ARQ761 + PARP Inhibitor in Refractory Solid Tumors

NCT03575078 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: STU 052018-073
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (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.

  Day 1-28

Secondary Outcomes (1)

• Dose limiting toxicities

  4 weeks

Study Arms (1)

Maximum tolerated dose of ARQ761 in combination with Olaparib.

EXPERIMENTAL

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

Drug: ARQ761, Olaparib

Interventions

ARQ761, Olaparib DRUG

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

Maximum tolerated dose of ARQ761 in combination with Olaparib.

Eligibility Criteria

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

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

MeSH Terms

Conditions

Lymphoma

Interventions

olaparib

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Muhammad Beg

  UTexas Southwestern

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Phase 1 Dose Escalation

Study Record Dates

• First Submitted: June 21, 2018
• First Posted: July 2, 2018
• Study Start: June 25, 2018
• Primary Completion: May 15, 2019
• Study Completion: May 15, 2019
• Last Updated: September 25, 2019

Record last verified: 2019-09