A Phase lb/ll, Open Label, Single Arm Study With Olinvacimab and Capecitabine in mCRC Patients (OLCAP)

NCT04751955 | Withdrawn Phase 1 DMC

• 1 other identifier: OLCAP
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The aim on this study is to assess the safety and efficacy of the anti-VEGFR2 monoclonal antibody olinvacimab and the capecitabine in patients with metastatic colorectal carcinoma who failed two prior chemotherapies

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (2)

• Maximal tolerated dose (MTD)

  recommended phase ll dose (RP2D) of olinvacimab in combination with capecitabine

  Through phase 1b, up to 6 month

• Progression free survival

  Progression free survival of olinvacimab plus capecitabinel

  3 years

Secondary Outcomes (7)

• Objective response rate (ORR)

  2 years

• overall survival

  3 years

• Disease control rate (DCR)

  2 years

• Duration of response (DOR)

  2 years

• Time to response (TTR)

  2 years

Study Arms (1)

Olinvacimab plus Capecitabine

EXPERIMENTAL

A single arm study with Olinvacimab plus Capecitabine

Drug: Olinvacimab added to Capecitabine

Interventions

Olinvacimab added to Capecitabine DRUG

Olinvacimab: IV weekly administration In phase lb, 12mg/kg and 16mg/kg weekly IV will be tested. In phase ll, the RP2D in phase lb will be used. Capecitabine: fixed dose as an oral administration, 1250mg/m2 BID on day 1 to 14 followed by 7 days off

Also known as: Capecitabine

Olinvacimab plus Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase Ib: Subjects with a histologically-confirmed, advanced/recurrent colorectal cancer who have progressed on two prior standard chemotherapies Phase II: Histologically or cytologically confirmed colorectal cancer patient who had progressed on, were intolerant of, or were inappropriate for the treatment with fluoropyrimidine, oxaliplatin, irinotecan and targeted agents (If the subject received adjuvant chemotherapy after curative surgery and lymph node dissection for colorectal cancer, the adjuvant chemotherapy is considered to be the first-line palliative chemotherapy if the disease recurred during adjuvant chemotherapy or within 6 months after the completion of adjuvant chemotherapy.)
• Permit previous 2 lines of anti-VEGF blockades
• Age ≥ 19 years old of male and female
• ECOG performance status (PS) 0-1
• Adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• Platelet ≥ 75 x 109/L
• Serum creatinine ≤ ULN (upper limit of normal) x 1.5 or serum creatinine clearance \> 30 mL/min
• Total bilirubin: ≤ 2.0 × ULN, Subjects with a bile duct obstruction will be eligible if they meet the criteria after appropriate bile drainage
• Phase Ib: Alanine aminotransferase (AST) and aspartate aminotransferase (ALT) ≤ 3 x ULN (regardless of liver metastases)
• Phase II: AST and ALT ≤ 3 x ULN if liver metastases are absent, or AST and ALT ≤ 5 x ULN if liver metastases are present.
• Adequate cardiac function: QTc ≤480 msec; if QTc exceeds 480 msec, subjects can be enrolled if the average QTc value is less than 480 msec by measuring 3 times consecutively in total.
• The subject is able to swallow and retain oral medication
• Serum β-HCG test negative within 14 days before the first administration of the study treatment (women of childbearing potential only).

You may not qualify if:

• Patient has a known or suspicious hypersensitivity to fluoropyrimidines.
• Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the subject received an investigational drug from another clinical trial, the subject can be enrolled after 2 weeks of last administration and more than 5 x half-life of the investigational drug. If monoclonal antibody therapy including anti VEGF agent was given, the subject can be enrolled after four weeks after the last does.
• Patients with complete or partial dihydropyrimidine dehydrogenase deficiency.
• Serious uncontrolled intercurrent infections
• Serious intercurrent medical or psychiatric illness, including active cardiac disease
• Acute coronary syndrome within the 6 months prior to the initiation of study drug (including myocardial infarction or unstable angina, Coronary Artery Bypass Graft surgery, percutaneous coronary intervention and stenting)
• Heart failure ≥ grade 2 by New York Heart Association (NYHA) functional classification or that requires treatment
• Ejection fraction (EF) \<50% on multi-gated acquisition (MUGA) scan or echocardiography examination. MUGA scan or echocardiography is not required as a screening test if there is no current suspicious symptom and past history of heart failure.
• Persistent uncontrolled hypertension as defined by: systolic \>180 mmHg or diastolic \>100 mmHg despite medical treatment. Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening.
• Current or past history of clinically significant cardiac arrhythmia, atrial fibrillation, and/or conduction abnormality (e.g. congenital long QT syndrome, complete AV block)
• Any risk factors that prolong QTc or increase the probability of arrhythmia, including medication (e.g. heart failure, hypokalemia, congenital long QT syndrome, history of Torsades de Pointes)
• Active central nervous system (CNS) lesions (i.e., those with radiologically unstable or symptomatic brain lesions). For those who receive radiation or surgical treatment, the subject can be enrolled if the subject is maintained without steroid therapy and the evidence of CNS disease progression for more than 4 weeks. However, patients with leptomeningeal metastases are excluded.
• History of other primary cancer. Exceptions are as follows:
• Adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma), curatively treated in situ cancer of the cervix or stage I bladder cancer, completely resected thyroid cancer without distant metastasis in which all treatment has been completed (Appropriate wound healing is required prior to clinical trial enrollment)
• Other curatively treated solid tumors except for gastric cancer with no evidence of disease recurrence at least 36 months before participating in this trial

Sponsors & Collaborators

• Korean Cancer Study Group: lead

MeSH Terms

Interventions

Capecitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Soohyeon Lee, MD, PhD

  Korea Cancer Study Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 12, 2021
• Study Start: January 1, 2022
• Primary Completion: October 31, 2023
• Study Completion: August 31, 2024
• Last Updated: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share