AzTrials
AzTrials

LymphomaPhase 1NCT03575078

ARQ761 + PARP Inhibitor in Refractory Solid Tumors

A Phase 1 study testing ARQ761, Olaparib in people with Lymphoma, run by University of Texas Southwestern Medical Center.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Open Label, dose escalation in a 3+3 study design to establish the RP2D of the combination of ARQ761 and a PARP inhibitor, Olaparib Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma
What is being tested?
ARQ761, Olaparib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
25 Jun 2018to 15 May 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed informed consent.
  • Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors that have received standard of care for their disease and for which no other approved therapy is available or if patient has declined other approved therapies.
  • Age ≥ 18 years.
  • Performance status ECOG 0-1.
  • Measurable disease as per RECIST criteria 1.1.
  • Access to archival tissue (available unstained slides of tumor tissue).
Show all 21Show fewer
  • Central venous access, such as a Portacath or Hickman Line.
  • Adequate organ and marrow function measured within 14 days prior to administration.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • Has not undergone a hysterectomy or bilateral oophorectomy; or Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
  • Ability to understand and willing to sign a written informed consent. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
  • Patients must have a life expectancy ≥ 16 weeks.
  • 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) and which is suitable for accurate repeated measurements.
  • Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1.
  • Postmenopausal is defined as:
  • Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
  • Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) levels in the post-menopausal range for women under 50
  • Radiation-induced oophorectomy with last menses >1 year ago
  • Chemotherapy-induced menopause with >1 year interval since last menses
  • Surgical sterilization (bilateral oophorectomy or hysterectomy)

Who cannot join

  • Those whose adverse events from prior therapies have not recovered to ≤ grade 1 except alopecia.
  • Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to study treatment.
  • Concurrent therapy: No other concurrent anticancer or investigational therapy permitted except as noted above.
  • Subjects with known, untreated and/or symptomatic brain metastases: Subjects with known, treated brain metastases must be stable with no symptoms for four weeks after completion of treatment, with image documentation required, and must either be off steroids or on a stable dose of steroids for at least two weeks prior to protocol enrollment.
  • Subjects with known leptomeningeal metastases are excluded, even if adequately treated.
  • Patients with spinal cord compression are excluded unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
Show all 30Show fewer
  • Subjects without known brain metastases do not require radiologic imaging prior to enrollment.
  • Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant pulmonary disease (shortness of breath at rest or mild exertion), uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to agent(s) or other agents used in study.
  • Pregnant or nursing subjects due to the potential for either congenital abnormalities or harming infants who are being nursed, respectively.
  • Involvement in the planning and/or conduct of the study (applies to both AstraZeneca, ArQule staff and/or staff at the study site).
  • Previous enrollment in the present study.
  • Participation in another clinical study with an investigational product during the last 4 weeks.
  • Any previous treatment with PARP inhibitor, including olaparib.
  • Resting ECG with QTc > 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome.
  • Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks.
  • Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents.
  • Patients with myelodysplastic syndrome/acute myeloid leukemia or with features suggestive of MDS/AML.
  • Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery.
  • 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.
  • Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
  • Breast feeding women.
  • Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
  • Patients with a known hypersensitivity to olaparib or any of the excipients of the product.
  • Patients with a known hypersensitivity to ARQ761.
  • Patients with known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids.
  • Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
  • Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable per 3.1.8).
  • Other malignancy within the last 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, or other solid tumors including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for ≥5 years.
  • 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.

About this study

Official title: PHASE 1 DOSE ESCALATION TRIAL OF β-LAPACHONE (ARQ761) IN COMBINATION WITH PARP INHIBITOR, OLAPARIB, FOR REFRACTORY, ADVANCED SOLID TUMORS

Open Label, dose escalation in a 3+3 study design to establish the RP2D of the combination of ARQ761 and a PARP inhibitor, Olaparib

Read the detailed description

Open Label, dose escalation in a 3+3 study design to establish the RP2D of the combination of ARQ761 and a PARP inhibitor, Olaparib. This is an exploratory Phase 1 trial evaluating the safety and tolerability of the combination of ARQ761 and Olaparib.

Conditions
Lymphoma
Being tested
ARQ761, Olaparib
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ARQ761, OlaparibDrug

    ARQ761: weekly infusion. Olaparib Dose 1 D-7 administered orally twice daily

Study groups in NCT03575078
Study groupRoleWhat they receive
Maximum tolerated dose of ARQ761 in combination with Olaparib.ExperimentalARQ761: weekly infusion. Olaparib Dose 1 D-7 administered orally twice daily
Receives: Drug: ARQ761, Olaparib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The maximum tolerated dose of ARQ761 in combination with Olaparib.

    If a dose limiting toxicity (DLT) is observed in 1 out of 3 patients at a given dose level, up to 3 additional patients will be enrolled and treated at that dose level.

    Measured: Day 1-28

Secondary outcomes (1)

  1. Dose limiting toxicities

    DLT will be defined by the occurrence of any of the following toxicities possibly or probably related to treatment, during cycle 1 only:

    Grade 3 or 4 hemolysis or hemolytic anemia, except: Transfusion for hemolysis or hemolytic anemia will be considered a DLT only if Hgb < 8.0 g/dL (Grade 3 anemia) (b) Any drug related grade 3 or grade 4 non-hematological toxicity, except alopecia, nausea, diarrhea and vomiting in the absence of optimal anti-diarrheal and/or anti-nausea medications (c)Grade 4 neutropenia lasting more than 7 days. (d) Platelets <50,000/µl for longer than 7 days or any platelet count <25,000/µl. (e) Grade 3 or 4 hyperbilirubinemia that does not recover to Grade 1 within 7 days

    Measured: 4 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2018
  2. Study start25 Jun 2018
  3. Primary completion15 May 2019
  4. Study completion15 May 2019

Why it stopped: Project Never Initiated - no human subjects were enrolled and no data regarding humans was collected or studied

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Phase 1 Dose Escalation
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03575078
Sponsor's protocol ID
STU 052018-073
Status last verified
Sep 2019
First submitted
21 Jun 2018
Last updated
25 Sep 2019
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ARQ761, Olaparib in people with Lymphoma, run by University of Texas Southwestern Medical Center.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 25 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The maximum tolerated dose of ARQ761 in combination with Olaparib. (time frame: Day 1-28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03575078.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2019.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in