A Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer

NCT01304602 | Completed Phase 1 DMC

• 1 other identifier: 12480
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial will use the combination of irinotecan and BKM120 in patients with advanced colorectal cancer who have failed on or have become intolerant of at least one line of therapy for advanced colorectal cancer and who are candidates for irinotecan therapy.

Conditions

Colorectal Cancer

Keywords

colorectal cancer; BKM120; irinotecan

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose

  The maximum tolerated dose will be defined as the dose level prior to the dose level in which dose-escalation was stopped based on dose-limiting toxicities (DLTs). DLTs are based on specific adverse events specified in the study protocol. DLTs will be assessed during the first two cycles of treatment (28 days total).

  28 days

Secondary Outcomes (7)

• area under the plasma concentration versus time curve (AUC) of irinotecan

  up to 25.5 hours post dose of irinotecan

• Change in tumor size

  baseline, and every 8 weeks

• Peak Plasma Concentration (Cmax) of irinotecan

  up to 25.5 hours post-dose of irinotecan

• biological half-life of irinotecan

  up to 25.5 hours post dose of irinotecan

• Peak Plasma Concentration (Cmax) of BKM120

  up to 25.5 hours post-dose of irinotecan

Study Arms (1)

Irinotecan + BKM120

EXPERIMENTAL

Irinotecan + BKM120 at the assigned cohort dose level.

Drug: Irinotecan; Drug: BKM120

Interventions

Irinotecan DRUG

IV over 90 minutes on day 1 of each cycle (every 2 weeks) at the cohort assigned dose level

Also known as: Camptostar

Irinotecan + BKM120

BKM120 DRUG

BKM120, oral, daily starting with cycle 1/day 2 at the cohort defined dose level

Irinotecan + BKM120

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed metastatic or unresectable adenocarcinoma of the colon or rectum with measurable disease (patients who have become resistant or intolerant of at least one-line of chemotherapy regimen are eligible)
• Patients who had had previous treatment with Irinotecan and who have definite progression on Irinotecan are eligible provided they are not a candidate for other therapeutic treatment options. Definitive progression is defined as progression of disease while on Irinotecan or within 4 weeks of discontinuing Irinotecan.
• ≥ 18 years old
• ECOG performance status ≤ 2 (Karnofsky \> 60%)
• ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hb \>9 g/dL
• Serum bilirubin within normal range (or \< 1.5 x IULN if liver metastases present; or total bilirubin ≤ 3.0 x IULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
• AST (SGOT) or ALT (SGPT) within normal range (or ≤ 3.0 x upper limit of normal if liver metastases present)
• adequate renal function as evidenced by creatinine ≤ 1.5 x IULN or creatinine clearance ≥ 50 mL/min/1.73 m2 for subjects with creatinine levels above institutional normal.
• serum calcium (corrected for serum albumin) within normal limits. Biphosphonate use for malignant hypercalcemia control is not allowed.
• Serum magnesium ≥ the institutional lower limit of normal (ILLN) and potassium within institutional normal limits.
• serum lipase ≤ IULN; serum amylase ≤ IULN; fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
• females of child-bearing potential must have negative serum pregnancy test within 72 hours prior to treatment. Cannot be pregnant or nursing.
• Males and females must agree to use effective contraceptive method.

You may not qualify if:

• Previous treatment with chemotherapy, biologic therapy, or wide field radiotherapy \< 4 weeks or limited field radiation for palliation \< 2 weeks prior to starting study drug; must have recovered from side effects of such therapy
• Known hypersensitivity to BKM120 or to its excipients or to irinotecan
• Untreated brain metastases. Patients with metastatic CNS tumors may participate in this trial, if the patient is \> 4 weeks from therapy completion, is clinically stable and is not receiving corticosteroid therapy
• Known polymorphism in UGTAIA or Gilbert's syndrome
• Acute or chronic liver, renal disease or pancreatitis
• Medically documented history or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, history of suicidal attempt or ideation, or homicidal ideation; ≥ CTCAE grade 3 anxiety; meets cutoff score of ≥ 10 in the PHQ-9 or cut-off of ≥ 15 in GAD-7 mood scale, respectively, or selects positive response of "1, 2, or 3" to question number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9)
• Clinically significant heart disease including: Left ventricular ejection fraction (LVEF) \<50% as determined by echocardiogram; ventricular arrhythmias except for benign premature ventricular contractions; supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication; conduction abnormality requiring a pacemaker; valvular disease with documented compromised cardiac function; symptomatic pericarditis; QTc \> 480 msec on screening ECG (using QTcF formula; angina pectoris that requires use of anti-anginal medication
• History of cardiac dysfunction including: acute myocardial infarction ≤ 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function; history of documented congestive heart failure (NYHA Class III or IV; document cardiomyopathy
• Other concurrent severe and/or uncontrolled concomitant medical conditions
• Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude pneumonitis or pulmonary infiltrates
• Clinical manifestation of diabetes mellitus or steroid-induced diabetes mellitus
• Impairment of GI function or disease that may significantly alter the absorption of BKM120; diarrhea ≥ grade 2
• Major surgery ≤ 4 weeks prior to starting study drug
• Prior treatment with a P13K inhibitor; any hematopoietic colony-stimulating growth factors ≤ 2 weeks prior to starting study drug; corticosteroids ≤ 2 weeks prior to starting study drug; chemotherapy or targeted anticancer therapy ≤4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug; small molecule therapeutics (excluding monoclonal antibodies) ≤5 effective half-lives prior to starting study drug
• Currently receiving medication that has the potential to prolong the QT interval or inducing Torsades de Pointes

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; NVP-BKM120

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Joaquina Baranda, MD

  University of Kansas Medical Center

  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: SPONSOR

Study Record Dates

• First Submitted: February 18, 2011
• First Posted: February 25, 2011
• Study Start: February 1, 2011
• Primary Completion: April 1, 2014
• Study Completion: October 1, 2015
• Last Updated: January 6, 2017

Record last verified: 2017-01

Locations

US (1)