Olaparib + Sapacitabine in BRCA Mutant Breast Cancer

NCT03641755 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 18-223
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying a combination of drugs as a possible treatment for breast cancer with a BRCA mutation. The interventions involved in this study are:

• Sapacitabine (CYC682)
• Olaparib (Lynparza™)

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD)

  The dose level immediately below the maximally-administered dose (MAD; defined as the dose level where at least two participants develop dose-limiting toxicity \[DLT\]) will be defined as the MTD. In the situation where none of the dose levels have ≥ 2 DLTs, the MTD will be the highest dose administered. The MTD will be established in a minimum of 6 participants.

  Assessed from the time of the first patient registration to the time that the last patient comes off protocol therapy in the dose escalation phase, up to 41 months

• Recommended Phase II dose (RPIID)

  The highest dose level below the MAD at which ≤1 out of 6 patients develop DLT. The RPIID will be established in a minimum of 6 participants.

  Assessed from the time of the first patient registration to the time that the last patient comes off protocol therapy, up to 41 months

• Objective Response Rate

  Defined as the percentage of patients achieving a complete response (disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits \["non-CR/non-PD" in non-target lesions\]; and no new lesions) based on RECIST 1.1

  Assessed for each patient from the time of registration until 30 days after removal from protocol therapy or until death, whichever occurs first, up to 41 months

Secondary Outcomes (2)

• Progression-Free Survival

  Assessed for each patient from the time of registration until 30 days after removal from protocol therapy or until death, whichever occurs first, up to 41 months

• Dose Limiting Toxicity

  Assessed for each patient from the start of protocol therapy to the end of the first cycle of therapy (28 days post start of therapy)

Study Arms (4)

Dose Level -1: Sapacitabine (100 mg) + Olaparib (300 mg)

EXPERIMENTAL

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Drug: Sapacitabine; Drug: Olaparib

Dose Level 1: Sapacitabine (150 mg) + Olaparib (300 mg)

EXPERIMENTAL

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Drug: Sapacitabine; Drug: Olaparib

Dose Level 2: Sapacitabine (200 mg) + Olaparib (300 mg)

EXPERIMENTAL

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Drug: Sapacitabine; Drug: Olaparib

Dose Level 3: Sapacitabine (250 mg) + Olaparib (300 mg)

EXPERIMENTAL

* Olaparib will be administered orally twice daily for each 28-day cycle * Sapacitabine will be administered orally once daily on days 1 - 5 and 8 - 12 of every 28-day cycle

Drug: Sapacitabine; Drug: Olaparib

Interventions

Sapacitabine DRUG

Sapacitabine may help to stop the growth of some types of cancers

Also known as: CYC682

Dose Level -1: Sapacitabine (100 mg) + Olaparib (300 mg); Dose Level 1: Sapacitabine (150 mg) + Olaparib (300 mg); Dose Level 2: Sapacitabine (200 mg) + Olaparib (300 mg); Dose Level 3: Sapacitabine (250 mg) + Olaparib (300 mg)

Olaparib DRUG

Olaparib is an inhibitor of PARP (poly \[adenosine diphosphate-ribose\] polymerase), which means that it stops PARP from working

Also known as: Lynparza

Dose Level -1: Sapacitabine (100 mg) + Olaparib (300 mg); Dose Level 1: Sapacitabine (150 mg) + Olaparib (300 mg); Dose Level 2: Sapacitabine (200 mg) + Olaparib (300 mg); Dose Level 3: Sapacitabine (250 mg) + Olaparib (300 mg)

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed breast cancer that is metastatic or unresectable.
• Documented germline mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function). Testing may be completed by any CLIA-certified laboratory.
• Patients with estrogen and/or progesterone receptor-positive disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy.
• Patients with HER2-positive disease must have received and progressed on two lines of HER2-directed therapy in the metastatic setting.
• Age ≥ 18 years
• ECOG performance status of 0-1 (please see Appendix A).
• Participants enrolling to the phase I portion of the study must have evaluable or measurable disease; participants enrolling to the phase II portion of the study must have measurable disease per RECIST 1.1 criteria (please see Section 11).
• Adequate organ and bone marrow function as defined below:
• Hemoglobin ≥ 10 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
• Platelet count ≥ 100 × 109/L
• Total bilirubin ≤ 1.5 × institutional upper limit of normal (ULN)
• AST(SGOT) / ALT (SGPT) ≤ 2.5 × institutional ULN, OR
• AST(SGOT) / ALT (SGPT) ≤ 5 × institutional ULN if liver metastases are present
• Creatinine Clearance estimated (using the Cockcroft-Gault equation) of ≥ 51 mL/min

You may not qualify if:

• Any previous treatment with a PARP inhibitor, including but not limited to olaparib.
• Any previous treatment with sapacitabine.
• Patients who have had prior systemic chemotherapy, immune therapy, or investigational therapy within 3 weeks of study entry. Endocrine therapy must have been discontinued at least 7 days prior to Cycle 1 Day 1. Patients may receive bisphosphonates or denosumab during the study.
• Patients who have received prior radiotherapy within 1 week of study entry.
• Participants with active pneumonitis.
• Patients who have undergone major surgery or have ongoing persistent toxicities within 2 weeks prior to study entry. Patients must have recovered to baseline or ≤ Grade 1 from any effects of any major surgery prior to study entry with the exception of any grade of alopecia and persistent grade ≤ 2 peripheral neuropathy
• For enrollment during phase II: patients who have received more than 3 prior lines of cytotoxic chemotherapy for metastatic disease. Prior treatments with hormonal therapy and non-hormonal targeted therapy are allowed and not counted as a prior line of cytotoxic chemotherapy. For the purposes of this protocol, the combination of an aromatase inhibitor and everolimus is not considered cytotoxic chemotherapy.
• Patients with a history of treated central nervous system (CNS) metastases are eligible, provided they meet all of the following criteria:
• Disease outside the CNS is present
• No clinical evidence of progression in the CNS since completion of CNS-directed therapy
• Minimum of 2 weeks between completion of radiotherapy and Cycle 1 Day 1
• Recovery from significant (≥ Grade 3) acute toxicity with no requirement for escalating doses of corticosteroid over the 7 days prior to treatment start.
• Participants requiring concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to study entry is 2 weeks.
• Participants requiring concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to study entry is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Participants with a QTcF of \>470 msec on screening ECG.

Sponsors & Collaborators

• Cyclacel Pharmaceuticals, Inc.: collaborator
• Dana-Farber Cancer Institute: lead
• AstraZeneca: collaborator

Study Sites (2)

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Broad Institute of MIT

Cambridge, Massachusetts, 02142, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sapacitabine; olaparib

Condition Hierarchy (Ancestors)

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

Study Officials

• Filipa Lynce, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 20, 2018
• First Posted: August 22, 2018
• Study Start: October 1, 2018
• Primary Completion: April 27, 2022
• Study Completion (Estimated): October 22, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)