Solid Tumor, Unspecified, AdultPhase 1NCT03318445
Rucaparib and Irinotecan in Cancers With Mutations in DNA Repair
A Phase 1 study testing Rucaparib and Irinotecan in people with Solid Tumor, Unspecified, Adult, run by Pamela Munster at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Unspecified, Adult
- What is being tested?
- Rucaparib and Irinotecan
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2018to 1 Mar 2021
- 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
- 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:
- 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
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- 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.
- Is postmenopausal, defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 milli-international units per millilitre (mIU/mL) or higher) may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to confirm a postmenopausal state.
- Highly effective contraception is considered to be a method with a < 1% per year failure rate. Recommendations for highly effective contraception while taking rucaparib include: i. Ongoing use of injectable or implantable progesterone ii. Placement of an intrauterine device or intrauterine system iii. Bilateral tubal occlusion iv. Complete (as opposed to periodic) abstinence v. Male sterilization, with appropriate post-vasectomy documentation of absence of sperm in ejaculate
- Additional Inclusion Criteria for Dose Expansion Cohort
- Mandatory biopsy on study entry, if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator)
- PARP inhibitor (PARPi) naïve or prior exposure to PARPi therapy (varies depending on Arm 1 and Arm 2)
- Patients in Arm 1 (single agent rucaparib followed by combination upon progression) must be PARPi naïve. Prior irinotecan is allowed
- Patients in Arm 2 (combination) must have been treated with and progressed on a PARPi previously. Prior irinotecan is allowed.
Who cannot join
- 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
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- 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.
- 8. Pregnancy and breast feeding
- 9. Inability to comply with study procedures or willingness to use adequate birth control
- Additional Exclusion Criteria for Dose Expansion Cohort
- 10. 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California San Francisco
San Francisco, California, 94143
About this study
Official title: Combination Therapy of Rucaparib and Irinotecan in Cancers With Mutations in DNA Repair
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.
Read the detailed description
In dose escalation, patients will receive irinotecan and rucaparib. Irinotecan will be given once every 2 weeks (or 3 weeks if not tolerated) and rucaparib will be given twice daily for 7-14 days. Each cycle will be 28 days in duration unless we need to switch to the intermediate dosing regimen of every 21 days. Both rucaparib and irinotecan will be escalated.
In dose expansion, patients who have received prior PARP inhibitors will go straight to the combination arm of irinotecan and rucaparib. If patients are PARP inhibitor naïve, they can receive single agent rucaparib until progression. Once patients on single agent rucaparib progress, they can choose to go on the combination treatment arm. Patients will continue on treatment until disease progression or intolerable toxicity.
- Conditions
- Solid Tumor, Unspecified, Adult
- Being tested
- Rucaparib, Irinotecan
- Keywords
- DNA repair mutation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RucaparibDrug
Also called Rubraca
All participants will take rucaparib by mouth
IrinotecanDrug
Also called Camptosar
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Rucaparib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 24 months.
Secondary outcomes (1)
Median Response duration
Response duration is defined as the time from initial response to the first documented tumor progression.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2017
- Study start12 Jan 2018
- Primary completion1 Mar 2021
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Solid Tumor, Unspecified, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pamela Munster
- Sponsor type
- University, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Responsible party
- Sponsor-investigator, Pamela Munster, University of California, San Francisco
- Investigators
- Pamela Munster, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03318445
- Sponsor's protocol ID
- 169521
- Other IDs
- NCI-2017-02294
- Status last verified
- Mar 2021
- First submitted
- 18 Oct 2017
- Last updated
- 4 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tsang ES, Dhawan MS, Pacaud R, Thomas S, Grabowsky J, Wilch L, Karipineni S, Kelley RK, Ko AH, Collisson E, Chapman JS, Ueda S, Bergsland EK, Munster P. Synthetic Lethality Beyond BRCA: A Phase I Study of Rucaparib and Irinotecan in Metastatic Solid Tumors With Homologous Recombination-Deficiency Mutations Beyond BRCA1/2. JCO Precis Oncol. 2024 Jun;8:e2300494. doi: 10.1200/PO.23.00494.
PubMed 38865673
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Therapy of Rucaparib and Irinotecan in Cancers With Mutations in DNA Repair
- ClinicalTrials.gov ID
- NCT03318445
- Acronym / sponsor ID
- 169521
- Conditions
- Solid Tumor, Unspecified, Adult
- Keywords
- DNA repair mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Pamela MunsterUniversity, hospital or other
- Collaborators
- Clovis Oncology, Inc.
- Study start
- 12 Jan 2018 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 23 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In dose escalation, patients will receive irinotecan and rucaparib. Irinotecan will be given once every 2 weeks (or 3 weeks if not tolerated) and rucaparib will be given twice daily for 7-14 days. Each cycle will be 28 days in duration unless we need to switch to the intermediate dosing regimen of every 21 days. Both rucaparib and irinotecan will be escalated.
In dose expansion, patients who have received prior PARP inhibitors will go straight to the combination arm of irinotecan and rucaparib. If patients are PARP inhibitor naïve, they can receive single agent rucaparib until progression. Once patients on single agent rucaparib progress, they can choose to go on the combination treatment arm. Patients will continue on treatment until disease progression or intolerable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rucaparib and irinotecan | Experimental | Drug: Rucaparib, Drug: IrinotecanRucaparib 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. |
| Rucaparib only | Experimental | Drug: RucaparibDuring 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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:
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RucaparibAlso: RubracaAll participants will take rucaparib by mouth | Drug | Rucaparib and irinotecan, Rucaparib only |
| IrinotecanAlso: CamptosarPatients 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. | Drug | Rucaparib and irinotecan |
Primary outcome
Overall Response Rate (ORR)
Time frame: Up to 24 months.
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.
1 secondary outcome
Median Response duration
Time frame: Up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2021.
- Derived from this study: PubMed 38865673Tsang ES, Dhawan MS, Pacaud R, Thomas S, Grabowsky J, Wilch L, Karipineni S, Kelley RK, Ko AH, Collisson E, Chapman JS, Ueda S, Bergsland EK, Munster P. Synthetic Lethality Beyond BRCA: A Phase I Study of Rucaparib and Irinotecan in Metastatic Solid Tumors With Homologous Recombination-Deficiency Mutations Beyond BRCA1/2. JCO Precis Oncol. 2024 Jun;8:e2300494. doi: 10.1200/PO.23.00494.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pamela Munster, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Rucaparib and Irinotecan in people with Solid Tumor, Unspecified, Adult, run by Pamela Munster at 1 site in United States.
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 22 inclusion and 13 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: finished, as of the sponsor's last update on 4 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Overall Response Rate (ORR) (time frame: Up to 24 months.). 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 NCT03318445, which also lists 1 linked publication.
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 4 Mar 2021.