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Metastatic Colorectal CancerPhase 1/2NCT01591421

P13Kinase Inhibitor BKM120 in Combination With Panitumumab in Metastatic/Advanced RAS-Wild Type Colorectal Cancer.

A Phase 1/2 study testing BKM120 and Panitumumab in people with Metastatic Colorectal Cancer, run by Canadian Cancer Trials Group at 3 sites in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

For the first phase of this study (phase I), the purpose will be to find the dose of a new drug, BKM120, that can safely be given in combination with standard dose panitumumab. For the second phase of this study (phase II), the purpose is to find out what effects the combination of BKM120 and panitumumab, in doses… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Colorectal Cancer
What is being tested?
BKM120 and Panitumumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
3 sitesCanada
Study dates
6 Sep 2012to 12 Nov 2019
Phase
Phase 1/2
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

  • Histologic proof of a primary colorectal cancer which is recurrent or metastatic.
  • Tumour must be confirmed to be K-Ras wild type (i.e. no K-Ras mutation found) by means of mutation analysis performed on representative samples of diagnostic tumour tissue by the standard regional or provincial laboratory and be eligible to receive standard panitumumab treatment as per local guidelines (i.e. must have failed, or have been unable to receive prior irinotecan, oxaliplatin and thymidylate synthase inhibitor therapy). Note: Archival tumour samples are acceptable for K-Ras mutation analysis.
  • In the phase I portion of the trial, patients may have measurable OR non-measurable disease. Patients whose only evidence of disease progression is tumour marker elevation are not eligible.
  • In the phase II portion of the trial, all patients must have measurable disease as defined by RECIST 1.1.
  • The criteria for defining measurable disease are as follows:
  • Chest X-ray ≥ 20 mm CT/MRI scan (with slice thickness of < 5 mm) ≥ 10 mm → longest diameter Physical exam (using calipers) ≥ 10 mm Lymph nodes by CT scan ≥ 15 mm → measured in short axis
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  • Patients must have recovered from recent surgery, chemotherapy and/or radiation therapy and significant toxicity must have recovered to ≤ grade 2. At least 4 weeks must have elapsed from major surgery and radiation therapy, unless the radiation is low dose, does not involve mucosa and is non-myelosuppressive. Patient must have recovered (grade 0-1) from all reversible toxicity related to prior chemotherapy and have adequate washout from prior chemotherapy and investigational agents as follows: Washout period is the longest of one of the following:
  • two weeks
  • standard cycle length of prior regimen (i.e. 21 days for irinotecan q 3 weeks).
  • 10 half-lives for investigational drugs.
  • ECOG performance status of 0, 1 or 2.
  • Laboratory Requirements: (must be done within 7 days prior to registration) Hematology: Absolute granulocytes (AGC) ≥ 1.0 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 90 g/L Chemistry: Serum creatinine ≤ 1.5 x UNL OR Creatinine clearance ≥ 50 ml/min Bilirubin * ≤ UNL AST and ALT ≤ 3.0 x UNL Potassium ≤ UNL Calcium ≤ UNL Magnesium ≥ 0.5 mmol/L (may be achieved with supplementation) Blood glucose (fasting) < 7.8 mmol/L Coagulation: INR ≤ 2 x UNL (* direct, if patient known to have Gilberts)
  • Patient must consent to provision of, and investigator(s) must confirm access to and agree to submit at the request of the NCIC CTG Central Tumour Bank, a representative formalin fixed paraffin block of tumour tissue in order that the correlative marker assays may be conducted. Where local centre regulations prohibit submission of blocks of tumour tissue, the approval of the NCIC CTG must be sought prior to registration of the first patient to allow a predetermined number of slides of representative tumour tissue to be substituted in response to the Central Tumour Bank request. Failure to submit any tissue samples on request will result in the patient being considered ineligible. Where no previously resected or biopsied tumour tissue exists, on the approval of the NCIC CTG, the patient may still be considered eligible for the study.
  • Age ≥ 18 years. (Note that the lower age limit at each centre will be determined by that centre's policy regarding the age at which an individual may sign their own consent.)
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to registration. Patients of reproductive potential must agree to use highly effective contraception as follows:
  • Female study subjects: during study and for 6 months after final dose of study therapy
  • Male study subjects: during study and until 16 weeks after final dose of study therapy.
  • Female partner of male study subject: during study and until 16 weeks after final dose of study therapy
  • Patient consent for trial participation must be obtained according to local Institutional and/or University Human Experimentation Committee requirements. It will be the responsibility of the local participating investigators to obtain the necessary local clearance, and to indicate in writing to the NCIC CTG Study Coordinator that such clearance has been obtained, before the trial can commence in that centre. Because of differing requirements, standard consent forms for the trial will not be provided but sample forms are provided. A copy of the initial full board Research Ethics Board (REB) approval and approved consent forms must be sent to the central office. The patient must sign the consent forms prior to registration. Please note that the consent forms for this study must contain a statement which gives permission for qualified representatives of the CCTG, monitoring agencies and regulatory authorities to review patient records.
  • Patients must be accessible for treatment and follow-up. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up. Patients enrolled in this trial must be treated and followed at the participating centre. This implies there must be a reasonable geographical limit (for example: 2 hour's driving distance) placed on the patients being considered for this trial.
  • Protocol treatment is to begin within 5 working days of patient registration.

Who cannot join

  • A history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for > 5 years.
  • Women who are pregnant or breastfeeding.
  • Any active disease condition which would render the protocol treatment dangerous or impair the ability of the patient to receive protocol therapy (e.g. chronic pancreatitis, active chronic hepatitis, etc.).
  • Any condition (e.g. psychological, geographical, etc.) that does not permit compliance with the protocol.
  • Uncontrolled or significant cardiovascular disease including:
  • Myocardial infarction within 12 months;
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  • Uncontrolled angina within 6 months;
  • Clinically significant congestive heart failure;
  • Stroke;
  • TIA or other ischemic event within 12 months;
  • Severe cardiac valve dysfunction
  • Phase I: Patients may not be diabetic
  • Phase II: Patients may be diabetic, but must have controlled diabetes (fasting glucose < 7.8 mmol/L)
  • Patient has any of the following mood disorders:
  • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (immediate risk of doing harm to others)
  • ≥ CTCAE grade 3 anxiety
  • score of ≥ 10 in the PHQ-9
  • score of ≥ 15 in the GAD-7 mood scale
  • patient selects a positive response of '1, 2, 3' to question number 9 (suicidal ideation) in the PHQ-9
  • Symptomatic metastases in the central nervous system. Subjects with signs or symptoms suggestive of brain metastasis are not eligible unless brain metastases are ruled out by CT or MRI scans.
  • Patients who have received prior EGFR or PI3 Kinase inhibitor therapy.
  • Receipt of an investigational therapeutic agent within washout period defined in section 5.1.4 of the protocol.
  • Severe restrictive lung disease or radiological pulmonary findings of "interstitial lung disease" on the baseline chest x-ray which, in the opinion of the investigator, represents significant pathology.
  • Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120 (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patients who are unable to swallow capsules.
  • Patients on potent CYP3A Inhibitors/Inducers (must have discontinued > 7 days prior to day 1) or therapeutic doses of warfarin like anticoagulants. Patients may receive low molecular weight heparin if indicated.
  • Patients receiving chronic treatment with steroids or another immunosuppressive agent. Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients who are on a stable low dose corticosteroids treatment (e.g. dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible.
  • Ongoing ocular inflammation or infection.
  • Patients with significant (> grade 2) symptomatic ophthalmologic abnormalities such as:
  • Severe dry eye syndrome
  • Keratoconjunctivitis sicca
  • Patients with known HIV (testing not mandatory) infection.

Trial locations and contacts

3 sites in 1 country.

Canada3 sites

  • Ottawa Hospital Research Institute

    Ottawa, Ontario, K1H 8L6

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

About this study

Official title: Phase I/II Study of the P13Kinase Inhibitor BKM120 Given in Combination With Panitumumab in Patients With Metastatic or Advanced RAS-Wild Type Colorectal Cancer.

For the first phase of this study (phase I), the purpose will be to find the dose of a new drug, BKM120, that can safely be given in combination with standard dose panitumumab.

For the second phase of this study (phase II), the purpose is to find out what effects the combination of BKM120 and panitumumab, in doses found to be safe in the first part of the study, has on patients and their colorectal cancer.

Read the detailed description

This is done by starting with doses of BKM120 at lower than the usual dose. Patients are given BKM120 and panitumumab and are watched very closely to see what side effects they have and to make sure the side effects are not severe. If the side effects are not severe, then more patients are asked to join the study and are given higher doses of BKM120. If severe toxicity is seen, doses of BKM120 and/or panitumumab doses may be lowered in subsequent patients. Patients joining the study later on will normally get higher doses of BKM120 than patients who join earlier. This will continue until a dose is found that causes severe but temporary side effects. Doses higher than that will not be given.

Being tested
BKM120, Panitumumab
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BKM120Drug

    PO; Once daily starting day 1 cycle 1, or 5 out of 7 days every week.

  • PanitumumabDrug

    IV; Every two weeks starting day 1 cycle 1 (i.e. day 1 and 15 each 28 day cycle)

Study groups in NCT01591421
Study groupRoleWhat they receive
BKM120 and PanitumumabExperimentalBKM120 will be given either daily starting day 1 cycle 1or 5 out of 7 days every week, depending on when patient is enrolled on the study, in combination with panitumumab given intravenously every two weeks starting day 1 cycle 1.
Receives: Drug: BKM120; Drug: Panitumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Recommended phase II dose of BKM120 (Phase I Component)

    Determine the safety, tolerability, toxicity profile and dose limiting toxicities of BKM120 and Panitumumab.

    Measured: 24 months

Secondary outcomes (2)

  1. Anti-tumour activity (Phase II Component)

    To assess the anti-tumour activity of BKM120 in combination with panitumumab as evidenced by response rates and early progression rates in patients with K-RAS wild-type metastatic colorectal cancer.

    Measured: 24 months

  2. Translational Research

    To investigate the correlation, if any, between response and molecular biomarkers in archival FFPE tumour.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2012 (estimated)
  2. Study start6 Sep 2012
  3. Primary completion30 Sep 2015
  4. Study completion12 Nov 2019

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01591421
Sponsor's protocol ID
I208
Status last verified
Apr 2020
First submitted
2 May 2012
Last updated
4 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Goodwin R, Jonker D, Chen E, Kennecke H, Cabanero M, Tsao MS, Vickers M, Bohemier C, Lim H, Ritter H, Tu D, Seymour L. A phase Ib study of a PI3Kinase inhibitor BKM120 in combination with panitumumab in patients with KRAS wild-type advanced colorectal cancer. Invest New Drugs. 2020 Aug;38(4):1077-1084. doi: 10.1007/s10637-019-00814-3. Epub 2019 Sep 10.

    PubMed 31506897

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing BKM120 and Panitumumab in people with Metastatic Colorectal Cancer, run by Canadian Cancer Trials Group at 3 sites in Canada.

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 21 inclusion and 32 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 4 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Canada. 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

Recommended phase II dose of BKM120 (Phase I Component) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01591421, which also lists 1 linked publication.

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 4 Aug 2023.

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