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Solid TumorsPhase 1NCT01297452

BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors

A Phase 1 study testing BKM120 days 1 - 21 plus paclitaxel + carboplatin, BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin and BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) in people with Solid Tumors, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitaxel. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors
What is being tested?
BKM120 days 1 - 21 plus paclitaxel + carboplatin, BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin and BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
15 Feb 2011to 29 Mar 2017
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

  • Pathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option. Pathology confirmation must be performed at MSKCC.
  • Age ≥ 18 years
  • ECOG performance status ≤ 1
  • Life expectancy of ≥ 12 weeks
  • Adequate bone marrow function as shown by: ANC ≥ 1.5 x 109/L, Platelets ≥ 100 x 109/L, Hemoglobin > 9 g/dL
  • Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
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  • Magnesium ≥ the lower limit of normal
  • Adequate liver function.
  • Serum bilirubin must be within the upper limit of normal. (ULN). AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
  • Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 55 mL/min
  • Fasting plasma glucose (FPG) ≤120 mg/dL or ≤6.7 mmol/L
  • HbA1c ≤ 8%
  • Negative serum pregnancy test within 14 days before starting study treatment in women with childbearing potential
  • Ability to swallow oral medication
  • EXPANSION COHORT B ONLY: Documented genetic alteration (mutation or homozygous deletion) in the PTEN gene, identified by the MSKCC IMPACT assay platform or other CLIA-approved test.

Who cannot join

  • Patients who have received prior treatment with a P13K inhibitor.
  • Patients with a known hypersensitivity to BKM120 or to its excipients
  • Patients with untreated brain metastases are excluded. However, patients with metastatic CNS tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (incl. radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy
  • Patients with acute or chronic liver, renal disease or pancreatitis
  • Patients with the following mood disorders as judged by the Investigator or a psychiatrist, or as result of patient's mood assessment questionnaire:
  • 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)
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  • ≥ CTCAE grade 3 anxiety
  • At screening, mood rating scores of ≥ 10 on PHQ-9 and/or ≥ 15 on GAD-7, unless overruled by psychiatrist's assessment
  • Patient selects a response of "1, 2, or 3" for question 9 on PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation (independent of the total score of the PHQ-9) Note: The psychiatric judgment overrules the mood assessment questionnaire result/investigators judgment. If mood rating scores do not meet eligibility criteria and/or the investigator deems that a patient has mood disorder that renders the patient ineligible, that patient may not be registered to the study unless there is a subsequent psychiatric clinic consultation in which the psychiatrist overrules the mood assessment questionnaire result/investigator judgment.
  • Patients with diarrhea ≥ CTCAE grade 2
  • Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:
  • ST depression or elevation of ≥ 1.5 mm in 2 or more leads
  • Congenital long QT syndrome
  • History or presence of sustained ventricular arrhythmias or atrial fibrillation
  • Clinically significant resting bradycardia (< 50 beats per minutes) QTc > 480 msec on screening ECG
  • Complete left bundle branch block
  • Right bundle branch block + left anterior hemiblock (bifascicular block)
  • Unstable angina pectoris ≤ 6 months prior to starting study drug
  • Acute myocardial infarction ≤ 6 months prior to starting study drug
  • Other clinically significant heart disease such as congestive heart failure requiring treatment (NYHA Class III or IV) or uncontrolled hypertension (please refer to WHO-ISH guidelines)
  • Patients with uncontrolled diabetes mellitus
  • Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g., active or uncontrolled infection) that could cause unacceptable safety risks or compromise compliance with the protocol
  • 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 with unresolved diarrhea will be excluded as previously indicated
  • Patients who have been treated with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug. Erythropoietin or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be continued
  • Patients who are currently receiving treatment with QT prolonging medication with a known risk to induce Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug. Please refer to Appendix E for a list of prohibited drugs.
  • Patient is currently being treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. Please refer to Appendix B for a list of prohibited CYP 3A4 inhibitors and inducers.
  • Patients who have received systemic corticosteroids ≤ 2 weeks prior to starting study drug. Systemic corticosteroids should not be administered with BKM120 (Usage of steroids as premedications and anti-emetics for paclitaxel and carboplatin, per MSKCC guidelines, is allowed). Steroids given as part of pre-medications for imaging studies are not exclusionary.).
  • Patients who have received chemotherapy or targeted anticancer therapy ≤ 4 weeks (6 weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug or who have not recovered from side effects of such therapy (except alopecia)
  • Patients who have received any continuous or intermittent small molecule therapeutics (excluding monoclonal antibodies) ≤ 5 effective half lives prior to starting study drug or who have not recovered from side effects of such therapy (except alopecia)
  • Patients who have received radiotherapy within ≤ 4 weeks prior to registration
  • Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
  • Patients who are currently taking therapeutic doses of warfarin sodium or any other coumadin-derivative anticoagulant.
  • Patient is currently being treated with olanzapine and/or other drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control. Double barrier contraceptives must be used through the trial by both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
  • Known diagnosis of human immunodeficiency virus (HIV) infection
  • History of another malignancy within 3 years, except cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix
  • Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator
  • More than 2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease
  • Patients with multifocal peripheral sensory alterations or paresthesias (including tingling) interfering with function, per patient report (example: activities of daily living).
  • Patients receiving other investigational therapies
  • Patients receiving herbal preparations/medications
  • Patients with any prior history of whole pelvic radiation therapy (WPRT)
  • EXPANSION COHORT A ONLY: More than one prior cytotoxic chemotherapy regimen (in the setting of recurrent and/or metastatic disease (cytotoxic chemotherapy given as part of neo-adjuvant therapy, adjuvant therapy, or concurrent chemoradiation for curative intent is not included in this exclusion item). This does not apply to Expansion Cohort B.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors

The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitaxel.

Conditions
Solid Tumors
Being tested
BKM120 days 1 - 21 plus paclitaxel + carboplatin, BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin, BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1), BKM120, Paclitaxel + Carboplatin
Keywords
BKM120, CARBOPLATIN, TAXOL (PACLITAXEL), Chemotherapy, 10-192

What participants receive

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

  • BKM120 days 1 - 21 plus paclitaxel + carboplatinDrug

    Patients will receive oral daily BKM120 (days 1 - 21, per dose escalation scheme) plus paclitaxel (175 mg/m2 intravenously, day 1) + carboplatin (AUC 5 intravenously, day 1)on a 21-day cycle. Pegfilgrastim (6 mg/subcutaneously) will be administered on day 2 of each cycle.

  • BKM120 (days 1 - 28, ) plus paclitaxel + carboplatinDrug

    Patients will receive oral daily BKM120 (days 1 - 28, per dose escalation scheme) plus paclitaxel (80 mg/m2 intravenously, days 1, 8 and 15) + carboplatin (AUC 5 intravenously, day 1) on a 28-day cycle.

  • BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)Drug

    BKM120 100 mg (days 1 - 21, per dose escalation scheme) plus paclitaxel (200 mg/m2 intravenously, day 1) + carboplatin (AUC 6 intravenously, day 1) on a 21-day cycle. After enrollment to Groups 1 and 2 has been completed and all patients in Group 1 and 2 have completed the DLT monitoring period, up to 6 additional patients will be enrolled in this EXPANSION COHORT.A

  • BKM120, Paclitaxel + CarboplatinDrug

    BKM120 100 mg per oral, days 1 - 21 Paclitaxel (175 mg/m2) intravenously on Day 1 Carboplatin (AUC 5) intravenously on Day 1 EXPANSION COHORT B

Study groups in NCT01297452
Study groupRoleWhat they receive
BKM120 (days 1 - 21) + paclitaxel + carboplatinExperimentalThis will be a single institution phase I study. The primary objectives are to determine the maximum tolerated dose of BKM120 administered with paclitaxel + carboplatin on both a 21-day cycle with growth factor support (Group 1)
Receives: Drug: BKM120 days 1 - 21 plus paclitaxel + carboplatin; Drug: BKM120, Paclitaxel + Carboplatin
BKM120 (days 1 - 28, ) + paclitaxel + carboplatinExperimentalThis will be a single institution phase I study. The primary objectives are to determine the maximum tolerated dose of BKM120 administered + paclitaxel with carboplatin on a 28-day cycle with growth factor support and a 28-day cycle (Group 2).
Receives: Drug: BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin
BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)ExperimentalEXPANSION COHORT A BKM120 100 mg (days 1 - 21, per dose escalation scheme) plus paclitaxel (200 mg/m2 intravenously, day 1) + carboplatin (AUC 6 intravenously, day 1) on a 21-day cycle. After enrollment to Groups 1 and 2 has been completed and all patients in Group 1 and 2 have completed the DLT monitoring period, up to 6 additional patients will be enrolled in this EXPANSION COHORT A.
Receives: Drug: BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)
BKM120 (days 1 - 21) + paclitaxel + carboplatin exp BExperimentalExpansion Cohort B will be restricted to patients with tumors known to harbor PTEN mutation or homozygous deletion. The regimen in Expansion Cohort B will be the same regimen established in Group 1 of the protocol, with BKM120 (now called buparlisib) at 100 mg/day per oral + paclitaxel (175 mg/m2) + carboplatin (AUC 5), both given intravenously (IV) on day 1 of a 21-day cycle
Receives: Drug: BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin

What is being measured

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

  1. To establish the phase II recommended dose of daily oral BKM120

    for patients with advanced solid tumors, BKM120 in combination with two different schedules of paclitaxel and carboplatin.

    Measured: 2 years

  2. EXPANSION COHORT A:To evaluate the safety and tolerability of daily oral BKM120 (100 mg) + paclitaxel (200 mg/m2) + carboplatin (AUC 6), both given intravenously (IV) on day 1 of a 21-day cycle, with pegfilgrastim support

    Measured: 2 years

  3. EXPANSION COHORT B: To obtain a preliminary description of efficacy of the regimen established in Group 1 among patients with tumors harboring PTEN mutation or homozygous deletion.

    Measured: 2 years

Secondary outcomes (4)

  1. To describe the safety of BKM120 combined with paclitaxel and carboplatin,

    Patients will be evaluated by MD at weekly clinic visits during Cycle 1, on Day 1 of subsequent cycles, and will have additional evaluations if clinically indicated. Toxicities will be assessed according to NCI common toxicity criteria (CTC) version 4.0

    Measured: weekly clinic visits during Cycle 1, on Day 1 of subsequent cycles,

  2. To determine the pharmacokinetic profile of daily BKM120.

    when given in combination with carboplatin and paclitaxel. The area under the curve (AUC0→∞), half-life (t½), and maximum concentration (Cmax) for BKM120 will be determined by noncompartmental analysis.(except for Expansion Cohort B)

    Measured: 2 years

  3. To describe and tabulate the radiographic response rate of BKM120 in combination with carboplatin and paclitaxel,

    there is insufficient sample size to support a formal analysis of response rate. As such, radiographic response data will be tabulated and presented in descriptive form.

    Measured: 2 years

  4. Correlative Tissue Studies

    we will calculate the proportion of cases with positive staining of PTEN along with a 95% confidence interval, using the Clopper and Pearson method for exact small sample inference. For Sequenom Analysis, we will calculate the proportion of cases that are positive for each mutation

    Measured: 2 years

Timeline

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

  1. First posted16 Feb 2011 (estimated)
  2. Study start15 Feb 2011
  3. Primary completion29 Mar 2017
  4. Study completion29 Mar 2017

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
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
45 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01297452
Sponsor's protocol ID
10-192
Status last verified
Mar 2017
First submitted
15 Feb 2011
Last updated
31 Mar 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • Smyth LM, Monson KR, Jhaveri K, Drilon A, Li BT, Abida W, Iyer G, Gerecitano JF, Gounder M, Harding JJ, Voss MH, Makker V, Ho AL, Razavi P, Iasonos A, Bialer P, Lacouture ME, Teitcher JB, Erinjeri JP, Katabi N, Fury MG, Hyman DM. A phase 1b dose expansion study of the pan-class I PI3K inhibitor buparlisib (BKM120) plus carboplatin and paclitaxel in PTEN deficient tumors and with dose intensified carboplatin and paclitaxel. Invest New Drugs. 2017 Dec;35(6):742-750. doi: 10.1007/s10637-017-0445-0. Epub 2017 Mar 9.

    PubMed 28281183

  • Hyman DM, Snyder AE, Carvajal RD, Gerecitano JF, Voss MH, Ho AL, Konner J, Winkelmann JL, Stasi MA, Monson KR, Iasonos A, Spriggs DR, Bialer P, Lacouture ME, Teitcher JB, Katabi N, Fury MG. Parallel phase Ib studies of two schedules of buparlisib (BKM120) plus carboplatin and paclitaxel (q21 days or q28 days) for patients with advanced solid tumors. Cancer Chemother Pharmacol. 2015 Apr;75(4):747-55. doi: 10.1007/s00280-015-2693-z. Epub 2015 Feb 12.

    PubMed 25672916

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BKM120 days 1 - 21 plus paclitaxel + carboplatin, BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin and BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) in people with Solid Tumors, run by Memorial Sloan Kettering Cancer 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 15 inclusion and 43 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 31 Mar 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?

To establish the phase II recommended dose of daily oral BKM120 (time frame: 2 years). The study lists 3 primary outcomes in all. 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 NCT01297452, which also lists 2 linked publications.

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 31 Mar 2017.

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