A Phase 1 Study of Lomustine and PCV in Japanese Patients with Glioma

JRCT ID: jRCT2051230069

Registered date:19/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Glioma
• Date of first enrollment: 08/08/2023
• Target sample size: 24
• Study type: Interventional

Intervention(s)

<cohort1>
Lomustine 130 mg/m2 orally every 6 weeks.

<cohort2>
Lomustine 110 mg/m2 orally every 6 weeks.
Procarbazine 60-75 mg/m2 orally from Day 8 to Day 21.
Vincristine is administered intravenously at 1.4 mg/m2 (up to 2 mg) on Day 8 and Day29.

Outcome(s)

Primary Outcome

<Presence or absence of DLT>
Assess the presence or absence of DLT associated with lomustine monotherapy in Cycle 1.We will also assess the presence or absence of DLT in association with procarbazine, lomustine and vincristine combination therapy in Cycle 1.

Secondary Outcome

< Occurrence and severity of adverse events>
Assess adverse events by event name, date, severity, grade, causal relationship to study drug, and outcomes.
<Overall Response Rate (ORR)>
The number of patients who received investigational treatment is the denominator, and the ratio is the ratio of the number of patients who showed CR (complete response) and PR (partial response).
< Pharmacokinetics>
Measure the plasma concentration of the drug in all registered patients and identify the pharmacokinetics of lomustine in the body. Plasma drug concentrations of lomustine and its metabolites, cis-4-OH lomustine and trans-4-OH lomustine, are measured using LC-MS/MS using a lomustine plasma concentration measurement system.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

<Cohort 1>
All of the following items shall be satisfied:
1) Glioma (WHO Grade 2-4) is diagnosed by pathological diagnosis of resection or biopsy.
2) For glioma, there is a history of chemotherapy or radiation therapy, and the tumor has recurred or progressed (recurrence)
3) Measurable lesions based on the RANO criteria.
4) The age is 18 years or older.
5) Performance status (PS) is either 0-2 according to the ECOG criterion or PS3 caused only by neurological symptoms caused by the tumor (PS must be listed in the medical record).
6) The latest test value within 21 days before registration (the same day of the week 3 weeks before the registration date is acceptable) satisfies all of the following:
(i)Neutrophil count>= 1500 /mm3
(ii)Hemoglobin>= 8.0 g/dL
(iii) Platelet count>= 10 x 104 /mm3
(iv)AST=<120 U/L
(v) ALT=<120 U/L
(vi)Serum creatinine: 1.5 mg/dL or less, or creatinine clearance 60 mL/min or more (calculated by 24-hour method or Cockcroft & Gault formula)

<Cohort 2>
All of the following items shall be satisfied:
1) Pathological diagnosis of resection or biopsy has diagnosed oligodendroglioma (WHO Grade 2-3) or astrocytoma (WHO Grade 2).
2) No history of treatment for glioma except for initial surgery or radiation therapy (this is the first time)
3) If you have a history of radiotherapy, the last day of radiation is within 90 days from 28 days before the start of study drug administration (the day after the same day 4 weeks later).
4) Measurable lesions based on RANO criteria.
5) You are at least 18 years of age.
6) Performance status (PS) is either 0-2 on the ECOG criterion or PS 3 caused only by neurological symptoms caused by the tumor (PS must be listed in the medical record).
7) The latest test value within 21 days before registration (the same day of the week 3 weeks before the registration date is acceptable) satisfies all of the following:
(i)Neutrophil count>=1500 /mm3
(ii)Hemoglobin>=8.0 g/dL
(iii) Platelet count>=10 x 104 /mm3
(iv)AST=<120 U/L
(v) ALT=<120 U/L
(vi)Serum creatinine: 1.5 mg/dL or less, or creatinine clearance 60 mL/min or more (calculated by 24-hour method or Cockcroft & Gault formula)

<Common to Cohort 1 and Cohort 2>
1) Active multiple cancers (simultaneous double cancer/multiple cancers and metachronous double cancers/multiple cancers with a disease-free period of up to 2 years. However, even if the disease-free period is less than 2 years, a history of cancer with a relative survival rate of 95% or more for 5 years, such as prostate cancer in clinical stage I, stage 0 clinical stage that has completely responded to radiation therapy, laryngeal cancer in stage I, and cancer in the following pathological stage that has been completely resected, is not included in active double cancer/multiple cancers).
Gastric cancer "adenocarcinoma (general type)": stage 0-I, colon cancer (adenocarcinoma): stage 0-I, rectal cancer (adenocarcinoma): stage 0-I, esophageal cancer (squamous cell carcinoma, adenosquamous cell carcinoma): stage 0, breast cancer (non-invasive ductal carcinoma, non-invasive lobular carcinoma): stage 0, breast cancer (invasive ductal carcinoma, invasive lobular carcinoma, Paget's disease): stage 0-IIA, endometrial cancer (endometrioid adenocarcinoma, mucinous adenocarcinoma): stage I, prostate cancer (adenocarcinoma): stage I-II, Cervical cancer (squamous cell carcinoma): stage 0, thyroid cancer (papillary carcinoma, follicular carcinoma): stage I, stage II, stage III, renal cancer (pale clear cell carcinoma, anobic cell carcinoma): stage I, other lesions equivalent to intramucosal cancer
* As a general rule, staging is in accordance with UICC-TNM 7th edition or equivalent cancer handling rules.
2) Infection requiring systemic treatment.
3) Fever of 38.0degrees centigrade or higher at axillary temperature at the time of registration.
4) If you are receiving intravenous or oral steroids for brain tumors, there is no addition or increase in steroids during the period 7 days before the brain MRI scan before the start of administration.
5) Receiving continuous systemic administration (oral or intravenous) steroids or other immunosuppressive drugs for diseases other than brain tumors.
6) Complicated by poorly controlled diabetes.
7) Unstable angina (angina pectoris that develops or has exacerbated seizures within 3 weeks before enrollment) or has a history of myocardial infarction within 6 months before enrollment.
8) Interstitial pneumonia, pulmonary fibrosis, severe emphysema, or more.
9) with a history of active tuberculosis (Mycobacterium tuberculosis, Bacillus tuberculosis).
10) Contrast-enhanced MRI using gadolinium contrast medium cannot be used.
11) Have received a live vaccine within 30 days prior to the first dose of study drug.
12) There is hypersensitivity to lomustine and additives of lomustine;
13) Not responded to nitrosourea administration in the past.
14) Celiac disease or allergy.
15) Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
16) Positive for HIV antibodies.
17) Positive HBs antigen or HCV antibody. The HBs antigen test is negative, but either the HBs antibody test or the HBc antibody test is positive and the HBV-DNA quantitation is greater than or equal to the detection sensitivity.
18) Women: Women who are pregnant, breastfeeding, women who are undergoing treatment and cannot consent to contraception until at least 6 months after treatment.
Men: Men who are not able to consent to contraception during treatment and until at least 6 months after treatment.
19) Patients with psychosis or psychiatric symptoms who are judged to have difficulty participating in the study.
20) Patients who have participated in other clinical trials or clinical trials (with interventions) or have participated in other clinical trials or clinical trials and are concerned that treatment may interfere with the interpretation of the results of this clinical trial or the judgment of the investigator.
21) In addition, the attending physician deems the patient inappropriate for this study.
The following exclusion criteria cover Cohort 2 only.
22) History of severe hypersensitivity to procarbazine and vincristine.
23) You are consuming alcohol (drinking) and cannot abstain from alcohol after registration.
24) Demyelinating Charcot-Marie-Tooth disease.

Exclude criteria

<Common to Cohort 1 and Cohort 2>
1) Active multiple cancers (simultaneous double cancer/multiple cancers and metachronous double cancers/multiple cancers with a disease-free period of up to 2 years. However, even if the disease-free period is less than 2 years, a history of cancer with a relative survival rate of 95% or more for 5 years, such as prostate cancer in clinical stage I, stage 0 clinical stage that has completely responded to radiation therapy, laryngeal cancer in stage I, and cancer in the following pathological stage that has been completely resected, is not included in active double cancer/multiple cancers).
Gastric cancer "adenocarcinoma (general type)": stage 0-I, colon cancer (adenocarcinoma): stage 0-I, rectal cancer (adenocarcinoma): stage 0-I, esophageal cancer (squamous cell carcinoma, adenosquamous cell carcinoma): stage 0, breast cancer (non-invasive ductal carcinoma, non-invasive lobular carcinoma): stage 0, breast cancer (invasive ductal carcinoma, invasive lobular carcinoma, Paget's disease): stage 0-IIA, endometrial cancer (endometrioid adenocarcinoma, mucinous adenocarcinoma): stage I, prostate cancer (adenocarcinoma): stage I-II, Cervical cancer (squamous cell carcinoma): stage 0, thyroid cancer (papillary carcinoma, follicular carcinoma): stage I, stage II, stage III, renal cancer (pale clear cell carcinoma, anobic cell carcinoma): stage I, other lesions equivalent to intramucosal cancer
* As a general rule, staging is in accordance with UICC-TNM 7th edition or equivalent cancer handling rules.
2) Infection requiring systemic treatment.
3) Fever of 38.0 degrees centigrade or higher at axillary temperature at the time of registration.
4) If you are receiving intravenous or oral steroids for brain tumors, there is no addition or increase in steroids during the period 7 days before the brain MRI scan before the start of administration.
5) Receiving continuous systemic administration (oral or intravenous) steroids or other immunosuppressive drugs for diseases other than brain tumors.
6) Complicated by poorly controlled diabetes.
7) Unstable angina (angina pectoris that develops or has exacerbated seizures within 3 weeks before enrollment) or has a history of myocardial infarction within 6 months before enrollment.
8) Interstitial pneumonia, pulmonary fibrosis, severe emphysema, or more.
9) with a history of active tuberculosis (Mycobacterium tuberculosis, Bacillus tuberculosis).
10) Contrast-enhanced MRI using gadolinium contrast medium cannot be used.
11) Have received a live vaccine within 30 days prior to the first dose of study drug.
12) There is hypersensitivity to rommustine and additives of rommustine;
13) Not responded to nitrosourea administration in the past.
14) Celiac disease or allergy.
15) Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.
16) Positive for HIV antibodies.
17) Positive HBs antigen or HCV antibody. The HBs antigen test is negative, but either the HBs antibody test or the HBc antibody test is positive and the HBV-DNA quantitation is greater than or equal to the detection sensitivity.
18) Women: Women who are pregnant, breastfeeding, women who are undergoing treatment and cannot consent to contraception until at least 6 months after treatment.
Men: Men who are not able to consent to contraception during treatment and until at least 6 months after treatment.
19) Patients with psychosis or psychiatric symptoms who are judged to have difficulty participating in the study.
20) Patients who have participated in other clinical trials or clinical trials (with interventions) or have participated in other clinical trials or clinical trials and are concerned that treatment may interfere with the interpretation of the results of this clinical trial or the judgment of the investigator.
21) In addition, the attending physician deems the patient inappropriate for this study.
The following exclusion criteria cover Cohort 2 only.
22) History of severe hypersensitivity to procarbazine and vincristine.
23) You are consuming alcohol (drinking) and cannot abstain from alcohol after registration.
24) Demyelinating Charcot-Marie-Tooth disease.

Related Information

• Primary Sponsor: ARAKAWA Yoshiki
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development,nippon medac Co., Ltd.