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Trial record 1 of 1 for:    NCT02936323
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PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers

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ClinicalTrials.gov Identifier: NCT02936323
Recruitment Status : Completed
First Posted : October 18, 2016
Last Update Posted : March 11, 2021
Sponsor:
Information provided by (Responsible Party):
Tarveda Therapeutics

Tracking Information
First Submitted Date  ICMJE October 13, 2016
First Posted Date  ICMJE October 18, 2016
Last Update Posted Date March 11, 2021
Actual Study Start Date  ICMJE December 8, 2016
Actual Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Phase 1: Maximum tolerated dose (MTD) and recommended Phase 2a dose (RP2D). [ Time Frame: From date of first treatment/trial entry until 28 days after last treatment, estimated 12 months ]
    Determine the MTD and the RP2D by assessing treatment related adverse events.
  • Phase 2a: Efficacy of PEN-221 in gastrointestinal mid-gut NETs and pancreatic NETs as determined by RECIST 1.1 [ Time Frame: Up to 36 months ]
    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.
  • Phase 2a: Efficacy of PEN-221 in Small Cell Lung Cancer (SCLC) as determined by RECIST 1.1 [ Time Frame: Up to 36 months ]
    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, along with duration of response (DOR).
Original Primary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
Treatment related adverse events [ Time Frame: From date of first treatment/trial entry until 28 days after last treatment, estimated 12 months ]
Treatment related adverse events are assessed using CTCAE criteria.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2019)
  • Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) [ Time Frame: From date of first treatment/trial entry until 28 days after last treatment, estimated 12 months ]
    Characterize the safety and tolerability of PEN-221 by assessing treatment related adverse events.
  • Maximum concentration (Cmax) of PEN-221, DM1, and peptide from the serum [ Time Frame: Up to 2 months ]
    Characterize the maximum concentration of PEN-221, DM1, and peptide in circulating blood
  • Area under the curve (AUC) of PEN-221, DM1, and peptide from the serum [ Time Frame: Up to 2 months ]
    Characterize the AUC of PEN-221, DM1, and peptide in circulating blood
  • Half-life (t1/2) of PEN-221, DM1, and peptide from the serum [ Time Frame: Up to 2 months ]
    Characterize the half-life (t1/2) of PEN-221, DM1, and peptide in circulating blood
  • Phase 1: Anti-tumor activity of PEN-221 [ 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 (estimated 12 months) ]
    Assess the potential of preliminary anti-tumor activity of PEN-221 using tumor response criteria as defined by RECIST 1.1 and DOR.
  • Phase 2a: Maximum tolerated dose (MTD) [ Time Frame: From date of first treatment/trial entry until 28 days after last treatment, estimated 12 months ]
    Confirm the MTD identified during Phase 1 and further investigate the safety and tolerability of the recommended phase 2a dose (RP2D).
  • 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 (estimated) 36 months ]
    Time from first PEN-221 dose to date of first documented disease progression per RECIST 1.1.
  • Phase 2a: Overall Survival (OS) [ Time Frame: From date of first treatment/trial entry until the date of death from any cause, assessed up to (estimated) 36 months ]
    The time from first PEN-221 dose to the date of death due to any cause.
  • Phase 2a: ORR for gastrointestinal mid-gut NETs and pancreatic NETs [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to (estimated) 36 months ]
    Evaluate ORR for gastrointestinal mid-gut NETs and pancreatic NETs.
  • Phase 2a: DOR for gastrointestinal mid-gut NETs and pancreatic NETs [ Time Frame: From the date of first treatment through the date of first documented progression, assessed up to (estimated) 36 months ]
    Evaluate DOR for gastrointestinal mid-gut NETs and pancreatic NETs.
  • Anti-PEN-221 antibodies [ Time Frame: Baseline and every 6 weeks up to end of treatment (estimated 12 months) ]
    Assess the potential of PEN-221 to induce anti-PEN-221 antibodies in the serum.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2016)
  • Maximum concentration of PEN-221 and its metabolites (Cmax) [ Time Frame: 2 months ]
    Maximum concentration of PEN-221 concentration in circulating blood
  • Area under the curve (AUC) of PEN-221 and its metabolites [ Time Frame: 2 months ]
    Area under PEN-221 concentration v time curve in circulating blood
  • Half-life (t1/2) of PEN-221 and its metabolites [ Time Frame: 2 months ]
    Half life of PEN-221 concentration in circulating blood
  • Tumor responses using RECIST criteria [ Time Frame: 2 months ]
    Size of tumors by CT or MRI (RECIST)
  • Radiographic progression free survival [ Time Frame: From date of first treatment/trial entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to (estimated) 36 months ]
    Size of tumors by CT or MRI (RECIST)
  • Overall survival [ Time Frame: From date of first treatment/trial entry until the date of date of death from any cause, assessed up to (estimated) 36 months ]
    Time to death
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers
Official Title  ICMJE 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
Brief 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.
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Neuroendocrine Tumors
  • Carcinoma, Small Cell Lung
  • Neuroendocrine Carcinoma
Intervention  ICMJE Drug: PEN-221
Administration of PEN-221 once every three weeks
Study Arms  ICMJE Experimental: PEN-221
intravenous administration of PEN-221
Intervention: Drug: PEN-221
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 9, 2021)
89
Original Estimated Enrollment  ICMJE
 (submitted: October 14, 2016)
120
Actual Study Completion Date  ICMJE February 25, 2021
Actual Primary Completion Date July 31, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

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.

Exclusion Criteria:

  • 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
  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02936323
Other Study ID Numbers  ICMJE PEN-221-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Tarveda Therapeutics
Study Sponsor  ICMJE Tarveda Therapeutics
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chief Medical Officer Tarveda Therapeutics
PRS Account Tarveda Therapeutics
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP