Olaparib in Unresectable/Metastatic Melanoma With BRCA1/2

NCT05482074 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 22-294
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate how effective Olaparib is when given as a treatment for primary or recurrent, unresectable or metastatic melanoma. This research study involves targeted therapy.

• The name of the study drug involved in this study is: Olaparib (also known as Lynparza)

Conditions

Recurrent Metastatic Melanoma; Cutaneous Melanoma; Mucosal Melanoma; Uveal Melanoma

Keywords

Recurrent metastatic melanoma; Cutaneous Melanoma; Mucosal Melanoma; Uveal Melanoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  Best overall response (CR+PR) assessed by RECIST v1.1

  12 weeks

Secondary Outcomes (4)

• Progression Free Survival

  from first dose of treatment until disease progression or death up to 2 years

• Number of participants with treatment-related adverse events

  from first dose of treatment up to 2 years

• Disease Control Rate

  start of treatment until disease progression up to 2 years

• Overall Survival

  defined as the time from start of treatment to the date of death due to any cause up to 5 Years

Study Arms (1)

OLAPARIB

EXPERIMENTAL

The research study procedures include screening for eligibility, study treatment including evaluations, surveys, optional biopsies, and follow up visits Olaparib- Each study treatment cycle lasts 28 days . This will continue for as long as the study treatment is providing clinical benefit

Drug: Olaparib

Interventions

Olaparib DRUG

Oral, twice a day, dosage per protocol, per 28 day cycle

Also known as: LYNPARZA

OLAPARIB

Eligibility Criteria

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

You may qualify if:

• Subjects must have histologically or cytologically confirmed diagnosis of primary or recurrent metastatic melanoma including cutaneous, mucosal, or uveal melanoma.
• Participants must have a germline or somatic DNA damage repair mutation or deletion in BRCA1 or BRCA2. The result may have been obtained from one of the following test providers: OncoPanel, SNaPshot Panel, Myriad Genetics, Invitae, Ambry, Quest, Colour Genomics, IMPACT, Foundation Medicine (tissue or ctDNA based), Guardant, or another CLIA approved tissue and/or serum based next generation sequencing-based assay. (Variants of uncertain significance are excluded.)
• Participants must have measurable disease as defined by RECIST 1.1 criteria
• At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) (or Clinical examination) and which is suitable for accurate repeated measurements.
• Subjects must have received prior checkpoint inhibitor therapy (defined as anti-CTLA4 or anti-PD-1 or combination anti-CTLA4/anti-PD-1), either for metastatic or unresectable disease or progressed on adjuvant therapy.
• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of olaparib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Patients must have a life expectancy ≥ 16 weeks.
• ECOG performance status ≤1(Karnofsky ≥60%, see Appendix A).
• Participants must have adequate organ and marrow function measured within 28 days prior to administration of study treatment as defined below:
• Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelet count ≥ 100 x 109/L
• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be ≤ 5x ULN
• Patients must have creatinine clearance estimated of ≥51 mL/min using the Cockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinine clearance = (140-age \[years\]) x weight (kg) (x F)a / serum creatinine (mg/dL) x 72 (where F=0.85 for females and F=1 for males).

You may not qualify if:

• Participants who have had chemotherapy or radiotherapy (except for palliative reasons) for melanoma within 3 weeks prior to entering the study.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities CTCAE \> Grade 2) with the exception of alopecia.
• Participants who are receiving any other investigational agents.
• Other malignancy unless curatively treated with no evidence of disease for ≥5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy more than three years prior to registration, and that the patient remains free of recurrent or metastatic disease
• Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
• Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment.
• Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
• Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
• 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 starting olaparib is 2 weeks. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product.
• 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 starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
• Any previous treatment with a PARP inhibitor, including olaparib.
• Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g., unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation \>500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
• Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent.
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because olaparib is an agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with olaparib breastfeeding should be discontinued if the mother is treated with olaparib.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• AstraZeneca: collaborator

MeSH Terms

Conditions

Melanoma; Uveal Melanoma

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Eye Neoplasms; Eye Diseases; Uveal Diseases

Study Officials

• Tamara Sussman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 1, 2022
• Study Start: October 4, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: January 19, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu