Adult female patients with breast cancer. MedDRA version: 20.0 Level: PT Classification code 10006187 Term: Breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Cyclophosphamide powder for oral solution 600 mg / 20 mL
Pharmaceutical Form: Powder for oral solution
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50-18-0
Concentration unit: mg/ml
Sponsors
Intas Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must sign an ICF indicating that she understands the purpose of, and procedures required for the study as described in this protocol and is willing to participate in the study. 2. Participant must be female of weight =40 kg, aged between 18 to 55 years of age inclusive, at the time of signing the informed consent. 3. Participants with documented medical history of histologically or cytologically confirmed breast cancer. 4. Participant must have of HER2 negative, ER/PR positive or negative breast cancer [as defined by American Society for Clinical Oncology (ASCO)- College of American Pathologists (CAP) guidelines] confirmed by local laboratory performed on primary tumor and/or metastatic lesion. 5. Patients who are a. Neoadjuvant, adjuvant, recurrent, or metastatic setting AND b. To be initiated on cyclophosphamide 100 mg/m2 (rounded within 5% of the prescribed dose but always in multiples of 50 mg per day) daily for at least 14 days by oral route with established treatment regimen either as a monotherapy or as part of combination therapy as per independent clinical judgement of a treating physician based on standard medical care. OR Already receiving stable dose of cyclophosphamide 100 mg/m2 (rounded within 5% of the prescribed dose in multiples of 50 mg per day) daily for at least 14 days by oral route with established treatment regimen either as a monotherapy or as part of combination therapy as per independent clinical judgement of a treating physician based on standard medical care. 6. Documented disease progression (clinical or radiographic imaging) following most-recent anti-cancer systemic study intervention regimen before current cyclophosphamide therapy (not applicable for newly diagnosed patients/adjuvant patients). 7. An Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 at screening and baseline visit. 8. Body mass index (BMI) within the range 18.5 – 30 kg/m2 (inclusive) at screening and baseline. 9. Life expectancy of =12 weeks at screening and baseline. Patients are required to be in stable health status between the two periods of the study. 10. Patient must have recovered from acute toxicity of radiotherapy or previous cycle of chemotherapy before baseline visit. Patients if have received radiotherapy (regardless of site & dose), a gap of 28 days must be maintained between the last dose of radiotherapy and baseline visit. 11. Patient with adequate hematologic, liver and renal function at screening visit. 12. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a woman of childbearing potential (WOCBP) OR • Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency when used consistently and correctly, as described in Appendix 10.4 during the intervention period and for at least 12 months after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of at least 12 months. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. • A WOCBP must have a negative highly sensitive serum pregnancy test at screening; and urine pregnancy test before the first dose of study intervention at baseline visit. • If a urine test cannot be confirmed as negative (e.g
Exclusion criteria
Exclusion criteria: 1. History of clinically significant medical condition including but not limited to liver insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances; any severe, acute, or chronic medical, psychiatric or social condition; or laboratory abnormality that as per Investigator's opinion may either (a) not be in the best interest of the participant, (b) interfere with the informed consent process and/or with compliance with the requirements of the trial, or (c) prevent, limit, or confound the protocol-specified assessments or (d) result in the variation of absorption or metabolism of drug, i.e., ulcerative colitis, or gastrointestinal disease. 2. Known allergies, hypersensitivity, or intolerance to cyclophosphamide powder or tablet or its excipients 3. Contraindications to the use of cyclophosphamide per SmPC at screening and at baseline. • Participant with bladder/urinary toxicity of cyclophosphamide. • Participant with urinary outflow obstructions or acute urothelial toxicity from cytotoxic chemotherapy or radiation therapy. • Participant with bone marrow aplasia. • Participant with severe infection within 4 weeks prior to randomization, bacteremia, or severe pneumonia OR Received oral or IV antibiotics within 2 weeks prior to Baseline visit. Patients receiving routine antibiotic prophylaxis are eligible. 4. Had of major surgery, within 12 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study or within 30 days after the last dose of study intervention administration. 5. History of hepatitis B surface antigen or hepatitis C antibody positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening Visit. 6. History of human immunodeficiency virus antibody positive, or tests positive for HIV at Screening Visit. 7. History of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders criteria within 1 year before Screening or positive test result(s) for alcohol or drugs of abuse at Screening Visit. 8. Lymphoma, leukemia, or any malignancy within the past 5 years except for malignancy under study, basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence 9. Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. 10. QTc >470 msec or QTc >480 msec in participants with bundle branch block. The QTc is the QT interval corrected for heart rate according to Bazett’s formula. It is either machine-read or manually over-read. 11. More than one prior line of chemotherapy for locally advanced or metastatic breast cancer. Radiation therapy or endocrine therapy for metastatic disease is permitted. 12. Patients unable to ingest oral medications. 13. Known CNS disease, except for treated asymptomatic CNS metastases, provided all of the following criteria are met • Only supratentorial metastases allowed. • No evidence of interim progression or hemorrhage after completion of CNS-directed therapy. • No ongoing requirement for corticosteroi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the pharmacokinetic profile and to compare bioavailability of cyclophosphamide powder relative to cyclophosphamide tablet.;Secondary Objective: - To evaluate taste/palatability of cyclophosphamide powder - To compare the safety of cyclophosphamide powder relative to cyclophosphamide tablet.;Primary end point(s): To characterize the pharmacokinetic profile and to compare bioavailability of cyclophosphamide powder relative to cyclophosphamide tablet.;Timepoint(s) of evaluation of this end point: Following pharmacokinetic parameters will be evaluated: - Primary Pharmacokinetic Parameters: Cmax,ss and AUC0-t,ss - Secondary Pharmacokinetic Parameters: Tmax,ss, Cav,ss, Ct,ss, %Fluctuation and Cpd | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To evaluate taste/palatability of cyclophosphamide powder - To compare the safety of cyclophosphamide powder relative to cyclophosphamide tablet.;Timepoint(s) of evaluation of this end point: - Test product palatability will be evaluated using palatability evaluation scale in terms of taste, flavor and mouth feel assessment. - Frequency and/or incidence of significant clinical signs and symptoms, and laboratory abnormalities during treatment | — |
Countries
India
Contacts
Public ContactMr. Kavan Pandya
Intas Pharmaceuticals Ltd.
Outcome results
None listed