Novel PET/CT Imaging Biomarkers of CB-839 in Combination With Panitumumab and Irinotecan in Patients With Metastatic and Refractory RAS Wildtype Colorectal Cancer

Phase 1

Completed

• Conditions: Colorectal Cancer; RAS Wild Type Colorectal Cancer; Metastatic Colorectal Cancer; Refractory Colorectal Cancer

• Registration Number: NCT03263429
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-8-23
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

Inclusion Criteria:<br><br> - Signed and dated written informed consent<br><br> - Histologically or cytologically-confirmed diagnosis of metastatic KRAS wildtype<br> colorectal cancer (CRC)<br><br> - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1<br><br> - In dose escalation, patients must have had at least one prior line of chemotherapy<br> for advanced disease or progressed within 6 months of adjuvant therapy (prior<br> chemotherapy and/or anti-EGFR therapy is permitted)<br><br> - In dose expansion, patients must have received prior anti-EGFR therapy and achieved<br> at least stable disease on at least one scan as their best response<br><br> - In dose expansion, patients must be willing to undergo a pre-treatment biopsy, and<br> four research PET imaging techniques (11C-Glutamine and 18F-FSPG), two pre-treatment<br> and two after one cycle of treatment<br><br> - In dose expansion, at least one measurable lesion as defined by Response Evaluation<br> Criteria in Solid Tumors (RECIST) 1.1 which can be followed by CT or magnetic<br> resonance imaging (MRI)<br><br> - Absolute neutrophil count (ANC) >= 1,500/uL<br><br> - Platelets >= 100,000/uL<br><br> - Serum albumin >= 3.0 g/dL<br><br> - Serum creatinine =< 2 mg/dL, or calculated creatinine clearance > 50 mL/min (per the<br> Cockcroft-Gault formula)<br><br> - Total bilirubin =< 1.5 times upper limit of normal (ULN)<br><br> - Aspartate transaminase (AST) and alanine aminotransferase (ALT) =< 5.0 x ULN<br><br> - Women of childbearing potential (WOCBP) must have a negative serum pregnancy test<br> within 14 days prior to receiving first dose of protocol-indicated treatment; and<br> additionally agree to use at least 2 methods of acceptable contraception or abstain<br> from heterosexual intercourse from the time of signing consent, and until 2 months<br> after patient's last dose of protocol-indicated treatment; WOCBP of childbearing<br> potential are defined as those not surgically sterile or not post-menopausal (i.e.<br> if a female patient has not had a bilateral tubal ligation, a bilateral<br> oophorectomy, or a complete hysterectomy; or has not been amenorrheic for 12 months<br> in the absence of an alternative medical cause, then patient will be considered a<br> female of childbearing potential); postmenopausal status in females under 55 years<br> of age should be confirmed with a serum follicle-stimulating hormone (FSH) level<br> within laboratory reference range for postmenopausal women<br><br> - Men able to father children who are sexually active with WOCBP must agree to use at<br> least 2 methods of acceptable contraception from the time of signing consent and<br> until 2 months after patient's last dose of protocol-indicated treatment; men able<br> to father children are defined as those who are not surgically sterile (i.e. patient<br> has not had a vasectomy)<br><br>Exclusion Criteria:<br><br> - Within 28 days before first dose of protocol-indicated treatment:<br><br> - Anti-cancer treatment including chemotherapy, radiation, hormonal therapy,<br> targeted therapy, immunotherapy, or biological therapy<br><br> - Major surgery requiring general anesthesia; (Note: within this time frame,<br> placement of a central line or portacath is acceptable and does not exclude)<br><br> - Receipt of an investigational agent<br><br> - Within 14 days before first dose of protocol-indicated treatment:<br><br> * Active uncontrolled infection; patients with infection under active treatment and<br> controlled with antibiotics initiated at least 14 days prior to initiation of<br> protocol-indicated treatment are not excluded (e.g. urinary tract infection<br> controlled with antibiotics)<br><br> - Dose escalation only: known grade 4 toxicity probably or definitely attributed to<br> past irinotecan treatment<br><br> - Active inflammatory bowel disease, other bowel disease causing chronic diarrhea<br> (defined as > 4 loose stools per day), or bowel obstruction<br><br> - History of interstitial pneumonitis or pulmonary fibrosis, or evidence of<br> interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan<br><br> - Unable to receive oral medication<br><br> - Central nervous system (CNS) metastasis, unless asymptomatic or previously treated<br> and stable; and no evidence of CNS progression for at least 30 days prior to<br> initiating protocol-indicated treatment; anticonvulsant and/or corticosteroid<br> therapy will be allowed if patient is on a stable or decreasing dose of such<br> treatment for at least 30 days prior to initiating protocol-indicated treatment<br><br> - Patients with known Gilbert's disease<br><br> - Patient is pregnant or breastfeeding<br><br> - Current or previous malignant disease (other than colorectal cancer) within the last<br> 5 years; with the exception of the following if considered curatively treated:<br> non-melanoma skin cancer(s), carcinoma in situ of the cervix, and ductal carcinoma<br> in situ; subjects with another active malignancy requiring concurrent anti-cancer<br> intervention are excluded; (Note the following does not exclude: effectively treated<br> malignancy that has been in remission for more than 5 years and is considered to be<br> cured AND no additional anti-cancer therapy is ongoing and required during the study<br> period)<br><br> - Known positive test for human immunodeficiency virus (HIV), acquired<br> immunodeficiency syndrome (AIDS), hepatitis A, hepatitis B, hepatitis C, or<br> cytomegalovirus (CMV)<br><br> - Known psychiatric condition, social circumstance, or other medical condition<br> reasonably judged by the patient's study physician to unacceptably increase the risk<br> of study participation; or to prohibit the understanding or rendering of informed<br> consent or anticipated compliance with scheduled visits, treatment schedule,<br> laboratory tests and other study requirements.

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Maximum Tolerated Dose (Phase I) of CB-839 in Combination With Panitumumab and Irinotecan Hydrochloride;Response Rate (Phase II);Recommended Phase 2 Dose of CB-839 in Combination With Panitumumab and Irinotecan Hydrochloride (Phase I)

Secondary Outcome Measures

Name	Time	Method
Disease Control Rate;Coefficient of Determination (R2) of Maximum Standardized Uptake Value (SUVmax) of Fluorine F 18 L-glutamate Derivative BAY94-9392 (18F-FSPG) Uptake Change With Tumor Size Change (Phase II);Plasma Exosomal Content (Phase II);Progression Free Survival (Phase II);Overall Survival