NCT01623349

Brief Summary

This research study is a Phase I clinical trial. Phase I clinical trials test the safety of an investigational combination of drugs. Phase I studies also try to define the appropriate dose of the investigational combination to use for further studies. "Investigational" means that the combination of these drugs is still being studied and that research doctors are trying to find out more about it. It also means that the FDA has not approved either of these drugs nor the combination of being tested for use in patients, including people with your type of cancer. BKM120, BYL719 and olaparib are drugs that may stop cancer cells from growing abnormally. These drugs when combined in laboratory experiments with animals, have demonstrated anti-cancer activity. Information from these other research studies suggests that the following agents BKM120, BYL719 and olaparib, may help to shrink tumor cells in the types of cancers being studied in this research study. In this research study, the investigators are looking for the highest dose that can be given safely and also to see if the combination of BKM120 or BYL719 and olaparib is effective in treating your type of cancer.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
118

participants targeted

Target at P75+ for phase_1 ovarian-cancer

Timeline
Completed

Started Sep 2012

Longer than P75 for phase_1 ovarian-cancer

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 7, 2012

Completed
13 days until next milestone

First Posted

Study publicly available on registry

June 20, 2012

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2012

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2019

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2020

Completed
Last Updated

February 10, 2021

Status Verified

February 1, 2021

Enrollment Period

6.7 years

First QC Date

June 7, 2012

Last Update Submit

February 8, 2021

Conditions

Ovarian CancerBreast Cancer

Keywords

RecurrentHigh GradeSerousTriple Negative

Outcome Measures

Primary Outcomes (1)

  • Determine MTD and RP2D of the Combination of BKM120 and Olaparib, and the Combination of BYL719 and Olaparib

    To determine the maximally tolerated dose (MTD) and recommended phase 2 dose (RP2D) of the combination of BKM120 and olaparib, and the combination of BYL719 and olaparib in patients with recurrent TNBC and HGSC.

    2 years

Secondary Outcomes (4)

  • Determine the overall Safety and Observed Toxicities of combining BKM120 and Olaparib, and combining BYL719 and Olaparib

    2 years

  • Determine Pharmacokinetics of BKM120 and Olaparib, and BYL719 and Olaparib

    2 years

  • Determine preliminary activities of these combinations at the MTD and RP2 dose

    2 years

  • Exploratory Translational Endpoints

    2 years

Study Arms (2)

Arm BKM

EXPERIMENTAL

BKM120 and Olaparib

Drug: BKM120 and Olaparib

Arm BYL

EXPERIMENTAL

BYL719 and Olaparib

Drug: BYL719 and Olaparib

Interventions

BKM120 and OlaparibDRUG

Olaparib twice daily (starting dose 50 mg) and BKM120 once daily (starting dose 40 mg). Both drugs are given orally.

Also known as: Olaparib (NSC 747856), BKM120 (IND 102823)
Arm BKM
BYL719 and OlaparibDRUG

Olaparib twice daily (starting dose 100 mg) and BYL719 once daily (starting dose 250 mg). Both drugs are given orally.

Also known as: Olaparib (NSC 747856), BYL719 (IND 107078)
Arm BYL

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed recurrent high grade serous ovarian cancer or triple negative breast cancer
  • Subjects with recurrent, metastatic triple negative breast cancer must have had at least 1 chemotherapy regimen for metastatic breast cancer or have developed metastatic breast cancer within 1 year of completion of adjuvant chemotherapy
  • Prior therapy for high grade serous ovarian cancer subjects must have included a first-line platinum-based regimen
  • At least 4 weeks since prior radiation therapy, 3 weeks since prior chemotherapy and 6 weeks if the last regimen included BCNU or mitomycin C
  • At least 4 weeks since any small-molecular kinase inhibitors or any other type of investigational agent
  • Life expectancy of at least 4 months
  • Able to swallow and tolerate oral medications

You may not qualify if:

  • Evidence of bowel obstruction, abdominal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of study entry
  • Current dependency on IV hydration or total parental nutrition
  • Diabetes mellitus unless well controlled
  • Pregnant or breast feeding
  • History of grade 3 or 4 toxicities with previous PI3kinase inhibitor or PARP inhibitor
  • Current or active dermatologic diagnoses that would preclude interpretation of skin toxicities of BKM120
  • Receiving any medications or substances that are strong inhibitors or inducers of CYP3A4
  • History of cardiac dysfunction or disease
  • Persistent toxicities (greater than or equal to CTCAE grade 2) caused by previous cancer therapy
  • Major surgery within 14 days of starting study treatment
  • Evidence of coagulopathy or bleeding diathesis
  • History of major depressive episode, bipolar disorder, obsessive/compulsive disorder, schizophrenia, history of suicide attempt or ideation or homicide/homicidal ideation
  • CTCAE grade 3 or greater anxiety
  • Uncontrolled, intercurrent illness
  • Known HIV positive and on combination antiretroviral therapy
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77230, United States

Location

Related Publications (4)

  • Batalini F, Xiong N, Tayob N, Polak M, Eismann J, Cantley LC, Shapiro GI, Adalsteinsson V, Winer EP, Konstantinopoulos PA, D'Andrea A, Swisher EM, Matulonis UA, Wulf GM, Mayer EL. Phase 1b Clinical Trial with Alpelisib plus Olaparib for Patients with Advanced Triple-Negative Breast Cancer. Clin Cancer Res. 2022 Apr 14;28(8):1493-1499. doi: 10.1158/1078-0432.CCR-21-3045.

    PMID: 35149538DERIVED

  • Chi P, Qin LX, Camacho N, Kelly CM, D'Angelo SP, Dickson MA, Gounder MM, Keohan ML, Movva S, Nacev BA, Rosenbaum E, Thornton KA, Crago AM, Francis JH, Martindale M, Phelan HT, Biniakewitz MD, Lee CJ, Singer S, Hwang S, Berger MF, Chen Y, Antonescu CR, Tap WD. Phase Ib Trial of the Combination of Imatinib and Binimetinib in Patients with Advanced Gastrointestinal Stromal Tumors. Clin Cancer Res. 2022 Apr 14;28(8):1507-1517. doi: 10.1158/1078-0432.CCR-21-3909.

    PMID: 35110417DERIVED

  • Przybytkowski E, Davis T, Hosny A, Eismann J, Matulonis UA, Wulf GM, Nabavi S. An immune-centric exploration of BRCA1 and BRCA2 germline mutation related breast and ovarian cancers. BMC Cancer. 2020 Mar 12;20(1):197. doi: 10.1186/s12885-020-6605-1.

    PMID: 32164626DERIVED

  • Konstantinopoulos PA, Barry WT, Birrer M, Westin SN, Cadoo KA, Shapiro GI, Mayer EL, O'Cearbhaill RE, Coleman RL, Kochupurakkal B, Whalen C, Curtis J, Farooq S, Luo W, Eismann J, Buss MK, Aghajanian C, Mills GB, Palakurthi S, Kirschmeier P, Liu J, Cantley LC, Kaufmann SH, Swisher EM, D'Andrea AD, Winer E, Wulf GM, Matulonis UA. Olaparib and alpha-specific PI3K inhibitor alpelisib for patients with epithelial ovarian cancer: a dose-escalation and dose-expansion phase 1b trial. Lancet Oncol. 2019 Apr;20(4):570-580. doi: 10.1016/S1470-2045(18)30905-7. Epub 2019 Mar 14.

    PMID: 30880072DERIVED

MeSH Terms

Conditions

Ovarian NeoplasmsBreast NeoplasmsRecurrence

Interventions

NVP-BKM120olaparibAlpelisib

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Ursula A. Matulonis, M.D.

    Dana-Farber Cancer Institute

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

June 7, 2012

First Posted

June 20, 2012

Study Start

September 1, 2012

Primary Completion

May 1, 2019

Study Completion

December 1, 2020

Last Updated

February 10, 2021

Record last verified: 2021-02

Locations

US(5)