Neuroendocrine TumorsPhase 1/2NCT02936323
PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers
A Phase 1/2 study testing PEN-221 in people with Neuroendocrine Tumors and Carcinoma, Small Cell Lung, run by Tarveda Therapeutics at 13 sites in 2 countries.
Trial summary
Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neuroendocrine Tumors, Carcinoma, Small Cell Lung, Neuroendocrine Carcinoma
- What is being tested?
- PEN-221
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 89 participants
- Where
- 13 sitesin 2 countries
- Study dates
- 8 Dec 2016to 25 Feb 2021
- Phase
- Phase 1/2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- M/F at least 18 years old
- ECOG performance status 0 or 1
- Adequate bone marrow, liver, and kidney function within 2 weeks prior to first dose
- Serum potassium, calcium, magnesium, phosphorus within normal limits (may be supplemented)
- Adequate birth control
- Somatostatin receptor 2 positive tumor as assessed at pre-screening or within 180 d of first drug dose using indium SPECT or gallium PET
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- Patients in Phase 1 must have a histologically or cytologically-confirmed solid tumor in 1 of the following categories:
- Advanced small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC) of lung progressed after at least 1 line of anticancer chemotherapy
- Advanced low or intermediate grade gastroenteropancreatic or lung or thymus neuroendocrine tumor (NET), or NET of unknown primary, progressed after at least 1 line of anticancer therapy (unless no standard treatments available or such treatments are deemed not appropriate)
- Advanced paraganglioma, pheochromocytoma, medullary thyroid carcinoma, Merkel cell carcinoma, or high grade extrapulmonary neuroendocrine carcinoma having progressed after 1 or more lines of anticancer chemotherapy (unless no standard treatments available or such treatments are deemed not appropriate)
- For patients enrolling once escalation is complete (Phase 2a), disease must be measurable per RECIST 1.1 criteria with last imaging performed within 28 days prior to first drug dose
- In addition to the criterion listed above, Patients in Phase 2a must have a histologically- or cytologically-confirmed, advanced or metastatic solid tumor, in 1 of the following categories: disease history specified in one of the criteria listed below:
- Well differentiated, low or intermediate grade, gastrointestinal mid-gut (arising from the lower jejunum, ileum, appendix, cecum, and proximal colon) NET with documented disease progression within 6 months prior to start of study treatment and evidence of radiographic disease progression based on scans performed not more than 15 months apart. Patients may have received 1 or more prior lines of anticancer therapy, such as somatostatin analogues, targeted agents, or liver-directed intra-arterial therapy, but are NOT eligible if they have received prior systemic cytotoxic chemotherapy.
- Well differentiated, low or intermediate grade, pancreatic NET with documented disease progression within 6 months prior to start of study treatment and evidence of radiographic disease progression based on scans performed not more than 15 months apart. Patients may have received 1 or more prior lines of anticancer therapy, such as somatostatin analogues, targeted agents, or liver-directed intra-arterial therapy, and up to 1 prior line of systemic cytotoxic chemotherapy, but are NOT eligible if they have received more than 1 prior line of systemic cytotoxic chemotherapy or if they have received prior peptide receptor radionuclide therapy (PRRT)
- SCLC after having received up to three prior lines of anticancer therapy.
Who cannot join
- Treatment with anticancer therapy or investigational drug or device within 3 wk (6 wk for nitrosureas or mitomycin C) or 5 half-lives of agent, whichever is shorter, prior to first PEN-221 drug dose, and any drug-related toxicities must have recovered to grade 1 or less
- Any other malignancy known to be active or treated within 3 years of start of screening, except cervical intra-epithelial neoplasia, superficial (non-invasive) bladder cancer, and non-melanoma skin cancer
- Cardiac criteria such as unstable angina, myocardial infarction within 6 months of screening, NY Heart Association Class 1 or 2 heart failure, QTc greater than 470 msec, congenital long Qt syndrome, symptomatic orthostatic hypotension within 6 months of screening, uncontrolled hypertension, or clinically important abnormalities in heart rhythm, conduction, morphology of resting ECG
- Stroke or transient ischemic attack within 6 months of screening
- Peripheral neuropathy greater than grade 1
- Requirement for medication with strong CYP3A4 inhibitor
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- History of leptomeningeal disease or spinal cord compression
- Brain metastases unless asymptomatic on a stable low dose of steroids. Patients with SCLC or LCNEC of lung only must have CT or MRI of brain during screening, and if metastases found, must have radiotherapy with 14 day washout or stereotactic radiotherapy or radio surgery with 7 day washout prior to first drug dose.
- Major surgery within 28 days of first drug dose
- Female who is pregnant or breast feeding
- Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver transplant, active infection with hepatitis B or C, or HIV
- Hypersensitivity or anaphylactic reaction to any somatostatin analog or to maytansinoids
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Florida Cancer Specialists South
Fort Myers, Florida, 33901
MD Anderson Cancer Center
Houston, Texas, 77030
Columbia University Medical Center/ NY Presbyterian
Manhattan, New York, 10032
Sarah Cannon Research Institute/Tennessee Oncology
Nashville, Tennessee, 37203
Florida Cancer Specialists North
St. Petersburg, Florida, 33705
United Kingdom3 sites
University College London
London
The Christie NHS Trust
Manchester
Southampton General Hospital
Southampton
About this study
Official title: A Phase 1/2a, Open-label Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of PEN-221 in Patients With Somatostatin Receptor 2 Expressing Advanced Cancers, Including Gastroenteropancreatic or Lung or Thymus or Other Neuroendocrine Tumors or Small Cell Lung Cancer or Large Cell Neuroendocrine Carcinoma of the Lung
Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung.
Read the detailed description
Protocol PEN-221-001 will first enroll patients into a dose escalation phase, where a Bayesian logistic regression model, guided by the escalation with overdose control principle and overseen by a safety review committee, will be used to make dose recommendations and estimate the maximum tolerated dose (MTD).
Once the MTD has been confirmed, remaining patients will be enrolled into a full expansion phase to assess PEN-221 efficacy in patients with gastrointestinal mid-gut neuroendocrine tumors or pancreatic neuroendocrine tumors or small cell lung cancer.
- Being tested
- PEN-221
- Keywords
- SCLC small cell lung cancer, pancreatic neuroendocrine NET, GI neuroendocrine NET
- Medical subject headings
- Neuroendocrine Tumors, Small Cell Lung Carcinoma, Carcinoma, Neuroendocrine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PEN-221Drug
PEN-221 administered IV over 1 hour on an every 3-week cycle (21 days +/- 2 days) starting dose of 1 mg with each subsequent cohort increased starting dose level until MTD is reached.
PEN-221Drug
PEN-221 administered IV over 1 hour on an every 3-week cycle (21 days +/- 2 days) starting dose at recommended Phase 2a dose established in Phase 1.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1: Dose Escalation | Experimental | Cohort 1 will consist of two (2) participants who will receive PEN-221 at the starting dose of 1.0 mg. The first participant will be followed for at least 7 days for safety and dose limiting toxicity (DLT). If PEN-221 is tolerated, the second participant will be enrolled into the cohort. The two (2) participants will be followed for safety and DLTs for at least a 4-week observation period. The Safety Review Committee (SRC) will determine the initiation of cohort 2.
Cohort 2 and each subsequent dose escalation cohort will consist of 3 to 6 participants who will be treated at each dose level of PEN-221 as determined by the SRC and will be followed for safety and DLTs for at least a 3-week observation period. Each dose escalation level and cohort initiation will be determined by the SRC.
Dose escalation will continue until the Maximum Tolerated Dose (MTD) of PEN-221 is determined and the Recommended Phase 2a Dose (RP2D) is established by the SRC. Receives: Drug: PEN-221 |
| Phase 2a: Dose Expansion (GI mid-gut NET) | Experimental | Gastrointestinal mid-gut NET Cohort Receives: Drug: PEN-221 |
| Phase 2a: Dose Expansion (PNET) | Experimental | Pancreatic NET Cohort Receives: Drug: PEN-221 |
| Phase 2a: Dose Expansion (SCLC) | Experimental | Small Cell Lung Cancer Cohort Receives: Drug: PEN-221 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Maximum Tolerated Dose of PEN-221 and Recommended Phase 2a Dose (RP2D)
MTD was determined by testing increasing doses up to 25 mg flat dose IV over 1 hour on an every 3 week cycle on dose escalation cohorts 1 to 7 with 2 participants in cohort 1 and 3-6 participants each in cohorts 2-7. The MTD was defined as the highest drug dosage not causing a Dose Limiting Toxicity (DLT) in > 33% of the treated participants during the first cycle of treatment. DLTs were defined as any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.03 occurring within the first 4 weeks for cohort 1 and within 3 weeks for each subsequent cohort that was not related to underlying disease, disease progression, intercurrent illness, or concomitant medications. The RP2D was established by achieving the Maximum Tolerated Dose (MTD). The RP2D may be equal to or below the MTD.
Measured: Up to 4 weeks in the first cohort and up to 3 weeks for each subsequent cohort
Phase 1: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
DLTs were defined as any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.03 occurring within the first 4 weeks for cohort 1 and within 3 weeks for each subsequent cohort that was not related to underlying disease, disease progression, intercurrent illness, or concomitant medications. Grade 3 is a severe AE and Grade 4 is a life-threatening or disabling AE. DLTs were collected to determine the Maximum-Tolerated Dose (MTD), which is defined as the dose level below the dose at which > 33% of participants experienced a DLT during the first cycle of treatment.
Measured: Up to 4 weeks in the first cohort and up to 3 weeks for each subsequent cohort
Phase 2a: Percentage of Gastrointestinal Mid-gut NETs and Pancreatic NETs Participants Who Achieved Clinical Benefit as Determined by RECIST 1.1
Efficacy of PEN-221 in gastrointestinal mid-gut NETs and pancreatic NETs using clinical benefit rate (CBR) defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1 using the investigator assessment.
Measured: Baseline and every 9 weeks up to time of disease progression (per RECIST 1.1) or death, up to data cut-off (31 Jul 2020).
Phase 2a: Number of Small Cell Lung Cancer (SCLC) Participants Who Achieved an Objective Response of Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1.
Efficacy of PEN-221 in Small Cell Lung Cancer (SCLC) using objective response rate (ORR) as defined as the best overall response of CR or PR using tumor response criteria defined by RECIST 1.1.
Measured: Baseline and every 6 weeks up to time of disease progression (per RECIST 1.1) or death, up to data cut-off (31 Jul 2020).
Phase 2a: Duration of Response (DOR) for Small Cell Lung Cancer (SCLC)
Duration of Response (DOR) is defined as the time from the first documented response (CR or PR), as assessed by the investigator, to the date of first documented disease progression or death due to underlying cancer. If patient did not progress or die before the data cutoff date (31-July-2020), DOR was censored at the date of last adequate tumor assessment.
Measured: From the date of first treatment through the date of first documented progression, assessed up to data cut-off (31 Jul 2020).
Secondary outcomes (11)
Number of Study Participants Who Experienced Treatment-Emergent Adverse Events
Phase 1 and Phase 2a participants who experienced any Treatment-Emergent Adverse Event (TEAE) to determine the safety and tolerability of PEN-221. TEAEs are any AE that occurred after first dose of study drug through 28 days after the last dose of study drug, any event considered study drug related regardless of start date of the event, or any event that was present at baseline but worsened in intensity or was subsequently considered study drug related by the Investigator. Phase 2a TEAEs were collected for reporting in the BSA dosing format only.
Measured: From date of first treatment/trial entry until 28 days after last treatment for each participant, up to data cut-off (31 Jul 2020).
Maximum Concentration (Cmax) of PEN-221, DM1, and Peptide
Blood samples were obtained and plasma concentrations were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Phase 2a data were collected for reporting in the BSA dosing format only.
Measured: Phase 1: Day 1 of Cycles 1 and 3 pre-start of infusion (SOI), at 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-start of infusion. Phase 2a: Day 1 Cycle 1 pre-start of infusion, at 0.5,1, 1.5, 2, 4, 6, 8, 24 hours post-SOI; once at Day 8 Cycle 1.
Area Under the Curve (AUC) of PEN-221, DM1, and Peptide
Blood samples were obtained and plasma concentrations were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Phase 2a data were collected for reporting in the BSA dosing format only.
Measured: Phase 1: Day 1 of Cycles 1 and 3 pre-start of infusion (SOI), at 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-start of infusion. Phase 2a: Day 1 Cycle 1 pre-start of infusion, at 0.5,1, 1.5, 2, 4, 6, 8, 24 hours post-SOI; once at Day 8 Cycle 1.
Half-life (t1/2) of PEN-221, DM1, and Peptide
Blood samples were obtained and plasma concentrations were determined using validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. Phase 2a data collected for reporting in the BSA dosing format only.
Measured: Phase 1: Day 1 of Cycles 1 and 3 pre-start of infusion (SOI), at 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-start of infusion. Phase 2a: Day 1 Cycle 1 pre-start of infusion, at 0.5,1, 1.5, 2, 4, 6, 8, 24 hours post-SOI; once at Day 8 Cycle 1.
Phase 1: Number of Participants With a Best Response of an Objective Response, Stable Disease, or Progressive Disease.
Assess the potential of preliminary anti-tumor activity of PEN-221 using tumor response criteria as defined by RECIST 1.1.
Measured: Baseline, every 6 or 9 weeks depending on the tumor type, up to time of disease progression (per RECIST 1.1) or death, up to data cut-off (31 Jul 2020).
Phase 2a: Maximum Tolerated Dose (MTD) and Recommended Phase 2a Dose (RP2D) Based on Body Surface Area
Confirm the MTD identified during the dose-escalation phase and further investigate the safety and tolerability of the RP2D and schedule of PEN-221. Initial Phase 2a PEN-221 start dose at Phase 1 MTD and RP2D was determined at 18 mg flat dose. The MTD was defined as the highest drug dosage not causing a Dose Limiting Toxicity (DLT) in > 33% of the treated participants during the first cycle of treatment. DLTs were defined as any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.03 occurring within the first 4 weeks for cohort 1 and within 3 weeks for each subsequent cohort that was not related to underlying disease, disease progression, intercurrent illness, or concomitant medications. The RP2D was established by achieving the Maximum Tolerated Dose (MTD). The RP2D may be equal to or below the MTD.
Measured: From date of first treatment/trial entry until 28 days after last treatment for each Phase 2a participant, up to data cut-off (31 Jul 2020)
Phase 2a: Progression Free Survival (PFS)
Progression free survival (PFS) is defined as the time from the date of first dose of PEN-221 to the date of first documented disease progression per RECIST 1.1, or death due to any cause. If a participant had not progressed or died before the analysis cutoff date (31 Jul 2020), PFS was censored at the date of last adequate tumor assessment. Results based on Kaplan-Meier estimates.
Measured: From date of first treatment/trial entry until first documented progression or date of death from any cause, whichever came first, assessed up to data cutoff of 31 Jul 2020
Phase 2a: Overall Survival (OS)
Overall survival (OS) was defined as the time from the first dose of PEN-221 to the date of death due to any cause. If the participant had not died before data lock (31 Jul 2020), OS was censored at the date of last contact.
Measured: For each GI mid-gut NET, PNET, and SCLC, from date of first treatment/trial entry until the date of death from any cause, assessed up to data cutoff of 31 Jul 2020
Phase 2a: ORR for Gastrointestinal Mid-gut NETs (GI Mid-gut NET) and Pancreatic NETs (PNET)
The Objective Response Rate (ORR) is defined as the proportion of patients with a best overall CR or PR as defined by RECIST 1.1 using the investigator assessment captured on the electronic Case Report Form.
Measured: For each GI mid-gut NET and PNET participant from the date of first treatment through the date of first documented progression, assessed up to data cutoff 31 Jul 2020
Phase 2a: Duration of Response (DOR) for Gastrointestinal Mid-gut NETs (GI Mid-gut NET) and Pancreatic NETs (PNET)
Duration of Response (DOR) is defined as the time from the first documented response (CR or PR), as assessed by the investigator, to the date of first documented disease progression or death due to underlying cancer. If a patient did not progress or die before the data cutoff date (31 Jul 2020), DOR was censored at the date of last adequate tumor assessment.
Measured: For each GI mid-gut NET and PNET participant, from the date of first treatment through the date of first documented progression, assessed up to data cutoff (31 Jul 2020)
Anti-PEN-221 Antibodies (ADA)
Plasma Samples Using an Electrochemiluminescent Method for the Detection of Anti-PEN-221 Antibodies in Human Serum.
Measured: Baseline and every 6 weeks up to end of treatment for each patient.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2016 (estimated)
- Study start8 Dec 2016
- Primary completion31 Jul 2020
- Study completion25 Feb 2021
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 Neuroendocrine 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tarveda Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer, Study director, Tarveda Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02936323
- Sponsor's protocol ID
- PEN-221-001
- Status last verified
- Nov 2021
- First submitted
- 13 Oct 2016
- Last updated
- 14 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- 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 14 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2a, Open-label Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of PEN-221 in Patients With Somatostatin Receptor 2 Expressing Advanced Cancers, Including Gastroenteropancreatic or Lung or Thymus or Other Neuroendocrine Tumors or Small Cell Lung Cancer or Large Cell Neuroendocrine Carcinoma of the Lung
- ClinicalTrials.gov ID
- NCT02936323
- Acronym / sponsor ID
- PEN-221-001
- Keywords
- SCLC small cell lung cancer, pancreatic neuroendocrine NET, GI neuroendocrine NET
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Tarveda TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 8 Dec 2016 (actual)
- Primary completion
- 31 Jul 2020 (actual)
- Study completion
- 25 Feb 2021 (actual)
- First posted
- 18 Oct 2016 (estimated)
- Results
- Posted 14 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Protocol PEN-221-001 is an open-label, multicenter Phase 1/2a study evaluating PEN-221 in patients with SSTR2 expressing advanced gastroenteropancreatic (GEP) or lung or thymus or other neuroendocrine tumors or small cell lung cancer or large cell neuroendocrine carcinoma of the lung.
Detailed description
Protocol PEN-221-001 will first enroll patients into a dose escalation phase, where a Bayesian logistic regression model, guided by the escalation with overdose control principle and overseen by a safety review committee, will be used to make dose recommendations and estimate the maximum tolerated dose (MTD).
Once the MTD has been confirmed, remaining patients will be enrolled into a full expansion phase to assess PEN-221 efficacy in patients with gastrointestinal mid-gut neuroendocrine tumors or pancreatic neuroendocrine tumors or small cell lung cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Phase 1: Dose Escalation | Experimental | Drug: PEN-221Cohort 1 will consist of two (2) participants who will receive PEN-221 at the starting dose of 1.0 mg. The first participant will be followed for at least 7 days for safety and dose limiting toxicity (DLT). If PEN-221 is tolerated, the second participant will be enrolled into the cohort. The two (2) participants will be followed for safety and DLTs for at least a 4-week observation period. The Safety Review Committee (SRC) will determine the initiation of cohort 2. Cohort 2 and each subsequent dose escalation cohort will consist of 3 to 6 participants who will be treated at each dose level of PEN-221 as determined by the SRC and will be followed for safety and DLTs for at least a 3-week observation period. Each dose escalation level and cohort initiation will be determined by the SRC. Dose escalation will continue until the Maximum Tolerated Dose (MTD) of PEN-221 is determined and the Recommended Phase 2a Dose (RP2D) is established by the SRC. |
| Phase 2a: Dose Expansion (GI mid-gut NET) | Experimental | Drug: PEN-221Gastrointestinal mid-gut NET Cohort |
| Phase 2a: Dose Expansion (PNET) | Experimental | Drug: PEN-221Pancreatic NET Cohort |
| Phase 2a: Dose Expansion (SCLC) | Experimental | Drug: PEN-221Small Cell Lung Cancer Cohort |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- M/F at least 18 years old
- ECOG performance status 0 or 1
- Adequate bone marrow, liver, and kidney function within 2 weeks prior to first dose
- Serum potassium, calcium, magnesium, phosphorus within normal limits (may be supplemented)
- Adequate birth control
Key exclusion criteria (12 listed)
- Treatment with anticancer therapy or investigational drug or device within 3 wk (6 wk for nitrosureas or mitomycin C) or 5 half-lives of agent, whichever is shorter, prior to first PEN-221 drug dose, and any drug-related toxicities must have recovered to grade 1 or less
- Any other malignancy known to be active or treated within 3 years of start of screening, except cervical intra-epithelial neoplasia, superficial (non-invasive) bladder cancer, and non-melanoma skin cancer
- Cardiac criteria such as unstable angina, myocardial infarction within 6 months of screening, NY Heart Association Class 1 or 2 heart failure, QTc greater than 470 msec, congenital long Qt syndrome, symptomatic orthostatic hypotension within 6 months of screening, uncontrolled hypertension, or clinically important abnormalities in heart rhythm, conduction, morphology of resting ECG
- Stroke or transient ischemic attack within 6 months of screening
- Peripheral neuropathy greater than grade 1
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 |
|---|---|---|
| PEN-221PEN-221 administered IV over 1 hour on an every 3-week cycle (21 days +/- 2 days) starting dose of 1 mg with each subsequent cohort increased starting dose level until MTD is reached. | Drug | Phase 1: Dose Escalation |
| PEN-221PEN-221 administered IV over 1 hour on an every 3-week cycle (21 days +/- 2 days) starting dose at recommended Phase 2a dose established in Phase 1. | Drug | Phase 2a: Dose Expansion (GI mid-gut NET), Phase 2a: Dose Expansion (PNET), Phase 2a: Dose Expansion (SCLC) |
Primary outcome
Phase 1: Maximum Tolerated Dose of PEN-221 and Recommended Phase 2a Dose (RP2D)
Time frame: Up to 4 weeks in the first cohort and up to 3 weeks for each subsequent cohort
MTD was determined by testing increasing doses up to 25 mg flat dose IV over 1 hour on an every 3 week cycle on dose escalation cohorts 1 to 7 with 2 participants in cohort 1 and 3-6 participants each in cohorts 2-7. The MTD was defined as the highest drug dosage not causing a Dose Limiting Toxicity (DLT) in > 33% of the treated participants during the first cycle of treatment. DLTs were defined as any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.03 occurring within the first 4 weeks for cohort 1 and within 3 weeks for each subsequent cohort that was not related to underlying disease, disease progression, intercurrent illness, or concomitant medications. The RP2D was established by achieving the Maximum Tolerated Dose (MTD). The RP2D may be equal to or below the MTD.
Phase 1: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: Up to 4 weeks in the first cohort and up to 3 weeks for each subsequent cohort
DLTs were defined as any Grade 3 or 4 adverse event (AE) using the Common Terminology Criteria for Adverse Events Version 4.03 occurring within the first 4 weeks for cohort 1 and within 3 weeks for each subsequent cohort that was not related to underlying disease, disease progression, intercurrent illness, or concomitant medications. Grade 3 is a severe AE and Grade 4 is a life-threatening or disabling AE. DLTs were collected to determine the Maximum-Tolerated Dose (MTD), which is defined as the dose level below the dose at which > 33% of participants experienced a DLT during the first cycle of treatment.
Phase 2a: Percentage of Gastrointestinal Mid-gut NETs and Pancreatic NETs Participants Who Achieved Clinical Benefit as Determined by RECIST 1.1
Time frame: Baseline and every 9 weeks up to time of disease progression (per RECIST 1.1) or death, up to data cut-off (31 Jul 2020).
Efficacy of PEN-221 in gastrointestinal mid-gut NETs and pancreatic NETs using clinical benefit rate (CBR) defined as the best overall response of complete response (CR), partial response (PR), or stable disease (SD) according to RECIST 1.1 using the investigator assessment.
Phase 2a: Number of Small Cell Lung Cancer (SCLC) Participants Who Achieved an Objective Response of Complete Response (CR) or Partial Response (PR) as Defined by RECIST 1.1.
Time frame: Baseline and every 6 weeks up to time of disease progression (per RECIST 1.1) or death, up to data cut-off (31 Jul 2020).
Efficacy of PEN-221 in Small Cell Lung Cancer (SCLC) using objective response rate (ORR) as defined as the best overall response of CR or PR using tumor response criteria defined by RECIST 1.1.
Phase 2a: Duration of Response (DOR) for Small Cell Lung Cancer (SCLC)
Time frame: From the date of first treatment through the date of first documented progression, assessed up to data cut-off (31 Jul 2020).
Duration of Response (DOR) is defined as the time from the first documented response (CR or PR), as assessed by the investigator, to the date of first documented disease progression or death due to underlying cancer. If patient did not progress or die before the data cutoff date (31-July-2020), DOR was censored at the date of last adequate tumor assessment.
11 secondary outcomes
Number of Study Participants Who Experienced Treatment-Emergent Adverse Events
Time frame: From date of first treatment/trial entry until 28 days after last treatment for each participant, up to data cut-off (31 Jul 2020).
Maximum Concentration (Cmax) of PEN-221, DM1, and Peptide
Time frame: Phase 1: Day 1 of Cycles 1 and 3 pre-start of infusion (SOI), at 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-start of infusion. Phase 2a: Day 1 Cycle 1 pre-start of infusion, at 0.5,1, 1.5, 2, 4, 6, 8, 24 hours post-SOI; once at Day 8 Cycle 1.
Area Under the Curve (AUC) of PEN-221, DM1, and Peptide
Time frame: Phase 1: Day 1 of Cycles 1 and 3 pre-start of infusion (SOI), at 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-start of infusion. Phase 2a: Day 1 Cycle 1 pre-start of infusion, at 0.5,1, 1.5, 2, 4, 6, 8, 24 hours post-SOI; once at Day 8 Cycle 1.
Half-life (t1/2) of PEN-221, DM1, and Peptide
Time frame: Phase 1: Day 1 of Cycles 1 and 3 pre-start of infusion (SOI), at 0.5, 1, 1.5, 2, 4, 6, 8, 10 hours post-start of infusion. Phase 2a: Day 1 Cycle 1 pre-start of infusion, at 0.5,1, 1.5, 2, 4, 6, 8, 24 hours post-SOI; once at Day 8 Cycle 1.
Phase 1: Number of Participants With a Best Response of an Objective Response, Stable Disease, or Progressive Disease.
Time frame: Baseline, every 6 or 9 weeks depending on the tumor type, up to time of disease progression (per RECIST 1.1) or death, up to data cut-off (31 Jul 2020).
Phase 2a: Maximum Tolerated Dose (MTD) and Recommended Phase 2a Dose (RP2D) Based on Body Surface Area
Time frame: From date of first treatment/trial entry until 28 days after last treatment for each Phase 2a participant, up to data cut-off (31 Jul 2020)
Phase 2a: Progression Free Survival (PFS)
Time frame: From date of first treatment/trial entry until first documented progression or date of death from any cause, whichever came first, assessed up to data cutoff of 31 Jul 2020
Phase 2a: Overall Survival (OS)
Time frame: For each GI mid-gut NET, PNET, and SCLC, from date of first treatment/trial entry until the date of death from any cause, assessed up to data cutoff of 31 Jul 2020
Phase 2a: ORR for Gastrointestinal Mid-gut NETs (GI Mid-gut NET) and Pancreatic NETs (PNET)
Time frame: For each GI mid-gut NET and PNET participant from the date of first treatment through the date of first documented progression, assessed up to data cutoff 31 Jul 2020
Phase 2a: Duration of Response (DOR) for Gastrointestinal Mid-gut NETs (GI Mid-gut NET) and Pancreatic NETs (PNET)
Time frame: For each GI mid-gut NET and PNET participant, from the date of first treatment through the date of first documented progression, assessed up to data cutoff (31 Jul 2020)
Anti-PEN-221 Antibodies (ADA)
Time frame: Baseline and every 6 weeks up to end of treatment for each patient.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Chief Medical Officer study director
Tarveda Therapeutics
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PEN-221 in people with Neuroendocrine Tumors and Carcinoma, Small Cell Lung, run by Tarveda Therapeutics at 13 sites in 2 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 15 inclusion and 12 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 14 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in 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 combined 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.
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 14 Dec 2021). 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?
Phase 1: Maximum Tolerated Dose of PEN-221 and Recommended Phase 2a Dose (RP2D) (time frame: Up to 4 weeks in the first cohort and up to 3 weeks for each subsequent cohort). The study lists 5 primary outcomes in all. 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 Dec 2021.