Rucaparib and Irinotecan in Cancers With Mutations in DNA Repair

NCT03318445 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 169521NCI-2017-02294
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, non-randomized, dose escalation and expansion Phase Ib trial to evaluate the safety and recommended phase II dose of the combination of irinotecan and rucaparib.

Conditions

Solid Tumor, Unspecified, Adult

Keywords

DNA repair mutation

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the proportion of patients with either confirmed complete or partial response (as per RECIST version 1.1) as best overall response over the total population.

  Up to 24 months.

Secondary Outcomes (1)

• Median Response duration

  Up to 24 months

Study Arms (2)

Rucaparib and irinotecan

EXPERIMENTAL

Rucaparib will be taken twice daily by mouth for 7-14 days in 21 or 28 day cycles. Irinotecan will be administered by IV for 90 minutes every 14 days, or every 21 days if not tolerated. During the dose escalation phase, the maximum tolerated dose for combining Rucaparib and irinotecan will be determined. The dose for rucaparib during dose escalation will range from 300 mg to 600 mg, depending on the progression of study. The dose for irinotecan during dose escalation may range from 40 mg/m2 to 150 mg/m2. During the dose expansion phase, patients who have received prior PARP inhibitors will be given rucaparib and irinotecan at the maximum tolerated dose levels determined during the dose escalation phase.

Drug: Rucaparib; Drug: Irinotecan

Rucaparib only

EXPERIMENTAL

During the dose expansion phase, patients who have not received prior PARP inhibitor therapy will take 600 mg of rucaparib by mouth daily. Patients who progress on single-agent rucaparib will be given the option to cross-over to the combination treatment arm and receive rucaparib in combination with irinotecan at the maximum tolerated dose levels determined during dose escalation.

Drug: Rucaparib

Interventions

Rucaparib DRUG

All participants will take rucaparib by mouth

Also known as: Rubraca

Rucaparib and irinotecan; Rucaparib only

Irinotecan DRUG

Patients in the dose escalation phase, and patients in the dose expansion phase who have received prior PARP inhibitor therapy, will be given irinotecan by in combination with rucaparib.

Also known as: Camptosar

Rucaparib and irinotecan

Eligibility Criteria

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

You may qualify if:

• Men and women, 18 years or older
• Understand and voluntarily sign informed consent prior to any study-related assessments or procedures are conducted and are able adhere to the study visit schedule and other protocol requirements.
• Solid tumors with one or more of the following DNA repair defects:
• a. BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK2, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, RAD54L (validated from archival tumor tissue or germ line testing from any Clinical Laboratory Improvement Amendments (CLIA) approved lab). This testing should occur prior to study consent or enrollment.
• Presence of at least one lesion with measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria for response assessment
• Advanced solid tumor malignancy without curative options
• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1.
• Adequate organ function:
• Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
• Hemoglobin (Hgb) ≥9g/dL; (last transfusion cannot be within 7 days of trial initiation)
• Platelets (plt) ≥ 100 x 109/L
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x Upper Limit Normal (ULN), \<5x in patients with known liver metastases
• Serum total bilirubin ≤ 1.5 x ULN
• Creatinine\<1.5 x ULN or estimated Glomerular filtration rate (GFR) ≥ 50ml/min by Cockcroft-Gault (http://www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation/)
• The effects of rucaparib on the developing fetus are unknown. Therefore a. Given the results of the embryo-fetal development study, in which rucaparib was embryotoxic at all doses administered, females of childbearing potential and their male partners are advised to practice a highly effective method of contraception during treatment with rucaparib and for 1 month following the last dose for females and 4 months following the last dose for males. A woman is considered to be of childbearing potential unless one of the following applies: i. Is considered to be permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy.

You may not qualify if:

• Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study at clinician's discretion and not otherwise stated below.
• Allergic reaction to single-agent rucaparib or irinotecan.
• Myelodysplastic features on peripheral blood smear
• Prior allergic reaction or known intolerance to irinotecan
• Known Gilbert's disease
• Poorly controlled or symptomatic central nervous system (CNS) metastases or carcinomatous meningitis
• Note: Patients with previously treated brain metastases may participate, 2 weeks after gamma knife (or equivalent) or 4 weeks after Whole Brain Radiotherapy (WBRT), provided they are stable (without evidence of progression by imaging and have not been using steroids for at least 7 days prior to study treatment.
• \. Pregnancy and breast feeding
• \. Inability to comply with study procedures or willingness to use adequate birth control
• \. PARP inhibitors (PARPi) naïve or prior exposure to PARPi therapy
• Patients in Arm 1 of the Dose Expansion cohort cannot have prior exposure to PARPi therapy.
• Patients in Arm 2 of the Dose Expansion cohort cannot be PARPi naïve.

Sponsors & Collaborators

• Pamela Munster: lead
• Clovis Oncology, Inc.: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

rucaparib; Irinotecan

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Pamela Munster, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Medicine; Director, Early Phase Clinical Trials Unit

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 23, 2017
• Study Start: January 12, 2018
• Primary Completion: March 1, 2021
• Study Completion: March 1, 2021
• Last Updated: March 4, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)