A Phase I, Open-Label, 2 Part Multicentre Study to Assess the Safety and Efficacy of Olaparib in Combination With Carboplatin in Patients With Advanced HER-2 Negative Breast Cancer

NCT02561832 | Terminated Phase 1 Results

• 1 other identifier: D081EC00001
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 7

Brief Summary

This is an open-label study to assess the safety, tolerability and efficacy of olaparib in combination with carboplatin. There are two parts in this study: Part A, a dose escalation in patients with advanced Human Epidermal Growth Factor 2 (HER-2) negative breast cancer and Part B, a dose expansion in the neoadjuvant treatment of HER-2 negative breast cancer patients with germline Breast Cancer Susceptibility Gene (BRCA)1/2 mutations.

Conditions

Breast Cancer

Keywords

breast cancer

Outcome Measures

Primary Outcomes (1)

• Part A: Number of Subjects Reporting Adverse Events (AEs)

  Treatment-emergent AEs (TEAEs) defined as events occurring on or after cycle 1, day 1 up to and including 30 days after last dose (approximately 114 days).

  From day 1 cycle 1, up to and including 30 days after last dose

Study Arms (1)

Arm 1

EXPERIMENTAL

Part A: ascending doses of olaparib in combination with carboplatin will be administered to investigate safety and tolerability and to define the MTD and/or RD for part B. Patients will be treated with this combination up to cycle 4, after cycle 4 they can continue with combination or monotherapy (carboplatin or olaparib). Cohorts will be started sequentially, based on SRC recommendation. Part B will start after MTD/RD identification in part A. Patients will receive olaparib and carboplatin combination for first 4 cycles (21 days per cycle), at the dose, frequency and schedule recommended from Part A. This will be followed by another 4 cycles of standard cancer therapy consisting of anthracycline and cyclophosphamide regimen. Total of 8 treatment cycles will be given before final surgery

Drug: Olaparib; Drug: Carboplatin; Drug: Anthracycline; Drug: Cyclophosphamide

Interventions

Olaparib DRUG

tablets taken orally twice daily

Arm 1

Carboplatin DRUG

intravenous injections on day one of each cycle

Arm 1

Anthracycline DRUG

The choice of anthracycline and cyclophosphamide (AC) regimen in Part B will be up to local Investigator following international guidelines

Arm 1

Cyclophosphamide DRUG

The choice of anthracycline and cyclophosphamide (AC) regimen in Part B will be up to local Investigator following international guidelines

Arm 1

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged ≥18 years
• Normal organ and bone marrow function, measured within 28 days prior to administration of study treatment
• Eastern Cooperative Oncology Group performance status of 0-1
• Postmenopausal or evidence of non-childbearing status for women of childbearing potential.
• Additional for patients participating in Part A only
• Advanced or metastatic breast cancer that is HER-2 negative (HR positive or HR negative)
• Between 0 and 2 lines of prior cytotoxic chemotherapy. Additional for patients participating in Part B only
• Patients with operable breast adenocarcinoma and no evidence of metastatic disease are allowed.
• Patient must meet at least one of the following criteria: Clinical primary tumour size defined as T2 or above, clinical or patho-histological evidence of regional lymph nodes involvement (N+), grade 2-3 disease
• Availability of formalin fixed, paraffin embedded tumour sample from diagnostic biopsies (Not Applicable for patients at sites in Israel)
• Histological confirmation of HER-2 negative breast cancer
• Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious

You may not qualify if:

• Exposure to an investigational product within 30 days or 5 half-lives (whichever is the longer) prior to enrolment
• Prior use of Poly ADP Ribose Polymerase (PARP) inhibitors
• Patients with a known hypersensitivity to olaparib or carboplatin
• Concurrent treatment with an ovarian hormonal replacement therapy or with hormonal agents such as raloxifene, tamoxifen or other selective estrogen receptor modulator. Patient must have discontinued use of such agents 3 weeks prior to beginning study treatment. Luteinising hormone-Releasing hormone (LHRH) analogues are allowed for all patients in Part A.
• Concomitant use of known potent Cytochrome P450 3A4 (CYP3A4) inhibitors and inducers
• Persistent toxicities (Common Terminology Criteria for Adverse Event (CTCAE) grade ≥2 and neuropathy CTCAE \> grade 1) caused by previous cancer therapy, excluding alopecia - Patient with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML
• Patient must have recovered from any effects of any major surgery
• Patient considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled seizures or active uncontrolled infection
• Patient with known active Hepatitis B or C, or Human immunodeficiency virus (HIV)
• Other malignancy within the last 5 years (few exceptions apply). Additional for patients participating in Part A only
• Prior chemotherapy within 3 weeks of study entry
• Other anti-cancer therapy (eg, targeted biotherapy of hormonal agents) within 3 weeks of study entry
• Radiation therapy within 4 weeks or radionuclide treatment within 6 weeks of treatment start
• Prior use of platinum compound in the advanced or metastatic setting. Previous exposure to platinum compounds is allowed only if they were used in early adjuvant or neoadjuvant setting with relapse occurring \>6 months after the last platinum administration and if there is no residual toxicity
• Patient with a history of treated Central Nervous System (CNS) metastases are eligible, provided they meet certain protocol-specified criteria.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (7)

Research Site

New York, New York, 10065, United States

Location

Research Site

Stony Brook, New York, 11794, United States

Location

Research Site

Barcelona, 08035, Spain

Location

Research Site

Madrid, 28034, Spain

Location

Research Site

Madrid, 28050, Spain

Location

Research Site

Valencia, 46010, Spain

Location

Research Site

Zaragoza, 50009, Spain

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

olaparib; Carboplatin; Anthracyclines; Cyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

Early termination leading to a small number of subjects analyzed (N=15).

Results Point of Contact

• Title: Carsten Goessl MD
• Organization: AstraZeneca Pharmaceuticals LP

Carsten.Goessl@astrazeneca.com

+1 2404490654

Study Officials

• Judith Balmana

  Hospital Vall d'Hebron, Barcelona, Spain

  PRINCIPAL INVESTIGATOR

• Tiffany Traina

  Memorial Sloan Kettering Cancer Center, New York, USA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: September 28, 2015
• Study Start: November 6, 2015
• Primary Completion: September 30, 2016
• Study Completion: February 1, 2017
• Last Updated: February 20, 2019
• Results First Posted: February 20, 2019

Record last verified: 2018-10

Locations

US (2); ES (5)