Study of the Combination of BKM120 and Cisplatin or Carboplatin in Patients With Advanced Solid Tumors

NCT02439489 | Completed Phase 1

• 1 other identifier: FM-11-F01b
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

PI3K signaling is a hallmark of many cancers. Subsets of cancers become dependent on PI3K pathway signaling as a result of mutations of the PIK3CA gene itself or of regulators of PI3K (e.g. PTEN, HER2). As a consequence, pathway mutated tumors are particularly sensitive towards PI3K-pathway inhibition. BKM120 is a potent and highly specific oral pan-class I PI3K-inhibitor. The study FM-11-F01b is a phase Ib single institution study using the combination of BKM120 and cisplatin or carboplatin in patient with pathologically confirmed recurrent or metastatic advanced solid tumor, for which treatment with a platinum agent is indicated (preferentially head and neck, NSCLC, ovary, endometrial). The primary objective of the study is to define the phase II recommended dose of daily oral BKM120 and cisplatin (Group 1) or carboplatin (Group 2), given intravenously (IV) on day 1 every 3 weeks.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Number of participants with dose limiting toxicities in each of the study dose levels

  Determination of phase II recommended dose of daily oral BKM120 and cisplatin (Group 1) or carboplatin (Group 2), based upon drug related Dose Limiting Toxicities as described in the protocol at the end of Cycle 1 (each cycle is 22 days)

  36 months

Secondary Outcomes (1)

• Response rate

  36 months

Study Arms (2)

BKM120-CIS

EXPERIMENTAL

BKM120 (60, 80 100 mg po continuously) and Cisplatin (iv 75 mg/m2)

Drug: BKM120-CIS

BKM120-CARBO

EXPERIMENTAL

BKM120 and (60, 80 100 mg po continuously) and Carboplatin (iv AUC 5)

Drug: BKM120-CARBO

Interventions

BKM120-CIS DRUG

BKM120 will be delivered orally once daily on continuous at the dose of 60 mg (dose level 1), 80 mg (dose level 2) and 100 (dose level 3). Cisplatin will be delivered intravenously at the dose of 75 mg/m2 on day 1 every 3 weeks at each dose level of BKM120. In the absence of BKM120 DLT, each level will be administered to 3 patients A minimum of 2 cycles per each dose level will be administered in the absence of disease progression or toxicity

Also known as: Buparlisib (BKM120), CISPLATINO TEVA

BKM120-CIS

BKM120-CARBO DRUG

BKM120 will be delivered orally once daily on continuous at the dose of 60 mg (dose level 1), 80 mg (dose level 2) and 100 (dose level 3). Carboplatin will be delivered intravenously at AUC 5 on day 1 every 3 weeks at each dose level of BKM120. Should dose level 3 be completed, carboplatin will be given at AUC 6 and BKM120 at 100 mg. In the absence of BKM120 DLT, each level will be administered to 3 patients A minimum of 2 cycles per each dose level will be administered in the absence of disease progression or toxicity

Also known as: Buparlisib (BKM120), CARBOPLATIN TEVA

BKM120-CARBO

Eligibility Criteria

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

You may qualify if:

• Patient has provided a signed Informed Consent Form (ICF) obtained prior to any screening procedure;
• Patient is ≥ 18 years at the day of consenting to the study
• Patient has an ECOG performance status ≤ 1
• Pathologically confirmed recurrent or metastatic advanced solid tumor, for which treatment with a platinum agent is indicated
• Life expectancy ≥ 6 months
• Patient has adequate bone marrow and organ function
• Patient must be able to swallow and retain oral medication
• Patient may have received more than 1 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease
• Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
• Patients may receive concurrent radiation therapy to painful bone metastases or areas of impending bone fracture
• Patients must be disease-free of other prior invasive cancers for \> 5 year
• Patients must complete all screening assessments as outlined in the protocol

You may not qualify if:

• Patient has received previous treatment with PI3K and/or mTOR inhibitors
• Patient has received chemotherapy or targeted anticancer therapy ≤ 4 weeks prior to starting study drug or has not recovered from side effects of such therapy
• Patient has symptomatic CNS metastases (Patients with controlled and asymptomatic CNS metastases may participate in this trial)
• Patient has any of the below mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 10 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 ideation in the PHQ-9 (independent of the total score of the PHQ-9)
• Patient is concurrently using other approved or investigational antineoplastic agent
• Patient has received wide field radiotherapy ≤ 4 weeks prior to starting study drug
• Patient has had major surgery within 2 weeks days prior to starting study drug;
• Patients with diabetes mellitus or steroid-induced diabetes mellitus or known intolerance to glucides or fasting glucose \> 120 mg/dL or HbA1c \> 8 %
• Patient has important cardiac disease
• LVEF \< 50%; NYHA Class III or IV
• QTc \> 480 msec; Congenital long QT syndrome
• Clinically significant resting bradycardia
• Complete left bundle branch block; Right bundle branch block + left anterior hemiblock
• Patient has impairment of GI function or GI disease
• Patient receiving chronic treatment with steroids or another immunosuppressive agent.

Sponsors & Collaborators

• Fondazione Michelangelo: lead

Study Sites (1)

Ospedale San Raffaele

Milan, MI, 20100, Italy

Location

MeSH Terms

Interventions

NVP-BKM120

Study Officials

• Luca Gianni, MD

  Ospedale San Raffaele

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: May 8, 2015
• Study Start: December 1, 2012
• Primary Completion: June 9, 2017
• Study Completion: December 31, 2017
• Last Updated: June 20, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)