Phase I BKM120/Abraxane in Solid Tumors, Expansion Phase Recurrent Endometrial or Ovarian Cancer

NCT02117817 | Withdrawn Phase 1

• 1 other identifier: 101305
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of the first part of this study or the dose escalation portion of the study is to determine what dose of BKM120 and Abraxane is safe to give when the two drugs are used at the same time in patients who are diagnosed with a solid cancer. A solid cancer is a cancer that does not involve the blood, bone marrow or lymph nodes. Dose escalation determines the least toxic and most effect dose of this drug combination for treatment. Once this dose is established, it will be used for the dose expansion phase of the study where we will determine the effect of BKM120 and Abraxane in women diagnosed with a recurrent endometrial or ovarian cancer. We will see whether the combination of both drugs improves the response and survival of patients treated on the two drug regimen. Also we will try to find out whether there are changes in tumors that can help us determine what patients are more likely to respond to BKM120 and Abraxane.

Conditions

Ovarian Cancer; Endometrial Cancer; Recurrent Ovarian Cancer; Recurrent Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  2 years

Secondary Outcomes (2)

• Response rate (at the end of the 3 months of therapy)

  2 years

• Time to progressive disease

  2 years

Study Arms (1)

Treatment (BKM120 in Combination with Weekly Nabpaclitaxel)

EXPERIMENTAL

Drug: BKM120; Drug: Nabpaclitaxel

Interventions

BKM120 DRUG

Treatment (BKM120 in Combination with Weekly Nabpaclitaxel)

Nabpaclitaxel DRUG

Given IV

Also known as: Abraxane®

Treatment (BKM120 in Combination with Weekly Nabpaclitaxel)

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years with a recurrent solid tumor in the Phase I portion of the trial or in the Phase II portion of the trial a recurrent endometrial or ovarian cancer, not amenable to treatment by surgery, radiotherapy or chemotherapy.
• ECOG performance status £ 2
• Patients must have at least one site of measurable disease defined by RECIST 1.1 criteria. If the patient has received prior radiation therapy one measurable lesion must be outside the irradiated field. Lesions within an irradiated field will be followed as non-target lesions and considered evaluable. If the only site of measurable disease is within a previously irradiated field then 6 months must have elapsed between the completion of radiation therapy and entry on study to be considered measurable.
• Patients with a recurrent ovarian cancer must have received at least one prior platinum containing regimen.
• Patients diagnosed with a platinum sensitive ovarian cancer may be enrolled if they will no longer benefit from treatment with a platinum agent as determined by their physician or it would be detrimental to treat the patient with a platinum agent due to underlying medical problems.
• Adequate bone marrow function as shown by: ANC ≥ 1.0 x 109/L, Platelets ≥ 100 x 109/L, Hgb \> 9 g/dL
• Total calcium (corrected for serum albumin) within normal limits (biphosphonate use for malignant hypercalcemia control is not allowed)
• Magnesium within normal limits for the institution.
• Potassium within normal limits for the institution
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x upper limit of normal (ULN) if liver metastases are present)
• Serum bilirubin within normal range. For patients with liver metastases, serum bilirubin ≤ 1.5 x ULN. For patients with well documented Gilbert Syndrome total bilirubin ≤ 3.0 x ULN with direct bilirubin within normal range. )
• Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min
• Negative serum pregnancy test within 72 hours before starting study treatment in women with childbearing potential defined as sexually mature women who have not undergone a hysterectomy or who have had amenorrhea for at least 12 consecutive months or women who have had six months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 20 pg/mL.
• Patients with Grade 3 or greater peripheral neuropathy.
• Ability to sign informed consent

You may not qualify if:

• Patients who have received prior treatment with a P13K inhibitor.
• Patients who have received prior treatment with Nabplaclitaxel Abraxane®.
• Patients with a known hypersensitivity to BKM120 or to its excipients
• Patients with symptomatic brain metastases are excluded. However, patients with asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases \> 28 days prior to study entry including radiotherapy or surgery. Patients receiving steroids for CNS metastases may not participate on this study.
• Patients with acute or chronic liver disease, renal disease or pancreatitis
• Patients with the following mood disorders as judged by the Investigator, Sub-Investigator or a psychiatrist, or as a 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) or patients with active severe personality disorders (defined according to DSM- IV) are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
• Meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a 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)
• Patients with diarrhea ≥ CTCAE 4.0 grade 2
• Patient has active cardiac disease including any of the following:
• Left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Grated acquisition (MUGA) scan or echocardiogram (ECHO)
• QTc \> 480 msec on screening ECG (using the QTcF formula)
• Angina pectoris that requires the use of anti-anginal medication
• Ventricular arrhythmias except for benign premature ventricular contractions
• Supraventricular and nodal arrhythmias requiring a pacemaker or not controlled with medication

Sponsors & Collaborators

• Rutgers, The State University of New Jersey: lead
• Rutgers Cancer Institute of New Jersey: collaborator
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Ovarian Neoplasms; Endometrial Neoplasms

Interventions

NVP-BKM120; Albumin-Bound Paclitaxel

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Darlene Gibbon, MD

  Rutgers Cancer Institute of New Jersey

  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: April 16, 2014
• First Posted: April 21, 2014
• Study Start: February 1, 2015
• Primary Completion: February 25, 2015
• Study Completion: February 25, 2015
• Last Updated: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share