Colorectal CancerPhase 1NCT01304602
A Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer
A Phase 1 study testing Irinotecan and BKM120 in people with Colorectal Cancer, run by University of Kansas Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Irinotecan and BKM120
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Oct 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 44Show fewer
- 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.
- INR ≤ 2 Exclusion Criteria
- 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
- chronic treatment with steroids or another immunosuppressive agent. Note: Topical applications (eg rash), inhaled sprays (eg obstructive airways diseases), eye drops or local injections (eg intra-articular) are allowed. Patients with previously treated brain metastases, who are on stable low dose corticosteroids treatment (eg dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible.
- therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.
- any medications or substances that are inhibitors or inducers of specific CYP450 enzyme(s).
- any other study agents
- Patients who have taken herbal medications and certain fruits within 7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits.
- Patients who have received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Women who are pregnant or breast feeding; adults of reproductive potential not using an effective method of birth control.
- Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (eg age appropriate, history of vasomotor symptoms) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 20 pg/mL or have had surgical bilateral oophorectomy (with or without hysterectomy) at least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential.
- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during treatment for 8 days after stopping treatment and for additional 12 weeks after study drug discontinuation. Highly effective contraception is defined as: true abstinence: Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
- Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate). For female subjects on the study, the vasectomised male partner should be the sole partner for that patient.
- Use of a combination of any two of the following (a+b): Placement of an intrauterine device (IUD) or intrauterine system (IUS); Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository; Oral contraception, injected or implanted hormonal methods are not allowed as BKM120 potentially decreases the effectiveness of hormonal contraceptives.
- Fertile males must use condom during treatment, for 8 days after stopping treatment and for additional 12 weeks after study drug discontinuation and should not father a child in this period.
- Known diagnosis of human immunodeficiency virus (HIV) infection
- History of another malignancy within 3 years, except cured basal cell skin carcinoma or excised cervical carcinoma in situ
- Previous treatment with Irinotecan who have definite progression on Irinotecan.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Cancer Center
Kansas City, Kansas, 66160
About this study
Official title: A Phase I Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer
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.
Read the detailed description
Although survival of patients with advanced colorectal cancer has improved in the last two decades, the overwhelming majority of these patients will still succumb from this disease. It is the third most commonly diagnosed malignancy in the United States. We have witnessed significant leaps in understanding colorectal cancer carcinogenesis as well as in identification of a number of prognostic and predictive factors associated with this malignancy. With the use of combination chemotherapy and the addition of targeted agents, the median survival of patients with advanced colorectal cancer has improved from 4-6 months with supportive care to over 2 years.
Molecularly directed therapy for cancer holds promise to a more personalized approach to treating cancer. Increase understanding of tumorigenesis has resulted in the identification of promising targets of therapy for more strategic approach to treatment of this malignancy. However, even with the development of molecularly directed treatment, the therapy for advanced colorectal cancer remains to be primarily palliative in nature to majority of patients. There is definite need for a more effective therapy, agents with more acceptable toxicity profiles, and drugs that could be administered without significant demand on time and activity for individual patients receiving these drugs.
This is a phase I trial of 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. This study will attempt to estimate the Maximum Tolerated Dose of the combination of irinotecan and BKM120.
- Conditions
- Colorectal Cancer
- Being tested
- Irinotecan, BKM120
- Keywords
- colorectal cancer, BKM120, irinotecan
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IrinotecanDrug
Also called Camptostar
IV over 90 minutes on day 1 of each cycle (every 2 weeks) at the cohort assigned dose level
BKM120Drug
BKM120, oral, daily starting with cycle 1/day 2 at the cohort defined dose level
| Study group | Role | What they receive |
|---|---|---|
| Irinotecan + BKM120 | Experimental | Irinotecan + BKM120 at the assigned cohort dose level. Receives: Drug: Irinotecan; Drug: BKM120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 28 days
Secondary outcomes (7)
area under the plasma concentration versus time curve (AUC) of irinotecan
Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.
Measured: up to 25.5 hours post dose of irinotecan
Change in tumor size
Disease will be assessed at baseline and then every four cycles (8 weeks) by CT or MRI. Response will be assessed following RECIST criteria. Patients will be categorized as complete response, partial response, progressive disease, stable disease, or unknown.
Measured: baseline, and every 8 weeks
Peak Plasma Concentration (Cmax) of irinotecan
Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.
Measured: up to 25.5 hours post-dose of irinotecan
biological half-life of irinotecan
Blood samples will be collected at cycle 1/day 1 and cycle 2/day 1 to determine the AUC of irinotecan in the presence and absence of BKM120.
Measured: up to 25.5 hours post dose of irinotecan
Peak Plasma Concentration (Cmax) of BKM120
The Cmax of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.
Measured: up to 25.5 hours post-dose of irinotecan
area under the plasma concentration versus time curve (AUC) of BKM120
The AUC of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.
Measured: up to 25.5 hours post dose of irinotecan
Biological half life of BKM120
The biological half life of BKM120 will be measured at Cycle 2/Day 1 for pharmacokinetic characterization of BKM120.
Measured: up to 25.5 hours post dose of irinotecan
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionApr 2014
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joaquina Baranda, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01304602
- Sponsor's protocol ID
- 12480
- Status last verified
- Jan 2017
- First submitted
- 18 Feb 2011
- Last updated
- 6 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Irinotecan and BKM120 in Previously Treated Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT01304602
- Acronym / sponsor ID
- 12480
- Conditions
- Colorectal Cancer
- Keywords
- colorectal cancer, BKM120, irinotecan
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- Feb 2011
- Primary completion
- Apr 2014 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 25 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Although survival of patients with advanced colorectal cancer has improved in the last two decades, the overwhelming majority of these patients will still succumb from this disease. It is the third most commonly diagnosed malignancy in the United States. We have witnessed significant leaps in understanding colorectal cancer carcinogenesis as well as in identification of a number of prognostic and predictive factors associated with this malignancy. With the use of combination chemotherapy and the addition of targeted agents, the median survival of patients with advanced colorectal cancer has improved from 4-6 months with supportive care to over 2 years.
Molecularly directed therapy for cancer holds promise to a more personalized approach to treating cancer. Increase understanding of tumorigenesis has resulted in the identification of promising targets of therapy for more strategic approach to treatment of this malignancy. However, even with the development of molecularly directed treatment, the therapy for advanced colorectal cancer remains to be primarily palliative in nature to majority of patients. There is definite need for a more effective therapy, agents with more acceptable toxicity profiles, and drugs that could be administered without significant demand on time and activity for individual patients receiving these drugs.
This is a phase I trial of 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. This study will attempt to estimate the Maximum Tolerated Dose of the combination of irinotecan and BKM120.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Irinotecan + BKM120 | Experimental | Drug: Irinotecan, Drug: BKM120Irinotecan + BKM120 at the assigned cohort dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (44 listed)
- 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
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IrinotecanAlso: CamptostarIV over 90 minutes on day 1 of each cycle (every 2 weeks) at the cohort assigned dose level | Drug | Irinotecan + BKM120 |
| BKM120BKM120, oral, daily starting with cycle 1/day 2 at the cohort defined dose level | Drug | Irinotecan + BKM120 |
Primary outcome
Maximum tolerated dose
Time frame: 28 days
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).
7 secondary outcomes
area under the plasma concentration versus time curve (AUC) of irinotecan
Time frame: up to 25.5 hours post dose of irinotecan
Change in tumor size
Time frame: baseline, and every 8 weeks
Peak Plasma Concentration (Cmax) of irinotecan
Time frame: up to 25.5 hours post-dose of irinotecan
biological half-life of irinotecan
Time frame: up to 25.5 hours post dose of irinotecan
Peak Plasma Concentration (Cmax) of BKM120
Time frame: up to 25.5 hours post-dose of irinotecan
area under the plasma concentration versus time curve (AUC) of BKM120
Time frame: up to 25.5 hours post dose of irinotecan
Biological half life of BKM120
Time frame: up to 25.5 hours post dose of irinotecan
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joaquina Baranda, MD principal investigator
University of Kansas Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Irinotecan and BKM120 in people with Colorectal Cancer, run by University of Kansas Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2017.