Colon Cancer, Metastatic Colorectal Cancer, Rectal Cancer
Conditions
Brief summary
This study is designed as an open-label, adaptive Simon Two-Stage study to evaluate the efficacy of CTX-009 in patients with metastatic colorectal cancer. A Simon Two-Stage adaptive design will enroll approximately 37 patients into Stage 1, and if criteria are met to move to Stage 2, an additional 47 patients will be enrolled.
Interventions
DRUGCTX-009
IV infusion administered on day 1 and 15 of every 28-day cycle
Sponsors
Compass Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Approximately 37 patients will be enrolled into Stage 1, and if criteria are met to move to Stage 2, an additional 47 patients will be enrolled, for a total of approximately 84 patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. 18 years of age or older 2. Histologically or cytologically confirmed metastatic or recurrent colorectal cancers 3. The primary tumor must have been resected \> 3 months prior to planned C1D1. 4. Patients who experienced progressive disease or relapse after receiving two or three prior lines of systemic therapy in the locally advanced or metastatic setting. Prior lines of systemic treatment must have included at least one fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab containing chemotherapy regimen (in any combination and may have been administered in the neoadjuvant setting). 1. Patients whose tumor is not right sided and RAS wild type must also have received an anti-epidermal growth factor receptor (EGFR) therapy. 2. Patients with tumors harboring mutations or other alterations for which there are available targeted therapies (e.g. BRAF V600E, HER2-positive, MSI-H/dMMR, etc.) must have also received the relevant approved targeted therapies. 3. If patient received peri-operative treatment (neoadjuvant and/or adjuvant), please consult the Sponsor Medical Monitor for review of prior treatment lines. 5. At least one lesion measurable as defined by RECIST v1.1 6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 7. Predicted life expectancy of at least 12 weeks 8. Adequate hepatic and renal function within 14 days of C1D1 as described below: 1. Total bilirubin ≤ 1.5 X upper limit of normal (ULN) 2. Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 3.0 X ULN (≤ 5x ULN in case of hepatic metastasis) 3. Estimated creatinine clearance ≥ 30 mL/min based on Cockcroft-Gault estimated creatinine clearance 4. Urine protein ≤ 1+ by spot urinalysis (or, if \> 1+ then 24 hr urine protein \<1.0 g/24 hr) 9. Female patients who are women of childbearing potential (WCBP) must have a negative pregnancy test (serum-human chorionic gonadotropin \[hCG\] or urine-hCG) at Screening within 14 days of C1D1 10. Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commit to use 2 acceptable forms of birth control (defined as the use of an intrauterine device (IUD), a barrier method with spermicide, condoms, any form of hormonal contraceptives, or abstinence) for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment 11. Signed and dated Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved Informed Consent Form (ICF) before any protocol-directed screening procedures are performed
Exclusion criteria
1. From the time point of signed informed consent, 1. Less than 4 weeks have elapsed since patients had a surgery or major procedure 2. Less than 2 weeks have elapsed from the last treatment date since patients had any radiation therapy 2. Prior to planned C1D1, 1. Less than 4 weeks have elapsed since patients had chemotherapy or targeted therapy for colorectal cancer 2. Less than 4 weeks have elapsed since patients had anticancer immunotherapy or investigational drug treatment 3. A history of the following cardiovascular diseases in past 5 years may be exclusionary, as determined by the Sponsor Medical Monitor: 1. Congestive heart failure that corresponds to Class II or a higher class under New York Heart Association (NYHA) classification or less than 50% of left ventricular ejection fraction (LVEF) 2. Uncontrolled hypertension (systolic blood pressure \[SBP\]/diastolic blood pressure \[DBP\] \> 140/90 mmHg) (e.g., patient with SBP/DBP \> 140/90 mmHg despite the best care including anti-hypertensive medications) 3. Patients with a history of hypertensive crisis or pre-existing hypertensive encephalopathy 4. Pulmonary hypertension 5. Myocardial infarction 6. Uncontrolled arrhythmia 7. Unstable angina 8. Patients with any significant vascular diseases (e.g., aortic aneurysm requiring surgery or recent peripheral artery thrombosis) within 6 months prior to the initial treatment of the investigational product 4. Symptomatic or uncontrolled central nervous system (CNS) metastasis (However, patients with asymptomatic CNS metastasis can participate provided that systemic corticosteroid treatment was discontinued at least 4 weeks prior to screening and that the patient is radiologically and neurologically stable or improving) 5. A history of the following hemorrhage-related or gastroenterological disease: 1. Active hemorrhage, hemorrhagic diathesis, coagulopathy or tumor invasion into great arteries 2. History of clinically significant and active (within 6 months) gastroenterological disease, such as peptic ulcer, gastrointestinal (GI) bleeding, GI or non-GI fistula, perforation, abdominal abscess, clinical symptoms and signs of GI obstruction, need for parenteral hydration or nutrition, or inflammatory bowel disease. 6. Patients who received antiplatelet drugs (aspirin, clopidogrel, etc.) or anticoagulant drugs (warfarin, heparin, direct thrombin inhibitors, etc.) within 2 weeks prior to C1D1, or are expected to need those drugs during the clinical study. 7. Patients requiring continuous treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids (the following cases are permitted): 1. NSAIDs: Up to 3 consecutive days' use is permitted 2. Corticosteroids: Topical use of corticosteroid, such as topical intra-articular injection, intranasal administration, eye drops, inhaler, etc., or temporary systemic corticosteroid use for treatment and prevention of patient's contrast media allergy, or adverse event, is permitted 8. Severe infection requiring systemic antibiotics, antivirus drugs, etc., or other uncontrolled acute active infectious diseases 9. Patients with evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Inactive hepatitis B carriers who tested HBsAg positive may enroll provided that the patient's liver function values are normal. Also, patients with chronic HBV infection which has been controlled by the site's treatment guideline may enroll. HCV patients showing sustained viral response or patients with immunity to HBV infection may enroll 10. Patients with other severe diseases or uncontrolled illnesses that warrant the exclusion from the study (permitted only if medically controlled) including but not limited to: 1. Pre-existing hemoptysis (≥ 1/2 teaspoon of bright red blood per episode) within 28 days prior to screening 2. Major, unhealed injury, active ulcer or untreated fracture 3. History of cerebrovascular incident (ischemic or hemorrhagic stroke), transient ischemic attack or subarachnoid hemorrhage within 6 months prior to screening 4. Moderate to severe ascites and/or pleural effusion 11. Clinically significant abnormal electrocardiography (ECG) findings or history determined as clinically significant by the Investigator 12. QT interval (Fridericia's formula) (QTcF) interval \> 450 msec at the time of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | From first dose of CTX-009 until treatment discontinuation (an average of 16 weeks) | Percentage of patients whose best overall response is assessed as complete response (CR) or partial response (PR). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | From first dose of CTX-009 until treatment discontinuation (an average of 16 weeks) | Percentage of all treated patients whose best overall response was complete response (CR), partial response (PR), or stable disease (SD) for a minimum of 6 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. |
| Duration of Response | From first date of complete or partial response to first date of disease progression or death (up to 15.4 weeks) | Time from the CT or MRI that first confirmed complete (CR) or partial response PR) to the CT or MRI that first confirmed progression of disease progression (PD). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: CR: disappearance of all target lesions; PR: \>=30% decrease in the sum of the longest diameter of target lesions; PD = 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Progression-free Survival | From first dose of CTX-009 to disease progression or death (up to 5.8 months) | Time from first dose of CTX-009 to progression of disease or death. Progression of diseases is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. |
| Overall Survival | From first dose of CTX-009 to death (up to 17.8 months) | Time from first dose of CTX-009 to death |
| Incidence of Treatment-emergent Adverse Events (TEAEs) and Changes in Clinical Abnormalities | From the first CTX-009 dose to 30 days after the last CTX-009 dose (average 20 weeks) for TEAEs, from the first CTX-009 dose to 60 days after the last CTX-009 dose (average 25 weeks) for lab tests, vital signs, and ECGs. | TEAE is defined by occurrence of an adverse event that started or worsened in severity on or after the first dose of CTX-009 through 30 days after the last dose of CTX-009. Change in clinical abnormalities is defined as an increase in abnormality grade in a laboratory result, vital sign, or ECG parameter from predose result to worst postdose result (graded according to the Common Terminology Criteria for Adverse Events v5.0 for all analytes except for brain natriuretic peptide and troponin subtypes, which are interpreted in reference to the laboratory reference range for each), a post-baseline potentially clinically significant vital sign abnormality, or a post-baseline potentially clinically significant ECG abnormality. |
Countries
United States
Contacts
STUDY_DIRECTORMinori Rosales, MD, PhD
Compass Therapeutics
Participant flow
Recruitment details
The protocol required enrolment of approximately 40 (minimum of 37) response evaluable participants. A total of 49 participants were enrolled in Stage 1, yielding 40 response evaluable participants. The study results did not meet the protocol-defined criterion for progression to Stage 2, and thus enrollment ended after Stage 1.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 17 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants |
| Age, Continuous | 58.6 years STANDARD_DEVIATION 11.54 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 34 / 49 |
| other Total, other adverse events | 47 / 49 |
| serious Total, serious adverse events | 14 / 49 |
Outcome results
None listed