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

NCT01591421 | Completed Phase 1 DMC

• 1 other identifier: I208
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 3

Brief 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 found to be safe in the first part of the study, has on patients and their colorectal cancer.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (1)

• Recommended phase II dose of BKM120 (Phase I Component)

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

  24 months

Secondary Outcomes (2)

• Anti-tumour activity (Phase II Component)

  24 months

• Translational Research

  24 months

Study Arms (1)

BKM120 and Panitumumab

EXPERIMENTAL

BKM120 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.

Drug: BKM120; Drug: Panitumumab

Interventions

BKM120 DRUG

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

BKM120 and Panitumumab

Panitumumab DRUG

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

BKM120 and Panitumumab

Eligibility Criteria

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

You may qualify if:

• 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
• 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).
• 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:

You may not qualify if:

• 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;
• 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)

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• Pfizer: collaborator

Study Sites (3)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• 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.

  PMID: 31506897 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

NVP-BKM120; Panitumumab

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)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Derek Jonker

  Ottawa Health Research Institute - General Division

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2012
• First Posted: May 4, 2012
• Study Start: September 6, 2012
• Primary Completion: September 30, 2015
• Study Completion: November 12, 2019
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)