Alpelisib and Capecitabine in Patients With PIK3CA Mutant mCRC Patients

NCT04753203 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: K2020-2011-003
• Study Type: interventional
• Target: 65
• Locations: 1 country
• Sites: 1

Brief Summary

The investigator assesses the efficacy and safety of alpelisib and capecitabine in patients with PIK3CA mutant metastatic colorectal cancer who failed two prior standard chemotherapies.

Conditions

Metastatic Colorectal Cancer; PIK3CA Gene Mutation

Outcome Measures

Primary Outcomes (2)

• Maximal tolerable dose

  Maxiaml Tolerable Dose and Recommended Phase 2 Dose of combination Maximal tolerable dose and random phase 2 dose confirmation in Alpelisib with Capecitabine in phase 1b

  up to 6 month

• Progression Free Survival

  Progression Free Survival with RP2D dose

  up to 3 years

Secondary Outcomes (5)

• Dose limiting toxicity

  Up to 6 month

• Objective response rate

  up to 3 years

• Overall survival

  up to 4 years

• Time to response

  up to 3 years

• Duration of response

  up to 3 years

Study Arms (1)

A single arm study with Alpelisib plus Capecitabine

EXPERIMENTAL

A phase lb/ll, open label, single arm study with Alpelisib plus Capecitabine in patients with PIK3CA mutant metastatic colorectal cancer

Drug: Alpelisib plus Capecitabine combination

Interventions

Alpelisib plus Capecitabine combination DRUG

Adding Alpelisib to Capecitabine as a salvage regimen in mCRC with PIK3CA mutation

A single arm study with Alpelisib plus Capecitabine

Eligibility Criteria

• Age: 19 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has signed the Informed Consent Form (ICF) prior to any screening procedures being performed
• Age ≥ 19 years old of male and female
• At each phase of the trial, subjects who meet the following requirements in each phase will be enrolled.
• Phase Ib: Subjects with a histologically-confirmed, advanced/recurrent solid tumor who have progressed on standard therapy or whose disease does not have established standard therapy and not limited to PIK3CA mutation Phase II: Subjects with histologically confirmed, PIK3CA mutated, metastatic colorectal cancer that have progressed after treatment with two prior standard chemotherapeutic agents with targeted agents such as cetuximab, bevacizumab, aflibercept (Tissue samples of colorectal cancer patients must contain just PIK3CA gene alterations. e.g. single nucleotide variants, small indels, amplifications, structural variation etc. using targeted panel sequencing.)
• ECOG performance status 0-1
• Patient has adequate bone marrow and organ function as defined by the following laboratory values:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Hemoglobin ≥ 9.0 g/dL
• Platelet ≥ 100 x 109/L
• Serum creatinine ≤ ULN (upper limit of normal) or serum creatinine clearance \> 50 mL/min
• Total bilirubin: ≤ 1.5 × ULN Subjects with a bile duct obstruction will be eligible if they meet the criteria after appropriate bile drainage; Patients with Gilbert syndrome should also be included after confirming that the total bilirubin level is ≤ 1.5 x ULN in a follow-up screening test.
• INR ≤1.5
• Potassium within normal limits, or corrected with supplements
• Fasting Serum amylase ≤ 2 × ULN
• Fasting Serum lipase ≤ ULN

You may not qualify if:

• Patient has received previous treatment with a PI3K or AKT inhibitor. (Note prior mTOR inhibitor treatment is allowed.)
• Patient has received previous capecitabine in metastatic setting.
• Patient has a known or suspicious hypersensitivity to capecitabine or other products containing fluorouracil.
• 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 was given, the subject can be enrolled after four weeks after the last does.
• 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.
• Patient has currently documented pneumonitis/interstitial lung disease
• Patient has not recovered to ≤ grade 1 (except alopecia) from related adverse effects of any prior anticancer therapy
• Radiotherapy with a wide field (more than 30% of the bone marrow) of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
• Patient who has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has not recovered from adverse effects of such procedure.
• Patient has a clinically significant cardiac disease or impaired cardiac function, such as:
• 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 \>160 mmHg or diastolic \>100 mmHg with or without anti-hypertensive medication. 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)

Sponsors & Collaborators

• Korean Cancer Study Group: lead

Study Sites (1)

Korea University Anam Hospital

Seoul, 02841, South Korea

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Alpelisib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Soohyeon Lee, MD

  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

Model Details: A phase lb/ll, open label, single arm study

Study Record Dates

• First Submitted: February 4, 2021
• First Posted: February 15, 2021
• Study Start: February 28, 2021
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2025
• Last Updated: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)