Malignant Solid NeoplasmPhase 2NCT05142241
Testing the Combination of Anti-Cancer Drugs Talazoparib and Temozolomide in Patients With Advanced Stage Rare Cancers, RARE 2 Trial
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites in United States.
Trial summary
This phase II trial tests whether combination of talazoparib and temozolomide works to shrink tumors in patients with rare cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Malignant Solid Neoplasm
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Computed Tomography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- 11 Jul 2022to 23 Sep 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy or for whom there is no longer standard of care therapy. Other rare tumor types may be acceptable at the discretion of the principal investigator (PI)
- Patients must not be eligible for a higher priority study, such as a disease specific study of phase 2 or higher or a randomized study. Specifically, patients with pheochromocytoma and paraganglioma at the clinical center will be eligible for this study if they are not eligible for the NCT04394858 due to prior PARP inhibitor, dacarbazine (DTIC) or temozolomide therapy
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions)
- Patients consenting to biopsies must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements
- Prior to entering the study, patients must have:
- >= 3 weeks since completion of radiation therapy or major surgery
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- >= 5 half-lives or 3 weeks (whichever is shorter) since completion of biologic therapy or chemotherapy
- Should be at least 6 weeks out from nitrosoureas and mitomycin C
- >= 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study
- >= 1 week from palliative radiation therapy (patients on study may be eligible for palliative radiotherapy to non-targeted lesions after 2 cycles of therapy at the PI's discretion)
- Recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted
- Adults age >= 18 years; children/adolescents age >= 12 years to 17 years with body surface area (BSA) >= 1.5 m^2
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 8 g/dL
- Total bilirubin =< 1.5 X institutional upper limit of normal (=< 3 x upper limit of normal in the presence of documented Gilbert's syndrome or liver metastases at baseline)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X upper limit of normal (ULN)
- Creatinine clearance >= 60 mL/min/1.73 m^2 OR creatinine for adult patients: =< 1.5 X institutional ULN, for pediatric patients (< 18 years of age):
- 2 to < 6 years (0.8 mg/dL male, 0.8 mg/dL female)
- 6 to < 10 years (1 mg/dL male, 1 mg/dL female)
- 10 to < 13 years (1.2 mg/dL male, 1.2 mg/dL female)
- 13 to < 16 years (1.5 mg/dL male, 1.4 mg/dL female)
- 16 to < 18 years (1.7 mg/dL male, 1.4 mg/dL female)
- Talazoparib and temozolomide can cause fetal harm based on animal reproductive and genetic toxicity studies. For this reason, 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 and for the duration of study participation and for at least 7 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 months after completion of study drug administration. Women of child-bearing potential must have a negative pregnancy test (urine or serum) in the 8 days prior to beginning treatment, and again on cycle 1 day 1 of treatment
- Biopsies are optional on this study. In lieu of baseline biopsies, patients are encouraged to submit at registration archival tumor biopsy tissue from a previous research study or medical care providing it meets the minimum collection and preservations requirements. Criteria for the submission of archival tissue are:
- Tissue must have been collected within 3 months prior to registration
- Patient must not have received any intervening therapy for their cancer since the collection of the tumor sample
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For these patients, an HIV viral load test must be completed within 28 days prior to enrollment
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Sensory/motor neuropathy >= grade 2
- Patients who are receiving any other investigational agents
- Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for >= 1 month without requiring steroid and anti-seizure medication are eligible to participate
- History of allergic reactions attributed to compounds of similar chemical composition to study drugs
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
- Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible. For these patients, HBsAg and anti-HBc tests must be done within 28 days prior to enrollment
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- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). For these patients, an HCV RNA test must be done within 28 days prior to enrollment
- Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because temozolomide and talazoparib have demonstrated fetal harm in animal reproductive studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 1 months following the last dose of study drug
Trial locations and contacts
2 sites in 1 country.
United States2 sites
National Cancer Institute Developmental Therapeutics Clinic
Bethesda, Maryland, 20892
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 2 Talazoparib and Temozolomide
This phase II trial tests whether combination of talazoparib and temozolomide works to shrink tumors in patients with rare cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Talazoparib is an inhibitor of poly adenosine diphosphate-ribose polymerase (PARP), an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Temozolomide is in a class of medications called alkylating agents. It damages the cell's DNA and may kill cancer cells. Giving talazoparib in combination with temozolomide may help shrink advanced rare cancers or stop them from growing.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate the proportion of patients with advanced rare cancers who have objective responses (OR) to treatment with temozolomide and talazoparib.
EXPLORATORY OBJECTIVES:
- To evaluate the proportion of patients alive and progression free at 6 months on study agents.
II. To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens.
III. To examine genomic alterations in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and circulating tumor cells (CTCs) that may be associated with response or resistance.
IV. To evaluate the pharmacodynamic effects of the combination on biomarkers of cell death and epithelial-to-mesenchymal transition in tumor tissue and CTCs.
OUTLINE:
Patients receive talazoparib orally (PO) once daily (QD) on days 1-28 and temozolomide PO QD on days 2-6 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and may optionally undergo biopsy and/or blood sample collection at baseline and on the trial.
After completion of study treatment, patients are followed up for 30 days or until one of the following occurs: patient enrolls on another protocol, patient receives standard of care, or death, whichever comes first.
- Conditions
- Malignant Solid Neoplasm
- Being tested
- Biopsy Procedure, Biospecimen Collection, Computed Tomography, Talazoparib, Temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo blood sample collection
Computed TomographyProcedure or surgery
Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography
Undergo CT
TalazoparibDrug
Also called BMN 673, BMN-673, BMN673
Given PO
TemozolomideDrug
Also called CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (talazoparib, temozolomide) | Experimental | Patients receive talazoparib PO QD on days 1-28 and temozolomide PO QD on days 2-6 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and may optionally undergo biopsy and/or blood sample collection at baseline and on the trial. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Talazoparib; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response
The number of participants with an objective response to treatment, defined as a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Overall Response (OR) = CR + PR with CR indicating the disappearance of all target lesions and PR defined as a 30% or more decrease in the sum of the longest diameter of target lesions.
Measured: Restaging scans were carried out every two cycles (8 weeks) until the end of treatment, an average of 3.3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2021
- Study start11 Jul 2022
- Primary completion26 Sep 2025
- Study completion23 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant Solid NeoplasmStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- A P Chen, Principal investigator, National Cancer Institute LAO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05142241
- Sponsor's protocol ID
- NCI-2021-12858
- Other IDs
- NCI-2021-12858, 000692, 10490, 10490
- Status last verified
- Sep 2026
- First submitted
- 1 Dec 2021
- Last updated
- 14 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 2 Talazoparib and Temozolomide
- ClinicalTrials.gov ID
- NCT05142241
- Acronym / sponsor ID
- NCI-2021-12858
- Conditions
- Malignant Solid Neoplasm
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 11 Jul 2022 (actual)
- Primary completion
- 26 Sep 2025 (actual)
- Study completion
- 23 Sep 2027 (estimated)
- First posted
- 2 Dec 2021 (actual)
- Results
- Posted 12 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial tests whether combination of talazoparib and temozolomide works to shrink tumors in patients with rare cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Talazoparib is an inhibitor of poly adenosine diphosphate-ribose polymerase (PARP), an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Temozolomide is in a class of medications called alkylating agents. It damages the cell's DNA and may kill cancer cells. Giving talazoparib in combination with temozolomide may help shrink advanced rare cancers or stop them from growing.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate the proportion of patients with advanced rare cancers who have objective responses (OR) to treatment with temozolomide and talazoparib.
EXPLORATORY OBJECTIVES:
- To evaluate the proportion of patients alive and progression free at 6 months on study agents.
II. To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens.
III. To examine genomic alterations in circulating tumor deoxyribonucleic acid (DNA) (ctDNA) and circulating tumor cells (CTCs) that may be associated with response or resistance.
IV. To evaluate the pharmacodynamic effects of the combination on biomarkers of cell death and epithelial-to-mesenchymal transition in tumor tissue and CTCs.
OUTLINE:
Patients receive talazoparib orally (PO) once daily (QD) on days 1-28 and temozolomide PO QD on days 2-6 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and may optionally undergo biopsy and/or blood sample collection at baseline and on the trial.
After completion of study treatment, patients are followed up for 30 days or until one of the following occurs: patient enrolls on another protocol, patient receives standard of care, or death, whichever comes first.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (talazoparib, temozolomide) | Experimental | Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Drug: Talazoparib, Drug: TemozolomidePatients receive talazoparib PO QD on days 1-28 and temozolomide PO QD on days 2-6 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT scans and may optionally undergo biopsy and/or blood sample collection at baseline and on the trial. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (32 listed)
- Patients must have histologically confirmed rare solid tumors that have progressed on standard therapy or for whom there is no longer standard of care therapy. Other rare tumor types may be acceptable at the discretion of the principal investigator (PI)
- Patients must have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1, with at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions)
- Patients consenting to biopsies must have a tumor site amenable to biopsy. If avoidable, the lesion for biopsy should not be selected as a target lesion for RECIST measurements
- Prior to entering the study, patients must have:
- Adults age >= 18 years; children/adolescents age >= 12 years to 17 years with body surface area (BSA) >= 1.5 m^2
Key exclusion criteria (9 listed)
- Sensory/motor neuropathy >= grade 2
- Patients who are receiving any other investigational agents
- Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for >= 1 month without requiring steroid and anti-seizure medication are eligible to participate
- History of allergic reactions attributed to compounds of similar chemical composition to study drugs
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver 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 |
|---|---|---|
| Biopsy ProcedureAlso: Biopsy, BIOPSY_TYPE, BxUndergo biopsy | Procedure or surgery | Treatment (talazoparib, temozolomide) |
| Biospecimen CollectionAlso: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen CollectionUndergo blood sample collection | Procedure or surgery | Treatment (talazoparib, temozolomide) |
| Computed TomographyAlso: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial TomographyUndergo CT | Procedure or surgery | Treatment (talazoparib, temozolomide) |
| TalazoparibAlso: BMN 673, BMN-673, BMN673Given PO | Drug | Treatment (talazoparib, temozolomide) |
| TemozolomideAlso: CCRG-81045, Gliotem, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831Given PO | Drug | Treatment (talazoparib, temozolomide) |
Primary outcome
Objective Response
Time frame: Restaging scans were carried out every two cycles (8 weeks) until the end of treatment, an average of 3.3 months.
The number of participants with an objective response to treatment, defined as a complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Overall Response (OR) = CR + PR with CR indicating the disappearance of all target lesions and PR defined as a 30% or more decrease in the sum of the longest diameter of target lesions.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
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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.
A P Chen principal investigator
National Cancer Institute LAO
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Computed Tomography in people with Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 2 sites 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 32 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective Response (time frame: Restaging scans were carried out every two cycles (8 weeks) until the end of treatment, an average of 3.3 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Oct 2026.