Neoplasms

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Sarcoma

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Soft Tissue Sarcoma

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Cyclophosphamide

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

oral cyclophosphamide

Richard Quek

This is a single arm phase II clinical study to evaluate the efficacy and safety of metronomic oral cyclophosphamide in elderly and/or pre-treated patients with advanced sarcomas.

Eligible patients will receive continuous metronomic oral cyclophosphamide at a dose of 50mg daily. Tumor assessments will be performed at baseline and every 6 weeks thereafter to assess response and disease progression. Toxicity will be monitored throughout treatment. The study's primary end point is defined as clinical benefit rate (CBR) at 12 weeks as a measure of disease control. The study is designed to distinguish a favorable true PFR of 40% from a null rate of 20% \[Van Glabbeke et al. EJC 2002\]. With a CBR of 40%, metronomic oral cyclophosphamide at this dose and schedule in this patient population will be considered worthy of further evaluation.

Clinical Study of Metronomic Oral Cyclophosphamide in Patients With Advanced Sarcomas

Phase II Clinical Study of Metronomic Oral Cyclophosphamide in Elderly and/or Pre-treated Patients With Advanced Sarcomas

National Cancer Centre, Singapore

Cardiotonic Agents

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Lenograstim

Dexrazoxane

Razoxane

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Intravenous Doxorubicin 60 mg/m² Cycle 1 then 75 mg/m² Cycle 2 to Cycle 6 D1-D21 with granulocyte-colony stimulating factor (G-CSF) and dexrazoxane.

Cyclophosphamide per os 100 mg twice a day, 1 week on, 1 week off until 2 years, or unacceptable toxicity, disease progression, withdrawn of consent or death.

6 x 3-week cycles corresponding to a maximal duration of 18 weeks

Thibaud Valentin, M.D

Meryem Brihoum

Thibaud Valentin, MD

Olivier Mir, M.D

Most advanced or metastatic soft tissue sarcoma (STS) are unfortunately incurable, making the preservation of the patient's quality of life a major goal, along with prolonging survival.

Age is not a criterion for not providing effective treatment, but the goals of treatment change with age and must be integrated into the treatment decision. Elderly patients prioritise a life free of dependency, preservation of their cognitive functions and quality of life related to their state of health. They are therefore reluctant to receive a treatment that does little to improve life expectancy at the cost of significant functional losses.

Patients aged 65 years and older account for one third of all patients with STS. In the absence of dedicated recommendations, these elderly patients are currently receiving doxorubicin-based chemotherapy as first-line treatment (as recommended for younger patients), with a substantial risk of toxicity (especially cardiac). In this specific population, previous studies have shown that oral cyclophosphamide seems to have a promising activity, but also a very acceptable toxicity.

Thus, the GERICO study aims to compare standard doxorubicin chemotherapy with oral cyclophosphamide for the treatment of elderly patients with STS.

Co-morbidities increase in number and severity with age, competing with cancer prognosis and making prioritizing medical issues necessary. Individualization of cancer treatment by integrating a comprehensive geriatric assessment (CGA) is frequently considered as essential and mandatory for elderly cancer patients. The G8 questionnaire is able to identify patients requiring CGA, with a threshold score of ≤14/17 and with a strong 1-year prognostic value.

According to guidelines, the recommended first-line treatment of these patients relies on single agent chemotherapy with anthracyclines (including doxorubicin); however, anthracycline-based treatments have modest performance in patients with metastatic STS with a median progression-free survival of about 4 months and an overall survival of about 12 months.

Previous studies have demonstrated promising activity of oral metronomic cyclophosphamide in STS patients and its favorable safety profile.

To evaluate this promising activity we designed a phase III, randomized, open-label, multicentric study comparing daily oral cyclophosphamide versus standard 3-week intravenous injection of doxorubicin in 65 years or older patients with advanced or metastatic STS.

Comparison of Oral Cyclophosphamide vs Doxorubicin in ≥65 Years Old Advanced or Metastatic Soft Tissue Sarcoma Patients

Randomized Phase III Study of Oral Cyclophosphamide vs Doxorubicin in 65 Years or Older Patients With Advanced or Metastatic Soft Tissue Sarcoma: a UNICANCER/GERICO Multicenter Program

The progression-free survival is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

The overall survival is the length of time from randomization that patients enrolled in the study are still alive.

Best response under treatment: Best response (as per RECIST v1.1) recorded from the date of randomization until the end of treatment. Each patient will be assigned one of the following categories: complete response, partial response, stable disease, disease progression, or unevaluable for response (specify reasons, e.g. early death, malignant disease; toxicity; tumor assessment not repeated/incomplete; other). Responses will have to be confirmed at least 4 weeks after the evaluation to exclude measurement errors.

Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials.

The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease.

All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

The EORTC QLQ-ELD14, a validated HRQOL questionnaire for cancer patients aged greater than or equal to70 years, is intended to supplement the QLQ-C30.

The QLQ-ELD14 contains 14 items incorporating five scales to assess mobility, worries about others, future worries, maintaining purpose, and illness burden. In addition, two single items assess joint stiffness and family support. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale. High scores indicate poor mobility, good family support, much worry about the future, good maintenance of autonomy and purpose, and high burden of illness.

Toxicity: Adverse events will be graded according to the CTCAE v5.0.

The Geriatric Core Dataset (G-CODE) was developed by the DIalog for personALization of management in geriatric OncoloGy (DIALOG) intergroup to assess the general health status of the older patient.

The G-Code contains 10 tools incorporating seven scales to assess social environment, functional status, mobility, nutritional status, cognitive status, depressive mood, and comorbidities. The total scale range 0-62. High score indicate better condition.

Compliance to oral metronomic cyclophosphamide will be assessed based on data reported by the patients (patient diary).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Clinical Study of Metronomic Oral Cyclophosphamide in Patients With Advanced Sarcomas	NCT01716689	Sarcoma	oral cyclophosp...	21 Years -	National Cancer Centre, Singapore
Clinical Study of Metronomic Oral Cyclophosphamide in Patients With Advanced Sarcomas	NCT01716689	Sarcoma	oral cyclophosp...	21 Years -	National Cancer Centre, Singapore
Comparison of Oral Cyclophosphamide vs Doxorubicin in ≥65 Years Old Advanced or Metastatic Soft Tissue Sarcoma Patients	NCT04757337	Advanced Soft-t... Metastatic Soft...	Doxorubicin Cyclophosphamid...	65 Years -	UNICANCER

Spots Global Cancer Trial Database for oral cyclophosphamide