Colorectal Cancer
Conditions
Keywords
OCV-C02, Colorectal Cancer, Antigen specific cancer immunotherapeutic
Brief summary
To assess the safety and tolerability of OCV-C02 in Patients With Advanced or Relapsed Colorectal Cancer Who Are Refractory or Intolerant to Standard Chemotherapy
Detailed description
The incidence of dose limiting toxicity (DLT) will be evaluated in cohorts of six patients by starting OCV-C02 administration at dose level 1 (OCV-103 and OCV-104 at 0.3 mg each), increasing the dose to dose level 2 (at 1 mg each), level 3 (at 3 mg each), and then up to dose level 4 (at 6 mg each). Once-weekly administration will be repeated four times in each treatment cycle, and the incidence of DLT from Day 1 to Day 29 will be evaluated. At the end of Cycle 1, patients who wish to continue OCV-C02 treatment and have provided their written consent will be permitted to continue participation in the trial using the same dosing schedule for each subsequent cycle as that for Cycle 1.
Interventions
DRUGOCV-103 and OCV-104
0.3 mg of each
Sponsors
Otsuka Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients who have human leukocyte antigen (HLA)-A\*24:02 * Patients who have histologically-confirmed colorectal cancer (adenocarcinoma) * Patients with advanced or relapsed colorectal cancer who are refractory or intolerant to standard chemotherapy * Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at the time of enrollment in the trial.
Exclusion criteria
* Patients who are HIV antibody test positive * Patients with an active infection * Patients who have or are suspected to have CNS metastasis of colon cancer (such as metastatis of the brain)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Limiting Toxicity (DLT) | Day 29 | \[Definition of DLT\] Any of the following adverse events (AEs) that occurred by Day 29 of Cycle 1 and for which a causal relationship to OCV-C02 could not be ruled out: * Grade 3 or higher non-hematological toxicities (except for injection site reaction and laboratory abnormalities lasting \< 7 days without clinical symptoms) * The following hematological toxicities: Grade 4 or higher anemia, Grade 4 or higher neutropenia or lymphocytopenia lasting 7 days, Grade 3 or higher febrile neutropenia, Grade 4 or higher platelet count decreased. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Japanese version). In addition, a DLT-equivalent treatment-emergent adverse event (TEAE) was defined as a DLT occurred during the extend treatment period (at Cycle 2 and thereafter). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With CTCAE Grade 3 or Higher TEAEs | From the start of the study drug administration until the completion of the post-treatment observation (28 days after the last administration) | The severity (grade) of an AE was evaluated using the 5-point scale from Grade 1 to Grade 5 in accordance with CTCAE version 4.0 (Japanese version) , where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE. |
| Tumor Response Rate in Cycle 1 | Day 29 | Tumor response was graded in accordance with the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete Response (CR): Disappearance of all target lesions (any malignant lymph nodes selected as target lesions must have a reduction in the minor axis to \<10 mm) Partial Response (PR): At least a 30% decrease in the diameter sum of the target lesions as compared with the diameter sum at screening Progressive Disease (PD): At least a 20% increase in the diameter sum of the target lesions as compared with the smallest diameter sum recorded after the start of treatment, and at least 5 mm increase in the absolute increase of at least 5 mm Stable Disease (SD): Neither tumor shrinkage equivalent to PR nor tumor enlargement equivalent to PD Not Evaluable (NE): No examination is feasible or the tumor response cannot be considered as any of CR, PR, PD, and SD |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 OCV-103 and OCV-104 (0.3 mg of each)
One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle. | 6 |
| Dose Level 2 OCV-103 and OCV-104 (1 mg of each)
One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle. | 6 |
| Dose Level 3 OCV-103 and OCV-104 (3 mg of each)
One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle. | 6 |
| Dose Level 4 OCV-103 and OCV-104 (6 mg of each)
One cycle was defined as 28 days of treatment. Each subject received subcutaneous injections on Days 1, 8, 15, and 22 of each cycle. | 6 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Clear progression of the primary disease is observed | 6 | 5 | 6 | 6 |
| Overall Study | DLT occurs | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Dose Level 1 | Dose Level 2 | Dose Level 3 | Dose Level 4 | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 5 Participants | 3 Participants | 3 Participants | 15 Participants |
| Age, Continuous | 58.8 years STANDARD_DEVIATION 9 | 54.8 years STANDARD_DEVIATION 10.2 | 65.8 years STANDARD_DEVIATION 9.8 | 63.3 years STANDARD_DEVIATION 10.1 | 60.7 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized Japanese | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Region of Enrollment Japan | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 4 Participants | 3 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 2 / 6 | 2 / 6 | 1 / 6 | 3 / 6 |
Outcome results
Primary
Dose Limiting Toxicity (DLT)
\[Definition of DLT\] Any of the following adverse events (AEs) that occurred by Day 29 of Cycle 1 and for which a causal relationship to OCV-C02 could not be ruled out: * Grade 3 or higher non-hematological toxicities (except for injection site reaction and laboratory abnormalities lasting \< 7 days without clinical symptoms) * The following hematological toxicities: Grade 4 or higher anemia, Grade 4 or higher neutropenia or lymphocytopenia lasting 7 days, Grade 3 or higher febrile neutropenia, Grade 4 or higher platelet count decreased. The severity of AEs was graded in accordance with Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Japanese version). In addition, a DLT-equivalent treatment-emergent adverse event (TEAE) was defined as a DLT occurred during the extend treatment period (at Cycle 2 and thereafter).
Time frame: Day 29
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 | Dose Limiting Toxicity (DLT) | 0 participants |
| Dose Level 2 | Dose Limiting Toxicity (DLT) | 0 participants |
| Dose Level 3 | Dose Limiting Toxicity (DLT) | 0 participants |
| Dose Level 4 | Dose Limiting Toxicity (DLT) | 0 participants |
Secondary
Number of Subjects With CTCAE Grade 3 or Higher TEAEs
The severity (grade) of an AE was evaluated using the 5-point scale from Grade 1 to Grade 5 in accordance with CTCAE version 4.0 (Japanese version) , where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences; Grade 5 = Death related to AE.
Time frame: From the start of the study drug administration until the completion of the post-treatment observation (28 days after the last administration)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Level 1 | Number of Subjects With CTCAE Grade 3 or Higher TEAEs | 3 participants |
| Dose Level 2 | Number of Subjects With CTCAE Grade 3 or Higher TEAEs | 4 participants |
| Dose Level 3 | Number of Subjects With CTCAE Grade 3 or Higher TEAEs | 1 participants |
| Dose Level 4 | Number of Subjects With CTCAE Grade 3 or Higher TEAEs | 3 participants |
Secondary
Tumor Response Rate in Cycle 1
Tumor response was graded in accordance with the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete Response (CR): Disappearance of all target lesions (any malignant lymph nodes selected as target lesions must have a reduction in the minor axis to \<10 mm) Partial Response (PR): At least a 30% decrease in the diameter sum of the target lesions as compared with the diameter sum at screening Progressive Disease (PD): At least a 20% increase in the diameter sum of the target lesions as compared with the smallest diameter sum recorded after the start of treatment, and at least 5 mm increase in the absolute increase of at least 5 mm Stable Disease (SD): Neither tumor shrinkage equivalent to PR nor tumor enlargement equivalent to PD Not Evaluable (NE): No examination is feasible or the tumor response cannot be considered as any of CR, PR, PD, and SD
Time frame: Day 29
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Level 1 | Tumor Response Rate in Cycle 1 | SD | 66.7 percentage of participants |
| Dose Level 1 | Tumor Response Rate in Cycle 1 | PD | 33.3 percentage of participants |
| Dose Level 1 | Tumor Response Rate in Cycle 1 | CR | 0 percentage of participants |
| Dose Level 1 | Tumor Response Rate in Cycle 1 | PR | 0 percentage of participants |
| Dose Level 1 | Tumor Response Rate in Cycle 1 | NE | 0 percentage of participants |
| Dose Level 2 | Tumor Response Rate in Cycle 1 | SD | 16.7 percentage of participants |
| Dose Level 2 | Tumor Response Rate in Cycle 1 | PD | 83.3 percentage of participants |
| Dose Level 2 | Tumor Response Rate in Cycle 1 | PR | 0 percentage of participants |
| Dose Level 2 | Tumor Response Rate in Cycle 1 | CR | 0 percentage of participants |
| Dose Level 2 | Tumor Response Rate in Cycle 1 | NE | 0 percentage of participants |
| Dose Level 3 | Tumor Response Rate in Cycle 1 | SD | 83.3 percentage of participants |
| Dose Level 3 | Tumor Response Rate in Cycle 1 | CR | 0 percentage of participants |
| Dose Level 3 | Tumor Response Rate in Cycle 1 | PR | 0 percentage of participants |
| Dose Level 3 | Tumor Response Rate in Cycle 1 | PD | 16.7 percentage of participants |
| Dose Level 3 | Tumor Response Rate in Cycle 1 | NE | 0 percentage of participants |
| Dose Level 4 | Tumor Response Rate in Cycle 1 | PD | 33.3 percentage of participants |
| Dose Level 4 | Tumor Response Rate in Cycle 1 | PR | 0 percentage of participants |
| Dose Level 4 | Tumor Response Rate in Cycle 1 | CR | 0 percentage of participants |
| Dose Level 4 | Tumor Response Rate in Cycle 1 | SD | 66.7 percentage of participants |
| Dose Level 4 | Tumor Response Rate in Cycle 1 | NE | 0 percentage of participants |