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

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Neuroendocrine Tumors; Carcinoma, Small Cell Lung; Neuroendocrine Carcinoma	Drug: PEN-221	Phase 1; Phase 2

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

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	90 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Actual Study Start Date :	December 8, 2016
Estimated Primary Completion Date :	June 2019
Estimated Study Completion Date :	December 2019

Arms and Interventions

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Arm	Intervention/treatment
Experimental: PEN-221; intravenous administration of PEN-221	Drug: PEN-221; Administration of PEN-221 once every three weeks

Outcome Measures

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Primary Outcome Measures :

1. High Grade (>=Grade 3) 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.
2. Phase 2a: Efficacy of PEN-221 as determined by RECIST 1.1 [ Time Frame: Baseline, every 6 weeks (SCLC) or every 9 weeks (NET) up to time of disease progression or death (estimated 36 months) ]
   Objective response rate (ORR) defined as the percentage of participants with best overall response of either complete response (CR) or partial response (PR) according to RECIST 1.1
3. Phase 2a: Duration of response (DOR) [ Time Frame: estimated 36 months ]
   Duration of response (DOR) defined as the time between the date of first response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause, whichever comes first

Secondary Outcome Measures :

1. Maximum concentration of PEN-221 and its metabolites (Cmax) [ Time Frame: up to 2 months ]
   Maximum concentration of PEN-221 concentration in circulating blood
2. Area under the curve (AUC) of PEN-221 and its metabolites [ Time Frame: up to 2 months ]
   Area under PEN-221 concentration v time curve in circulating blood
3. Half-life (t1/2) of PEN-221 and its metabolites [ Time Frame: up to 2 months ]
   Half life of PEN-221 concentration in circulating blood
4. 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 ]
   Radiographic progression free survival based on assessment of tumor size by CT or MRI (RECIST 1.1)
5. 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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• M/F at least 18 years old
• 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 administration 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, 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 specificied in one of the criteria listed below:

• Well differentiated, low, intermediate, or high-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 or peptide receptor radionuclide therapy (PRRT).
• Well differentiated, low, intermediate, or high-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 liverdirected 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)
• Platinum-sensitive SCLC after having received up to two prior lines of anticancer therapy, including at least one prior line of a platinum (monotherapy or platinum containing chemotherapy regimen). Patients are eligible only if they had a response (partial or complete) to their most recent platinum and their disease progressed greater than 60 days after completing their most recent platinum. Patients may have received another non-platinum containing regimen, such as topetecan, immunotherapy, or an investigational agent, as their most recent line of therapy, so long as they are deemed platinum sensitive per the above definition.

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 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 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 and not requiring steroids for at least 4 weeks prior to start of study treatment (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)
• Major surgery within 28 days of first drug dose
• Female pregnant or breast feeding
• Evidence of severe uncontrolled systemic disease, bleeding diatheses, renal or liver transplant, active infection with hep B or C or HIV
• Hypersensitivity or anaphylactic reaction to any somatostatin analog or to maytansinoids

Contacts and Locations

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Contacts

Contact: Tarveda Clinical Information Center		clinical.information@tarveda.com

Locations

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

Sponsors and Collaborators

Tarveda Therapeutics

More Information

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Responsible Party:	Tarveda Therapeutics
ClinicalTrials.gov Identifier:	NCT02936323 History of Changes
Other Study ID Numbers:	PEN-221-001
First Posted:	October 18, 2016
Last Update Posted:	April 26, 2018
Last Verified:	April 2018

Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

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; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site	Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adenocarcinoma; Somatostatin; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs