Clinical Trial - NCT02936323

PEN-221 in Somatostatin Receptor 2 Expressing Advanced Cancers Including Neuroendocrine and Small Cell Lung Cancers

Recruiting

Sponsor: Tarveda Therapeutics

Collaborators:

Information provided by (Responsible party): Sponsor

ClinicalTrials.gov Identifier: NCT02936323

Protocol Info

Short Description: PEN-221 IN RECEPTOR 2 EXPRESSING ADVANCED CANCERS
Long Description: 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.
MGH Status: Open
Sponsor: Tarveda Therapeutics
Disease Program: GI

Next Steps


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Purpose

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.
Condition Title Intervention Phase
Neuroendocrine Tumors Carcinoma, Small Cell Lung Neuroendocrine Carcinoma PEN-221 Phase 1/Phase 2
Study Type Interventional
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

Primary Outcome Measures

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Phase 2a: Efficacy of PEN-221 in Small Cell Lung Cancer (SCLC) as determined by RECIST 1.1 [Time Frame: Up to 36 months] [Designated as safety issue: ]


Secondary Outcome Measures

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] [Designated as safety issue: ]

Maximum concentration (Cmax) of PEN-221, DM1, and peptide from the serum [Time Frame: Up to 2 months] [Designated as safety issue: ]

Area under the curve (AUC) of PEN-221, DM1, and peptide from the serum [Time Frame: Up to 2 months] [Designated as safety issue: ]

Half-life (t1/2) of PEN-221, DM1, and peptide from the serum [Time Frame: Up to 2 months] [Designated as safety issue: ]

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)] [Designated as safety issue: ]

Phase 2a: Maximum tolerated dose (MTD) [Time Frame: From date of first treatment/trial entry until 28 days after last treatment, estimated 12 months] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

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] [Designated as safety issue: ]

Anti-PEN-221 antibodies [Time Frame: Baseline and every 6 weeks up to end of treatment (estimated 12 months)] [Designated as safety issue: ]

Estimated Enrollment: 90
Study Start Date: December 2016
Estimated Study Completion Date: December 2019
Estimated Primary Completion Date: June 2019
Arms Assigned Interventions

Experimental:PEN-221

intravenous administration of PEN-221
Drug:PEN-221
Administration of PEN-221 once every three weeks

Eligibility

Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT02936323

Locations

  • United States, Massachusetts
    • Massachusetts General Hospital Boston, Massachusetts, United States, 02114
    • Beth Israel Deaconess Medical Center Boston, Massachusetts, United States, 02215
    • Dana-Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, New York
    • Columbia University Medical Center/ NY Presbyterian Manhattan, New York, United States, 10032
  • United States, Ohio
    • University Hospitals Cleveland Medical Center Cleveland, Ohio, United States, 44106
  • United States, Tennessee
    • Sarah Cannon Research Institute/Tennessee Oncology Nashville, Tennessee, United States, 37203
  • United States, Texas
    • MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United Kingdom,
    • University College London London, , United Kingdom,
    • The Christie NHS Trust Manchester, , United Kingdom,

Sponsors and Collaborators

Tarveda Therapeutics

More Information

No publications provided

Responsible Party: Sponsor
ClinicalTrials.gov Identifier: NCT02936323
Other Study ID Numbers:
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Tarveda Therapeutics:

SCLC small cell lung cancer

pancreatic neuroendocrine NET

GI neuroendocrine NET

Additional relevant MeSH terms:

Carcinoma

Lung Neoplasms

Small Cell Lung Carcinoma

Neuroendocrine Tumors

Carcinoma, Neuroendocrine

Carcinoma, Small Cell

Somatostatin

Next Steps


If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.







ClinicalTrials.gov processed this data on August 15, 2019