Advanced/Metastatic Solid TumorsPhase 1NCT04182516
Study of NMS-03305293 in Pts with Selected Advanced/Metastatic Solid Tumors
A Phase 1 study testing NMS-03305293 in people with Advanced/Metastatic Solid Tumors, run by Nerviano Medical Sciences at 10 sites in 5 countries.
Trial summary
Phase I, first-in-human, open-label, multicenter, dose-escalation and dose expansion study with the aim of exploring safety, tolerability and preliminary antitumor activity of NMS-03305293 (a PARP inhibitor) as single agent in adult patients with selected advanced/metastatic, relapsed/refractory solid tumors who have… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/Metastatic Solid Tumors
- What is being tested?
- NMS-03305293
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 25 Nov 2019to 16 May 2024
- 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
- Inclusion Criteria for Dose Escalation and Dose Expansion Part:
- Patients with histologically confirmed diagnosis of locally advanced/metastatic HER2 negative breast cancer, epithelial ovarian cancer, castration-resistant prostate cancer (CRPC) or pancreatic cancer. BRCA1 and BRCA2 mutation status is not required for enrollment in the Dose Escalation part, but enrichment with deleterious/pathogenic or likely pathogenic/suspected deleterious BRCA carriers will be attempted.
- Patients must have progressive disease defined by RECIST 1.1 following standard therapy or be unsuitable for standard therapy. For CRPC patients, disease progression at study entry is defined as one or more of the following three criteria (according to PCWG2):
- PSA progression defined by a minimum of three rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the Screening visit should be ≥ 2.0 ng/ml (µg/L). If the third PSA value is less than second PSA, a fourth PSA must be repeated and if the value is higher than second it must be considered as progressive disease;
- Soft tissue/visceral disease progression defined by RECIST 1.1;
- Bone disease progression defined by two or more new lesions on bone scan.
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- Male or female patients with age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
- Life expectancy of at least 3 months.
- Signed and dated IEC or IRB-approved Informed Consent.
- At least 4 weeks must have elapsed or, in absence of toxicity, 5 half-lives, since completion of prior cancer therapy (at least 6 weeks for nitrosureas, mitomycin C and liposomal doxorubicin) before Cycle 1 Day 1.
- Prior platinum therapy is allowed provided that criteria for platinum refractory disease are not met (see exclusion criterion n.3).
- Resolution of all acute toxic effects (excluding alopecia) of any prior anticancer therapy to NCI CTC (Version 5.0) Grade ≤ 1 or to the baseline laboratory values as defined in Inclusion Criterion Number 10.
- Adequate hematological profile, renal and hepatic functions.
- All patients must agree before enrollment to undergo germline BRCA1 and BRCA2 testing on blood. The test will be performed in a centralized laboratory selected by the sponsor. Availability of an ad hoc blood sample is mandatory for central germline BRCA analysis both in dose escalation and in dose expansion.
- Patients must use effective contraception or abstinence. Female patients of childbearing potential must agree to use effective contraception or abstinence during the period of therapy and in the following 6 months after discontinuation of study treatment. Being NMS-03305293 a potential CYP3A perpetrator, hormonal contraception may lose efficacy while on treatment with NMS-03305293, therefore this should be taken into account. Male patients must be surgically sterile or must agree to use effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment.
- Capability to swallow capsules intact (without chewing, crushing, or opening).
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study indications or procedures.
- Patients must have deleterious/pathogenic germline or likely pathogenic/suspected deleterious BRCA1 or BRCA2 mutation confirmed by the centralized laboratory selected by the Sponsor.
- Measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST) except for CRPC patient who can have non-measurable disease.
- Patients must have received the following previous treatment:
- HER2 negative breast cancer: no more than 3 prior chemotherapy regimens for locally advanced and/or metastatic disease (no limit on prior hormonal therapies or targeted anticancer therapies). At least 1 line of taxane or anthracycline based chemotherapy, if not contraindicated, in adjuvant/neoadjuvant or metastatic setting. If HR (Hormone Receptor) positive, at least 1 line of prior endocrine therapy. Prior treatment with PARP inhibitors is required in the HER2 neg breast cancer cohort pre-treated with a PARP inhibitor
- Epithelial ovarian cancer: no more than 4 prior regimens for locally advanced/metastatic disease including at least 1 line of platinum based hemotherapy;
- CRPC: no more than 4 prior regimens; must have received at least 1 prior NHA (e.g. abiraterone or enzalutamide) and a taxane. Ongoing androgen deprivation therapy with a GnRH analogue or orchiectomy (i.e., surgical or medical castration) is mandatory.
- Pancreatic cancer: no more than 2 prior regimens. Patients may have received prior radiotherapies (not considered as a regimen).
- Patients with controlled, asymptomatic CNS involvement, which has been stable for the previous 4 weeks, are eligible. The use of seizure prophylaxis is allowed as long as patients are taking non-enzyme-inducing anti-epileptic drugs (non-EIAEDs).
Who cannot join
- Current enrollment in another therapeutic clinical trial.
- Prior malignancy except for any of the following:
- Prior BRCA-associated cancer as long as there is no current evidence of the prior cancer;
- Carcinoma in situ or non-melanoma skin cancer;
- A cancer diagnosed and definitively treated ≥ 5 years before enrolment with no subsequent evidence of recurrence;
- Patients with prior platinum therapy exposure who had evidence of disease progression during platinum treatment (refractory disease) and patients whose disease relapsed within 6 months of the last dose of prior adjuvant or neo-adjuvant platinum therapy.
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- Patients who have received prior PARP inhibitors are excluded in the following two cohorts of the Dose Expansion part: HER2 negative breast cancer patients not treated with prior PARP inhibitors and the pancreatic cancer patients cohort. Previous treatment with PARP inhibitors is allowed in the dose escalation part and in the expansion cohorts of ovarian cancer patients and CRPC patients.
- Patients with known symptomatic brain metastases or leptomeningeal involvement. Patients with asymptomatic brain metastases or leptomeningeal involvement are excluded in the Dose Escalation Part only.
- Treatment with systemic immune modulators such as corticosteroids at prednisone-equivalent dose of >10 mg/day, cyclosporine and tacrolimus or radiotherapy within 28 days before Cycle 1 Day 1.
- Prior high-dose chemotherapy with bone marrow or stem cell transplant.
- Major surgery, other than diagnostic surgery, within 4 weeks prior to treatment.
- Any of the following in the past 6 months: myocardial infarction, unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis.
- Pregnancy or breast-feeding women.
- Known active infections (bacterial, fungal, viral including HIV positivity).
- Active gastrointestinal disease (e.g., documented gastrointestinal ulcer, Crohn's disease, ulcerative colitis, or short gut syndrome) or other syndromes that would impact on drug absorption.
- Patients with QTc interval ≥ 460 milliseconds for women, ≥450 for men or with risk factors for torsade de pointes (e.g., heart failure, uncontrolled hypokalemia, family history of long QT syndrome) or receiving treatment with concomitant medications known to prolong the QT/QTc interval that cannot be replaced with another treatment prior to enrolment.
- Patients receiving treatment with concomitant medications known to be CYP2D6 and CYP2C19 sensitive substrates that cannot be replaced with another treatment.
- Other severe acute or chronic medical or psychiatric condition (including history of seizure disorder) or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study or could compromise protocol objectives in the opinion of the Investigator and/or the Sponsor.
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
Bulgaria3 sites
MHAT - Dobrich AD (Department of medical oncology)
Dobrich
MHAT Sveta Sofia EOOD (Department of medical oncology)
Sofia
MHAT Women's Health - Nadezhda OOD (Clinic of medical oncology)
Sofia
Italy3 sites
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Milan, 20123
Istituto Oncologico Veneto IRCCS
Padova, 35128
Centro Ricerche Cliniche di Verona Srl
Verona, 37134
China2 sites
Fudan University Shanghai Cancer Center
Shanghai
TianJin Medical University Cancer Institute & Hospital
Tianjin
United Kingdom1 site
University College London Hospitals NHS Foundation Trust
London
About this study
Official title: A Phase I Dose Escalation Study of NMS-03305293 in Adult Patients with Selected Advanced/Metastatic Solid Tumors
Phase I, first-in-human, open-label, multicenter, dose-escalation and dose expansion study with the aim of exploring safety, tolerability and preliminary antitumor activity of NMS-03305293 (a PARP inhibitor) as single agent in adult patients with selected advanced/metastatic, relapsed/refractory solid tumors who have exhausted standard treatment options or for whom standard therapy is considered unsuitable.
- Conditions
- Advanced/Metastatic Solid Tumors
- Being tested
- NMS-03305293
- Keywords
- HER2 negative breast cancer, Epithelial ovarian cancer, Castration-resistant prostate cancer (CRPC), Pancreatic cancer, BRCA1 Gene Mutation, BRCA2 Gene Mutation
- Medical subject headings
- Carcinoma, Ovarian Epithelial, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NMS-03305293Drug
All patients will receive NMS-03305293 administered orally on Days 1-21 (schedule A) or Days 1-28 (schedule B) in repeated 4-week cycles.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Part | Experimental | Patients with histologically confirmed diagnosis of locally advanced/metastatic HER2 negative breast cancer, epithelial ovarian cancer, castration-resistant prostate cancer (CRPC) or pancreatic cancer. Receives: Drug: NMS-03305293 |
| Dose Expansion Part - Epithelial Ovarian Cancer | Experimental | Patients with gBRCA mutation and epithelial ovarian cancer. Receives: Drug: NMS-03305293 |
| Dose Expansion Part - Pretreated HER 2 Neg. Breast Cancer | Experimental | Patients with gBRCA mutation and HER2 negative breast cancer previously treated with a PARP inhibitor. Receives: Drug: NMS-03305293 |
| Dose Expansion Part - No Pretreated HER 2 Neg. Breast Cancer | Experimental | Patients with gBRCA mutation and HER2 negative breast cancer who have not received prior therapy with a PARP inhibitor. Receives: Drug: NMS-03305293 |
| Dose Expansion Part - CRPC | Experimental | Patients with gBRCA mutation and castration-resistant prostate cancer (CRPC). Receives: Drug: NMS-03305293 |
| Dose Expansion Part - Pancreatic Cancer | Experimental | Patients with gBRCA mutation and pancreatic cancer who have not received prior therapy with a PARP inhibitor. Receives: Drug: NMS-03305293 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with first-cycle dose limiting toxicity
Measured: Time interval between the date of the first dose administration in Cycle 1 (each cycle is 28 days) and the date of the first dose administration in Cycle 2 which is expected to be 28 days or up to 42 days in case of dose delay due to toxicity
Secondary outcomes (14)
Number of participants with Adverse Events (AEs)
Safety will be assessed by AEs, which includes clinically significant abnormalities identified during a medical test (e.g. laboratory tests, vital signs, electrocardiogram, etc.). A treatment-emergent AE is defined as an AE observed after starting administration of the study drug up to 28 days after last dose of study medication intake. AEs will be coded with Medical Dictionary for Regulatory Activities and graded according to The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
Measured: From the Informed Consent signature to 28 days after the last dose of study treatment administration.
Maximum concentration (Cmax) of NMS-03305293 after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Time to observed Cmax (Tmax) of NMS-033052293 after single and multiple doses of drug
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Area under the concentration-time curve to the last of measurable concentration (AUClast) of NMS-033052293 after single and repeated dose of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Terminal elimination half-life (t1/2) of NMS-033052293 after single and multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Area under the plasma concentration vs. time curve to infinity (AUCinf) of NMS-033052293 after multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Accumulation ratio (Rac) of NMS-033052293 after multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Oral plasma clearance (CL/F) of NMS-033052293 after multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Apparent volume of distribution (Vd/F) of NMS-033052293 after multiple doses of drug.
Plasma samples will be collected and used for pharmacokinetics assessments.
Measured: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Renal clearance of NMS-033052293 after multiple doses of drug.
Samples of urine will be used for pharmacokinetics assessments. To be collected in all patients enrolled after the first DLT.
Measured: Schedule A, QD and BID dosing: Cycle 1 (Day 1 and 21). ; Schedule B, QD and BID dosing: Cycle 1 (Day 1 and 28).Cycle lenght is 4 weeks.
Objective tumor response (OR)
Objective tumor response (OR) measured using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. For prostate cancer patients response will be evaluated by RECIST version 1.1/PCWG3 for patients with measurable disease and by Prostatic Specific Antigen (PSA) for all patients through PCWG3 criteria.
Measured: At baseline, every even cycle (Day 28), at the end of treatment and at follow-up, every 8 weeks, till disease progression, an average 18 months.
Progression Free Survival (PFS)
Progression Free Survival (PFS) will be calculated from the date of treatment initiation to the date of first documentation of disease progression according to RECIST 1.1 or RECIST 1.1/PCWG3 for patient with CRPC, or death due to any cause, whichever comes first.
Measured: From date of first dose of study drug up to the date of first documentation of disease progression or death due to any cause, whichever comes first, an average of 2 years.
Time To Progression (TTP)
Time to Progression (TTP) will be evaluated from the date of treatment initiation to the date of first documentation of disease progression according to RECIST 1.1 criteria or RECIST 1.1/PCWG3 for patient with CRPC, or death due to progression, whichever comes first.
Measured: From date of first dose of study drug up to the date of first documentation of disease progression or death due to progression, an average of 2 years.
Time to PSA progression (for prostate cancer only)
Time to PSA Progression will be calculated from the date of treatment initiation to the date of first documentation of PSA progression according to PCWG3 criteria.
Measured: From date of first dose of study drug up to the date of first documentation of PSA progression, an average of 1 year.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2019
- Study start25 Nov 2019
- Primary completion31 Mar 2023
- Study completion16 May 2024
Why it stopped: The study closure is related to sponsor decision to shift towards the clinical development of NMS-03305293 in combination in a broader range of indication and not based on emerging safety or efficacy concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced/Metastatic Solid TumorsStudies 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
- Sequential
- Model description
- Phase 1 Dose escalation part followed by a Dose Expansion part.
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nerviano Medical Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Valentina Guarneri, MD, Principal investigator, Istituto Oncologico Veneto IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04182516
- Sponsor's protocol ID
- PARPA-293-001
- Other IDs
- 2018-003918-40, 2018
- Status last verified
- Sep 2024
- First submitted
- 12 Nov 2019
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of NMS-03305293 in Adult Patients with Selected Advanced/Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT04182516
- Acronym / sponsor ID
- PARPA-293-001
- Conditions
- Advanced/Metastatic Solid Tumors
- Keywords
- HER2 negative breast cancer, Epithelial ovarian cancer, Castration-resistant prostate cancer (CRPC), Pancreatic cancer, BRCA1 Gene Mutation, BRCA2 Gene Mutation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study closure is related to sponsor decision to shift towards the clinical development of NMS-03305293 in combination in a broader range of indication and not based on emerging safety or efficacy concerns.
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Nerviano Medical SciencesIndustry (pharma, biotech, devices)
- Study start
- 25 Nov 2019 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 16 May 2024 (actual)
- First posted
- 2 Dec 2019 (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.
Phase I, first-in-human, open-label, multicenter, dose-escalation and dose expansion study with the aim of exploring safety, tolerability and preliminary antitumor activity of NMS-03305293 (a PARP inhibitor) as single agent in adult patients with selected advanced/metastatic, relapsed/refractory solid tumors who have exhausted standard treatment options or for whom standard therapy is considered unsuitable.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- Phase 1 Dose escalation part followed by a Dose Expansion part.
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Part | Experimental | Drug: NMS-03305293Patients with histologically confirmed diagnosis of locally advanced/metastatic HER2 negative breast cancer, epithelial ovarian cancer, castration-resistant prostate cancer (CRPC) or pancreatic cancer. |
| Dose Expansion Part - Epithelial Ovarian Cancer | Experimental | Drug: NMS-03305293Patients with gBRCA mutation and epithelial ovarian cancer. |
| Dose Expansion Part - Pretreated HER 2 Neg. Breast Cancer | Experimental | Drug: NMS-03305293Patients with gBRCA mutation and HER2 negative breast cancer previously treated with a PARP inhibitor. |
| Dose Expansion Part - No Pretreated HER 2 Neg. Breast Cancer | Experimental | Drug: NMS-03305293Patients with gBRCA mutation and HER2 negative breast cancer who have not received prior therapy with a PARP inhibitor. |
| Dose Expansion Part - CRPC | Experimental | Drug: NMS-03305293Patients with gBRCA mutation and castration-resistant prostate cancer (CRPC). |
| Dose Expansion Part - Pancreatic Cancer | Experimental | Drug: NMS-03305293Patients with gBRCA mutation and pancreatic cancer who have not received prior therapy with a PARP inhibitor. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Patients with histologically confirmed diagnosis of locally advanced/metastatic HER2 negative breast cancer, epithelial ovarian cancer, castration-resistant prostate cancer (CRPC) or pancreatic cancer. BRCA1 and BRCA2 mutation status is not required for enrollment in the Dose Escalation part, but enrichment with deleterious/pathogenic or likely pathogenic/suspected deleterious BRCA carriers will be attempted.
- Patients must have progressive disease defined by RECIST 1.1 following standard therapy or be unsuitable for standard therapy. For CRPC patients, disease progression at study entry is defined as one or more of the following three criteria (according to PCWG2):
- Male or female patients with age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
- Life expectancy of at least 3 months.
Key exclusion criteria (18 listed)
- Current enrollment in another therapeutic clinical trial.
- Prior malignancy except for any of the following:
- Patients with prior platinum therapy exposure who had evidence of disease progression during platinum treatment (refractory disease) and patients whose disease relapsed within 6 months of the last dose of prior adjuvant or neo-adjuvant platinum therapy.
- Patients who have received prior PARP inhibitors are excluded in the following two cohorts of the Dose Expansion part: HER2 negative breast cancer patients not treated with prior PARP inhibitors and the pancreatic cancer patients cohort. Previous treatment with PARP inhibitors is allowed in the dose escalation part and in the expansion cohorts of ovarian cancer patients and CRPC patients.
- Patients with known symptomatic brain metastases or leptomeningeal involvement. Patients with asymptomatic brain metastases or leptomeningeal involvement are excluded in the Dose Escalation Part only.
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 |
|---|---|---|
| NMS-03305293All patients will receive NMS-03305293 administered orally on Days 1-21 (schedule A) or Days 1-28 (schedule B) in repeated 4-week cycles. | Drug | Dose Escalation Part, Dose Expansion Part - CRPC, Dose Expansion Part - Epithelial Ovarian Cancer, Dose Expansion Part - No Pretreated HER 2 Neg. Breast Cancer, Dose Expansion Part - Pancreatic Cancer, Dose Expansion Part - Pretreated HER 2 Neg. Breast Cancer |
Primary outcome
Number of Participants with first-cycle dose limiting toxicity
Time frame: Time interval between the date of the first dose administration in Cycle 1 (each cycle is 28 days) and the date of the first dose administration in Cycle 2 which is expected to be 28 days or up to 42 days in case of dose delay due to toxicity
14 secondary outcomes
Number of participants with Adverse Events (AEs)
Time frame: From the Informed Consent signature to 28 days after the last dose of study treatment administration.
Maximum concentration (Cmax) of NMS-03305293 after single and multiple doses of drug
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Time to observed Cmax (Tmax) of NMS-033052293 after single and multiple doses of drug
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Area under the concentration-time curve to the last of measurable concentration (AUClast) of NMS-033052293 after single and repeated dose of drug.
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Terminal elimination half-life (t1/2) of NMS-033052293 after single and multiple doses of drug.
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Area under the plasma concentration vs. time curve to infinity (AUCinf) of NMS-033052293 after multiple doses of drug.
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Accumulation ratio (Rac) of NMS-033052293 after multiple doses of drug.
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Oral plasma clearance (CL/F) of NMS-033052293 after multiple doses of drug.
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Apparent volume of distribution (Vd/F) of NMS-033052293 after multiple doses of drug.
Time frame: Full PK : Schedule A, QD and BID dosing: Cycle 1, 2; Schedule B, QD and BID dosing: Cycle 1, 2 and 3. Sparse PK: Schedule A: and Schedule B Cycle 1, 2, 3 (last cycle and at each cycle from cycle 1 onwards).Cycle lenght is 4 weeks.
Renal clearance of NMS-033052293 after multiple doses of drug.
Time frame: Schedule A, QD and BID dosing: Cycle 1 (Day 1 and 21). ; Schedule B, QD and BID dosing: Cycle 1 (Day 1 and 28).Cycle lenght is 4 weeks.
Objective tumor response (OR)
Time frame: At baseline, every even cycle (Day 28), at the end of treatment and at follow-up, every 8 weeks, till disease progression, an average 18 months.
Progression Free Survival (PFS)
Time frame: From date of first dose of study drug up to the date of first documentation of disease progression or death due to any cause, whichever comes first, an average of 2 years.
Time To Progression (TTP)
Time frame: From date of first dose of study drug up to the date of first documentation of disease progression or death due to progression, an average of 2 years.
Time to PSA progression (for prostate cancer only)
Time frame: From date of first dose of study drug up to the date of first documentation of PSA progression, an average of 1 year.
Results and safety
The study was stopped early (reason given: The study closure is related to sponsor decision to shift towards the clinical development of NMS-03305293 in combination in a broader range of indication and not based on emerging safety or efficacy concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
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RecruitingPhase 1/2
Docetaxel and SX-682 in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma, Salivary Gland Carcinoma, and Advanced Prostate Cancer
Head and Neck Cancer, Head and Neck Squamous Cell Carcinoma
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
RecruitingPhase 1
A Study to Learn About the Study Medicine Called PF-08046876 in People With Advanced Solid Tumors
Advanced/Metastatic Solid Tumors, Bladder Cancer
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.
Valentina Guarneri, MD principal investigator
Istituto Oncologico Veneto IRCCS
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NMS-03305293 in people with Advanced/Metastatic Solid Tumors, run by Nerviano Medical Sciences at 10 sites in 5 countries.
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 26 inclusion and 18 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: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Bulgaria, Italy, China, United States, United Kingdom. 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 was stopped early (reason given: The study closure is related to sponsor decision to shift towards the clinical development of NMS-03305293 in combination in a broader range of indication and not based on emerging safety or efficacy concerns.). Results are not available in the source record.
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?
Number of Participants with first-cycle dose limiting toxicity (time frame: Time interval between the date of the first dose administration in Cycle 1 (each cycle is 28 days) and the date of the first dose administration in Cycle 2 which is expected to be 28 days or up to 42 days in case of dose delay due to toxicity). 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 19 Sep 2024.