly influences the overall outcome and quality of life in this group of patients. This stresses the importance of enrolment in tailored rehabilitation programs.

Most published reports in the literature on assessment of gait in the lower-extremity sarcoma survivors were focused on bone sarcoma patients after wide resection and endoprosthetic reconstruction. In literature, the gait pattern after endoprosthetic replacement around the knee joint was studied and found that, despite decreased walking velocity, stride length, and stance phase of the operated limb, these patients still have a symmetrical gait. Also in another report, an electromyographic assessment of gait after bone sarcoma surgery about the knee showed prolonged activation of rectus femoris and hamstring muscles in the affected limb compared to a control group. Other researchers found that limb-salvage patients often adopt a "stiff-legged" gait pattern. These findings are of utmost importance for the development of efficient rehabilitation programs for these patients.

To the knowledge of the investigator, there has been no published studies on gait analysis after resection of soft tissue sarcomas (STS) of the lower extremity. The rare and heterogeneous aspects of STS and the paucity of knowledge of movement strategies in these patients hinder the development of effective rehabilitation protocols for recovering movement after resection of STS in the lower limb. Researchers investigated the knee extension strength and postoperative functional outcome after quadriceps resection for soft tissue sarcoma of the thigh. They found that knee extension strength decreased when the number of resected quadriceps increased and this was associated with lower functional scores. They concluded that good functional results can be expected if at least two quadriceps muscles are preserved. However, no detailed assessment of gait in this group of patients has been published.

Assessment of the Functional Outcome and Quality of Life in Sarcoma Patients

To determine the physical and mental health for patients with extremity sarcoma

To measure cancer patients' physical, psychological and social functions

To measure health-related physical activity

Universitaire Ziekenhuizen KU Leuven

Carcinoma

Carcinoma, Squamous Cell

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

Pharmaceutical Solutions

Antineoplastic Agents

Anti-Infective Agents

Fluorouracil

Imiquimod

Antimetabolites

Immunosuppressive Agents

Immunologic Factors

Immunomodulating Agents

Adjuvants, Immunologic

Interferons

Control group will receive neither 5-fluorouracil (5FU) injection nor topical Imiquimod 5% cream. This group will receive standard of care only. Lesion will be surgical resected on day 21 of study.

5-fluorouracil (5FU) Group participants will receive a 1ml intralesional injection of 5FU 50mg/ml aqueous injectable solution. One injection will be administered weekly for 3 weeks. Injections will occur on d0, d7, and d14. Standard of care will be administered on d21 of study and lesion will be surgical resected.

5-fluorouracil (5FU) + Imiquimod 5% cream Group participants will receive intralesional 5FU as in the previous group, additionally participants will also receive three-times-weekly topical application of 5% imiquimod to the same lesion. Standard of care will be administered on d21 of study and lesion will be surgical resected.

Intralesional injections of 50mg/ml over a 3 week period.

5-fluorouracil

Topical application of 5% cream over a 3 week period.

Imiquimod 5% cream

Melissa Pugliano-Mauro, MD

Jeff Plowey, MS

Jeff Plowey, MS, MBA

Emily Dando, MD

Erin Skaros, PA-C

This clinical trial proposes to evaluate a relatively unexplored approach to treatment of squamous cell carcinoma (SCC) on the lower extremities. The strategy is to directly and specifically deliver drug to the tumor. For the proposed phase I clinical trial, the investigators will perform intralesional injections of a well characterized, potent chemotherapeutic agent 5-fluorouracil (5FU) with and without a topical application of 5% imiquimod to kill topically accessible SCC cells. The goal of the study is to evaluate the safety profile and tolerability of intralesional-5FU with and without a concomitant topical imiquimod and measure the clinical objective response rate (ORR) in treated lesions compared to untreated lesions 3 weeks after treatment.

Squamous cell carcinoma (SCC) of the lower extremity is a distinct subset of cutaneous squamous cell carcinomas which tend to occur multiply in elderly women. In contrast, the majority of cutaneous SCCs occur on the head and neck, and in men more than women. Histopathological studies of lower extremity SCCs revealed that they tend to be well differentiated and have low incidence of perineural and lymphovascular invasion. SCCs of the lower extremity are also less prone to metastasis. Surgical excision has been the mainstay in the treatment of SCC, including lower extremity SCC. However, the lower extremity, as a site, is prone poor wound healing and postoperative complications such as infections. Furthermore, a phenomenon called eruptive postoperative SCC can occur, in which cytokines released during wound healing trigger secondary tumor formation in genetically predisposed cells surrounding the original SCC. Given that lower extremity SCCs are less aggressive but more prone to surgical complications when excised, the investigators believe these types of lesions may be good candidates for non-surgical treatment.

5-fluorouracil (5FU) is a chemotherapeutic agent that has been used systemically for various malignancies, but it has also been used topically or intralesionally for a variety of dermatological conditions. But reports of its use in invasive cutaneous SCC, other than in keratoacanthomas, are very limited. The investigators are aware of 3 such reports in the literature. In the largest study to date, 6 weekly intralesional injections of 5FU-epinephrine gel were performed on 23 patients with cutaneous SCC on various body sites, 22 (96%) of whom demonstrated histologically confirmed tumor clearance. This study, however, used a proprietary gel formulation which is not widely available. There are two other case reports of successful treatment of SCC with 6-8 intralesional injections of 5FU at weekly intervals. The three published studies injected 0.6ml to 2.4ml of 5FU, per each weekly session, at concentrations of 30mg/ml to 50mg/ml.

Imiquimod is a topical immune response modulator which acts through the toll-like-receptor 7 pathway. It is FDA approved for the treatment actinic keratosis, genital warts, and superficial basal cell carcinomas. It has also been used off-label for the treatment of squamous cell carcinomas in situ and invasive cutaneous squamous cell carcinomas. A review of published studies to date found 50-88% clearance rate for squamous cell carcinomas in situ treated with daily application of topical imiquimod. There is only one study, other than case reports of treating invasive squamous cell carcinomas with topical imiquimod. In that study, 7 out of 12 (71%) invasive squamous cell carcinomas cleared with topical imiquimod 5 days per week for 12 weeks. Common reported adverse reactions are erythema, pruritus, weeping, erosions, crusting at the application site.

The aim of the proposed study is to evaluate a relatively unexplored approach to treatment of SCC on the lower extremities. The strategy is to directly and specifically deliver a drug to the tumor through an injection weekly for three weeks. For the proposed phase I clinical trial, the investigators will perform intralesional injections of a well-characterized, potent chemotherapeutic agent (5-fluorouracil) to kill topically accessible SCC cells. Importantly, 5-fluorouracil is currently in clinical use with a well-established safety profile. It is anticipated that intralesional injections of 5-fluorouracil (5FU) will enable direct and specific delivery of chemotherapy to the tumor, thereby reducing the potential for systemic toxicity. Further, intralesional injections of 5FU enable tumoral delivery of locally effective concentrations of 5FU using doses that are orders of magnitude below those used currently for the intravenous (IV) treatment of multiple malignancies.

In addition to the 5FU injections, a subset of study participants will also have their lesions treated with a topical application of 5% imiquimod, another well-characterized chemotherapeutic agent with some demonstrated efficacy in treating cutaneous squamous cell carcinomas. The investigators hope that the concomitant use of topical 5% imiquimod will work synergistically with intralesional 5FU. No study published to date has been found on the concomitant use of intralesional 5FU and topical imiquimod.

Participants will have at least 1 SCC lesion greater 1cm and less than 2 cm in largest diameter, on their lower extremities. The clinical diagnosis of SCC will be confirmed histologically by a deep shave biopsy of less than half of the lesion. The remainder of the lesion will be used for intralesional injections of 5FU or intralesional 5FU/topical imiquimod according to the following schema:

In this study, a total of 30 participants will be randomly assigned into 3 groups. Randomization will be conducted using the University of Pittsburgh Cancer Institute (UPCI) randomizer, which is maintained by the Biostatistics Facility of UPCI (https://randomize.upci.pitt.edu/randomizer/home.seam).10 participants will serve as a control group, and will receive neither 5FU injection nor topical imiquimod. In another 10 participants, intralesional injections of 50mg of 5FU in 1ml aqueous injectable solution will be administered weekly for 3 weeks. In yet another 10 participants, intralesional 5FU will be administered as in the previous group, additionally participants will also receive three-times-weekly topical application of 5% imiquimod to the same lesion. At the end of week two, a 2mm punch biopsy of the lesion will be obtained for mid-point analysis, and will be stored for tissue banking and future study. A week after the last injection (week 4), the lesion will be surgical resected in all participants including the control group, to render the patients disease free. Resection is the current standard of care for these tumors. A part of, or all of, the resected tumor and surrounding skin will be stored for tissue banking and future studies to characterize and compare the tumor microenvironment before, during, and after therapy.

All lesions will be photographed and treatment response will be evaluated 4 weeks after the first 5FU injection prior to excision.

10 participants will serve as a control group, and will receive neither 5FU injection nor topical imiquimod. 10 participants will receive one 1ml intralesional injection of 50mg/ml 5FU aqueous injectable solution every week for 3 weeks. 10 participants will receive intralesional 5FU as in the previous group, additionally they will also receive concomitant three-times-weekly topical application of 5% imiquimod to the same lesion. At the end of week two, a 2mm punch biopsy of the lesion will be obtained for mid-point analysis, and will be stored for tissue banking. A week after the last injection (week 4), the lesion will be surgical resected in all participants including the control group, to render the participants disease free. Resection is the current standard of care. A portion of the resected tumor and skin will also be stored for tissue banking, for future study.

Intralesional 5-Fluorouracil (5FU), Topical Imiquimod Treatment for SCC

Phase I, Dual Arm, Open-Label, Trial of Intralesional 5-Fluorouracil (5FU) and Intralesional 5FU Combined With Topical Imiquimod in Patients With Squamous Cell Carcinoma (SCC) of the Lower Extremities

Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices)

To assess Dose Limiting Toxicities (DLT) of intralesional-5FU and intralesional 5FU combined with topical imiquimod in subjects after 3 weeks of treatment.

Dose Limiting Toxicities (DLT) are defined as:

Higher-than grade 2 hematologic or non-hematologic toxicity that is definitely, probably, or possibly related to intralesional 5FU administration and/or topical imiquimod application. The NCI common terminology criteria for adverse events (CTCAE) version 4.0 will be used.

Based on the results of the previous studies on treating SCCs with 5FU injection or topical imiquimod, significant toxicities are not expected. Adverse reactions were limited to local site reactions such as treatment site pain, induration, erythema, edema.

If a patient has a DLT, doses will be delayed if any Grade \>2 toxicities are not resolved to Grade 1 by the time of the next dose.

Measure reduction in tumor burden to assess clinical objective response rate (ORR) in treated lesions. Response will be evaluated using modified Composite Assessment of Index Lesion Severity (CAILS) criteria by bi-dimensional measurement.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Assessment of the Functional Outcome and Quality of Life in Sarcoma Patients	NCT05051059	Soft Tissue Sar... Bone Sarcoma	Functional outc... Health related ...	18 Years - 95 Years	Universitaire Ziekenhuizen KU Leuven
Intralesional 5-Fluorouracil (5FU), Topical Imiquimod Treatment for SCC	NCT03370406	Carcinoma, Squa...	5-fluorouracil Imiquimod 5% cr...	18 Years -	University of Pittsburgh
Intralesional 5-Fluorouracil (5FU), Topical Imiquimod Treatment for SCC	NCT03370406	Carcinoma, Squa...	5-fluorouracil Imiquimod 5% cr...	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for lower extremities