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Trial record 1 of 1 for:    Repare "ATTACC"
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Study of RP-3500 With Niraparib or Olaparib in Advanced Solid Tumors (ATTACC)

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ClinicalTrials.gov Identifier: NCT04972110
Recruitment Status : Recruiting
First Posted : July 22, 2021
Last Update Posted : November 23, 2022
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Repare Therapeutics

Brief Summary:
The primary purpose of this study is to assess the safety and tolerability of Niraparib or Olaparib in combination with RP-3500, in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 in combination with Niraparib or Olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor, Adult Drug: RP-3500 Phase 1 Phase 2

Detailed Description:

This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:

  • Evaluate the safety profile and MTD of RP-3500 when administered orally in combination with Niraparib or Olaparib to establish the recommended Phase 2 dose and schedule.
  • Characterize the PK profile of RP-3500 in combination with Niraparib or Olaparib
  • Assess anti-tumor activity associated with RP-3500 in combination with Niraparib or Olaparib
  • Examine biomarker responses and establish a correlation with RP-3500 treatment in combination with Niraparib or Olaparib.

After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 in combination with Niraparib or Olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation, expansion and Phase 2
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1b/2 Study of ATR InhibiTor RP-3500 and PARP Inhibitor Combinations in Patients With Molecularly Selected Cancers (ATTACC)
Actual Study Start Date : July 21, 2021
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase Ib Dose Escalation
Multiple dose levels of RP-3500 for oral administration in combination with Niraparib and/or Multiple dose levels of RP-3500 for oral administration in combination with Olaparib
Drug: RP-3500
RP-3500 (ATR inhibitor) in combination with Niraparib or Olaparib (PARP inhibitors)
Other Names:
  • Niraparib
  • Olaparib

Experimental: Phase 2 Expansion Cohorts
Expansion cohort with RP-3500 + Niraparib and/or Expansion cohort RP-3500 + Olaparib
Drug: RP-3500
RP-3500 (ATR inhibitor) in combination with Niraparib or Olaparib (PARP inhibitors)
Other Names:
  • Niraparib
  • Olaparib




Primary Outcome Measures :
  1. Phase Ib - Safety and Tolerability Tolerability of niraparib or olaparib in combination with RP-3500 by assessing the grade and frequency of adverse events and serious adverse events. [ Time Frame: Up to 30 days after last administration of study intervention ]
    To determine the safety and tolerability of niraparib or olaparib in combination with RP-3500 in patients with advanced solid tumors by assessing the grade and frequency of adverse events and serious adverse events

  2. Primary Phase 1b - Define Maximum Tolerated Dose (MTD) of RP-3500-03 in combination with niraparib or olaparib and Recommended Phase 2 dose (RP2D) and preferred schedule by assessing the frequency of Dose limiting Toxicities observed at each dose level [ Time Frame: At the end of cycle 1 (each cycle is 21 days) ]
    To define the MTD of RP-3500-03 in combination with niraparib or olaparib and determine a recommended Phase 2 dose (RP2D) and preferred schedule by assessing the frequency of Dose limiting Toxicities (DLTs) observed at each dose level

  3. Primary Phase 2 - Assess preliminary anti-tumor activity of RP-3500 with niraparib or olaparib in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria (RECIST 1.1) [ Time Frame: While on study therapy, every 6 weeks for first 5 months and then every 9 weeks thereafter ]
    To preliminarily assess the antitumor activity of RP-3500 with niraparib or olaparib in patients with eligible advanced solid tumors by CT/MRI Response evaluation criteria (RECIST 1.1)


Secondary Outcome Measures :
  1. To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of maximum observed plasma concentration (Cmax). [ Time Frame: Through Cycle 1 and 2 (each cycle is 21 days) ]
    To assess PK parameters of RP-3500 in combination with niraparib or olaparib

  2. To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of time to maximum observed plasma concentration (Tmax) [ Time Frame: Through Cycle 1 and 2 (each cycle is 21 days) ]
    To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of time to maximum observed plasma concentration (Tmax)

  3. To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of area under the plasma concentration-time curve 0-6 hours post dose (AUC0-6). [ Time Frame: Through Cycle 1 and 2 (each cycle is 21 days) ]
    To assess plasma concentrations of RP-3500 and niraparib or olaparib with calculations of area under the plasma concentration-time curve 0-6 hours post dose (AUC0-6).



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female and ≥18 years-of-age at the time of signature of the informed consent
  • Confirmed advanced solid tumors resistant or refractory to standard treatment
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1.
  • Evaluable disease as per RECIST v1.1
  • Next generation sequencing (NGS) report obtained in CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
  • Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
  • Acceptable hematologic and organ function at screening
  • Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
  • Ability to swallow and retain oral medications.

Exclusion Criteria:

  • Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
  • Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 10 days or 5 half-lives (whichever is longer), prior to first dose of study drug.
  • Use of radiotherapy (except for palliative reasons) within 7 days prior to first dose of study drug.
  • History or current condition, therapy, or laboratory abnormality that might confound the study results, or interfere with the patient's participation for the full duration of the study treatment.
  • No other anticancer therapy is to be permitted while the patient is receiving study treatment.
  • Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose.
  • Uncontrolled, symptomatic brain metastases.
  • Uncontrolled high blood pressure
  • History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
  • Presence of other known active invasive cancers.
  • Pregnant or breastfeeding women.
  • Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol and/or follow-up procedures outlined in the protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04972110


Contacts
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Contact: Maria Koehler, MD 857-412-7017 mkoehler@reparerx.com

Locations
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United States, Connecticut
Participating Site #1012 Recruiting
New Haven, Connecticut, United States, 06511
United States, Maryland
Participating Site #1009 Recruiting
Baltimore, Maryland, United States, 21205
United States, Michigan
Participating Site #1015 Recruiting
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Participating Site # 1016 Recruiting
Rochester, Minnesota, United States, 55905
United States, New York
Participating Site # 1008 Recruiting
New York, New York, United States, 10032
United States, Texas
Participating Site # 1001 Recruiting
Houston, Texas, United States, 77030
United States, Utah
Participating Site # 1013 Recruiting
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
Repare Therapeutics
Roche Pharma AG
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Responsible Party: Repare Therapeutics
ClinicalTrials.gov Identifier: NCT04972110    
Other Study ID Numbers: RP-3500-03
First Posted: July 22, 2021    Key Record Dates
Last Update Posted: November 23, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Olaparib
Niraparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents