Clinical Study of Metronomic Oral Cyclophosphamide in Patients With Advanced Sarcomas

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by National Cancer Centre, Singapore
Sponsor:
Information provided by (Responsible Party):
Dr Richard Quek Hong Hui, National Cancer Centre, Singapore
ClinicalTrials.gov Identifier:
NCT01716689
First received: May 13, 2012
Last updated: October 25, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention Phase
Sarcoma
Drug: oral cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Clinical Study of Metronomic Oral Cyclophosphamide in Elderly and/or Pre-treated Patients With Advanced Sarcomas

Resource links provided by NLM:


Further study details as provided by National Cancer Centre, Singapore:

Primary Outcome Measures:
  • Clinical benefit as defined by the composite of complete response (CR), partial response (PR) and stable disease (SD) lasting > 12 weeks per RECIST 1.1 as a measure of disease control [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Assessment of objective response rate (ORR) [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Assessment of progression free survival [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
  • Assessment on duration of response to oral metronomic cyclophosphamide in patients who exhibit objective responses [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 28
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients with advanced sarcoma Drug: oral cyclophosphamide
50mg daily

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants must meet the following criteria on screening examination to be eligible to participate in the study:

  1. Participants must have histologically or cytologically confirmed, metastatic and/or unresectable high grade sarcoma for which standard multi-modality curative therapies do not exist or are no longer effective. Patients with low grade sarcoma need to additionally demonstrate disease progression in the last 6 months prior to study entry.
  2. Age > 21 years
  3. Prior anti-sarcoma chemotherapy

    • Participants who are 21 to 64 years of age at the time of study entry must have received at least one line of established chemotherapy, if such treatment exists; or refused such treatment, which includes either an anthracycline and/or ifosfamide. Patients whose sarcomas do not have known established therapy are eligible for this study without the requirement of a prior therapy.
    • Participants > 65 years of age at the time of study entry are eligible for this study without the requirement for prior treatment
  4. ECOG performance status 0-3 (see Annex A)
  5. Measurable disease outside of a prior irradiated area as defined by RECIST 1.1 guidelines. A lesion in a previously irradiated area is not eligible for measurable disease unless there is objective evidence of progression of the lesion prior to study enrollment
  6. No limit to number of prior chemotherapies or biologics
  7. Participants must have normal organ function as defined below:

    • Hemoglobin > 10g/dL
    • Absolute neutrophil count (ANC) > 1500/mm3
    • Platelet count > 75,000/mm3
    • Total bilirubin < 1.5 times institutional upper limits or normal (ULN)
    • AST/ALT < 3 times ULN (< 5 times ULN if hepatic involvement is present)
    • Creatinine < 1.5 times ULN. If creatinine is > 1.5 times ULN, a calculated creatinine clearance time (CCT) should be performed and patient would be eligible for study if the calculated CCT is > 10 mL/min.

    [NB: Glomerular filtration rate (GFR) = [(140 - age) x weight [kg] x 1.22 ] / (serum creatinine [umol/L]. In women, multiply this result by 0.85

  8. Resolution, or return to baseline of all clinically significant toxicities related to prior therapies
  9. Patients must be suitable for oral drug administration
  10. Willingness to use effective means of birth control throughout the duration of clinical study and for at least 3 months after completion of study drug
  11. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of study drug administration
  12. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study.

  1. Patients diagnosed with gastrointestinal stromal tumor (GIST)
  2. Participants who have had systemic anti-cancer therapy within 3 weeks of study entry (8 weeks for nitrosoureas or mitomycin C)
  3. Palliative radiotherapy or major surgery within 3 weeks of study entry
  4. Concurrent use of any other anti-cancer therapies or study agents
  5. Symptomatic or uncontrolled brain or central nervous system metastases
  6. Participants may not be receiving any other concomitant investigational agents
  7. Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  8. Individuals with a history of a different malignancy, other than cervical cancer in situ, basal cell or squamous cell carcinoma of the skin, are ineligible, except if they have been disease-free for at least 5 years, and are deemed by the investigator to be at low risk for recurrence of that malignancy OR other primary malignancy is neither currently clinically significant nor requiring active intervention.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01716689

Locations
Singapore
National Cancer Centre Singapore Recruiting
Singapore, Singapore, 169610
Contact: Jocelycn GK Chung    64368000    Jocelycn.Chung.G.K@nccs.com.sg   
Principal Investigator: Richard Quek         
Sponsors and Collaborators
National Cancer Centre, Singapore
Investigators
Principal Investigator: Richard Quek National Cancer Centre, Singapore
  More Information

No publications provided

Responsible Party: Dr Richard Quek Hong Hui, Senior Consultant, National Cancer Centre, Singapore
ClinicalTrials.gov Identifier: NCT01716689     History of Changes
Other Study ID Numbers: NCC1201
Study First Received: May 13, 2012
Last Updated: October 25, 2012
Health Authority: Singapore: Health Science Authority

Additional relevant MeSH terms:
Sarcoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Cyclophosphamide
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014