PEN-866 in Patients With Advanced Solid Malignancies

NCT03221400 | Unknown Phase 1 FDA Drug

• 1 other identifier: PEN-866-001
• Study Type: interventional
• Target: 340
• Locations: 1 country
• Sites: 16

Brief Summary

Protocol PEN-866-001 is an open-label, multi-center, first-in-human Phase 1/2a study evaluating PEN-866 in patients with advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies.

Conditions

Carcinoma; Endometrial Adenocarcinoma; Neoplasms; Squamous Cell Carcinoma of the Anus; Adenocarcinoma of the Pancreas; Advanced Cancer; Solid Tumor; Solid Carcinoma; Squamous Cell Carcinoma of the Cervix; Squamous Cell Carcinoma; Squamous Cell Carcinoma of the Vulva; Squamous Cell Carcinoma of the Penis; Gastric Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma; Small-cell Lung Cancer; Small Cell Lung Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (7)

• Phase 1a and 1b : Incidence of Dose-Limiting Toxicities (DLTs)

  The Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) will be determined by assessing the incidence of DLTs and treatment related adverse events of PEN-866 as a single agent (Phase 1a) or in combination therapy (Phase 1b).

  Patients will be followed for 28 days to determine the incidence of DLTs.

• All Phases: Incidence of treatment related adverse events (Safety and tolerability)

  Safety and tolerability will be determined by assessing the incidence of treatment related adverse events.

  From date of first treatment/trial entry up to 28 days following the last treatment.

• Phase 2a: Efficacy of PEN-866 in patients with SCLC using best overall response rate

  Efficacy of PEN-866 in patients with SCLC will be assessed using best overall tumor response rate defined as complete response (CR) or partial response (PR) according to RECIST 1.1.

  From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months

• Phase 2a: Efficacy of PEN-866 in patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma using best overall response rate

  Efficacy of PEN-866 in patients with gastric or GEJ adenocarcinoma will be assessed using best overall tumor response rate defined as CR or PR according to RECIST 1.1.

  From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months

• Phase 2a: Efficacy of PEN-866 in patients with pancreatic adenocarcinoma using Disease Control Rate (DCR)

  Efficacy of PEN-866 in patients with pancreatic adenocarcinoma will be assessed using DCR defined as a best response of CR, PR, or stable disease (SD) according to RECIST 1.1.

  From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months

• Phase 2a: Efficacy of PEN-866 in patients with endometrial adenocarcinoma using best overall response rate

  Efficacy of PEN-866 in patients with endometrial adenocarcinoma will be assessed using best over all tumor response rate defined as CR or PR according to RECIST 1.1.

  From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months

• Phase 2a: Efficacy of PEN-866 in patients with squamous cell carcinoma of the genitalia (anus, cervix, vulva, or penis) using best overall response rate

  Efficacy of PEN-866 in patients with squamous cell carcinoma of the genitalia will be assessed using best over all tumor response rate defined as CR or PR according to RECIST 1.1.

  From the date of first treatment through the date of first documented progression, assessed up to (estimated) 18 months

Secondary Outcomes (11)

• Maximum concentration (Cmax) of PEN-866 and its components (HSP90 ligand and SN-38)

  1 Month (Phase 1a); 14 days (Phase 1b); assessed up to (estimated) 18 months for Phase 2a

• Area under the curve (AUC) of PEN-866 and its components (HSP90 ligand and SN-38)

  1 Month (Phase 1a); 14 days (Phase 1b); assessed up to (estimated) 18 months for Phase 2a

• Half-life (t1/2) of PEN-866 and its components (HSP90 ligand and SN-38)

  1 Month (Phase 1a); 14 days (Phase 1b); assessed up to (estimated) 18 months for Phase 2a

• Phase 1b: Characterize the plasma pharmacokinetics (PK) of the combination therapies and their components

  14 days

• Phase 1a: Tumor response using RECIST 1.1 criteria

  Baseline and every 6 weeks until date of first documented progression or death (estimated 6 months)

Study Arms (4)

Phase 1a PEN-866 Sodium (Single Agent)

EXPERIMENTAL

Dose escalation of PEN-866 Sodium administered intravenously

Drug: PEN-866 Sodium

Phase 1b PEN-866 Sodium + Flurouracil + Folinic Acid

EXPERIMENTAL

Dose escalation of intravenous administration of PEN-866 Sodium in combination with fluorouracil and folinic acid

Drug: PEN-866 Sodium; Drug: fluorouracil; Drug: Folinic acid

Phase 2a PEN-866 Sodium (Single Agent)

EXPERIMENTAL

Intravenously administered PEN-866 Sodium at the Recommended Phase 2 Dose

Drug: PEN-866 Sodium

Phase 1b PEN-866 Sodium + Niraparib

EXPERIMENTAL

Dose escalation of intravenous administration of PEN-866 Sodium in combination with niraparib

Drug: PEN-866 Sodium; Drug: Niraparib

Interventions

PEN-866 Sodium DRUG

PEN-866 Sodium is a miniaturized conjugate that comprises an HSP90 targeting ligand linked to SN-38, the active metabolite of irinotecan. PEN-866 is available as a sterile lyophilized powder for solution for infusion.

Phase 1a PEN-866 Sodium (Single Agent); Phase 1b PEN-866 Sodium + Flurouracil + Folinic Acid; Phase 1b PEN-866 Sodium + Niraparib; Phase 2a PEN-866 Sodium (Single Agent)

fluorouracil DRUG

Fluorouracil 2400 mg/m2 IV

Also known as: 5-Fluorouracil, 5-FU

Phase 1b PEN-866 Sodium + Flurouracil + Folinic Acid

Folinic acid DRUG

Folinic acid 400 mg/m2 IV

Also known as: Leucovorin

Phase 1b PEN-866 Sodium + Flurouracil + Folinic Acid

Niraparib DRUG

Niraparib

Also known as: Zejula

Phase 1b PEN-866 Sodium + Niraparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• M/F at least 18 years old
• Performance status 0 or 1
• Adequate bone marrow, liver, and kidney function within 28 days prior to first dose
• Serum potassium, calcium, magnesium, phosphorus within normal limits
• Adequate birth control
• Central venous access line is required
• Patients in Phase 1a must also have confirmed advanced solid malignancy that has progressed after one or more prior lines of anticancer therapy and no other standard of care therapies that are deemed appropriate for treatment of their malignancy
• Patients in Phase 2a must have measurable disease per RECIST 1.1 and documented disease progression during or after their most recent line of anticancer therapy.
• Patients in Phase 2a must have disease history specific to their disease as listed below:
• Small Cell Lung Cancer (SCLC): Patients with locally recurrent or metastatic SCLC whose disease has progressed after having received one or more prior lines of chemotherapy.
• Gastric or gastroesophageal (GEJ) adenocarcinoma: Patients with locally recurrent or metastatic gastric or GEJ adenocarcinoma whose disease has progressed after having received one or more prior lines of chemotherapy.
• Squamous cell carcinoma (SCC) of the genitalia (anus, cervix, vulva, or penis): Patients with locally recurrent or metastatic SCC of the genitalia (anus, cervix, vulva, or penis) whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed after postoperative adjuvant chemotherapy or neoadjuvant chemotherapy prior to radiation or surgery.
• Pancreatic adenocarcinoma (PDAC): Patients with locally recurrent or metastatic PDAC whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.
• Endometrial adenocarcinoma (EC): Patients with locally recurrent or metastatic EC whose disease has progressed after having received one or more prior lines of chemotherapy, including those whose disease has progressed within 6 months of postoperative adjuvant chemotherapy.
• For Phase 1b patients receiving PEN-866 in combination with fluorouracil and folinic acid only:

You may not qualify if:

• Treatment with anticancer therapy or investigational drug or device within 2 wk (6 wk for nitrosureas or mitomycin C) before C1D1, and any drug-related toxicities must have recovered to grade 1 or less with the exception of alopecia and peripheral neuropathy.
• Phase 2a only: Prior treatment with topoisomerase I inhibitor(s).
• Cardiac disease such as unstable angina within 6 months of screening, myocardial infarction within 6 months of screening, NY Heart Association Class III - IV 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.
• For Phase 1b patients receiving the Niraparib combination only: hypertension as defined as diastolic \> 90 mmHg or systolic \> 140 mmHg
• Stroke or transient ischemic attack within 6 months of screening
• Prior history of posterior reversible excephalopathy scyndrome (PRES).
• Peripheral neuropathy greater than grade 2
• Patients requiring medications with drugs that are inhibitors of UGT1A1 or substrates of CYP1A2, P-gP, BCRP, OATP1B1, OATP1B3 or OCT1 transporters
• Leptomeningeal disease or spinal cord compression unless controlled and asymptomatic with surgery, radiation, and not requiring steroids within 4 weeks prior to C1D1.
• Brain metastases unless previously treated and asymptomatic. Stable low dose of steroids is permitted.
• Major surgery within 28 days of first drug dose
• If 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 ganetespib or other HSP90 inhibitors, irinotecan, SN-38 or its derivatives
• Any medical, psychological, or social condition that would interfere with the patient's participation in the study.

Sponsors & Collaborators

• Tarveda Therapeutics: lead

Study Sites (16)

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

RECRUITING

Sarah Cannon Reasearch Institute at HealthONE

Denver, Colorado, 80218, United States

RECRUITING

Florida Cancer Specialists - South

Fort Myers, Florida, 33901, United States

RECRUITING

Florida Cancer Specialists - North

St. Petersburg, Florida, 33705, United States

RECRUITING

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401, United States

RECRUITING

National Institutes of Health / National Cancer Institute

Bethesda, Maryland, 20892, United States

RECRUITING

Henry Ford

Detroit, Michigan, 48202, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

RECRUITING

Stephenson Cancer Center, University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Sidney Kimmel Cancer Center at Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Prisma Health - Upstate

Greenville, South Carolina, 29605, United States

RECRUITING

The West Clinic

Germantown, Tennessee, 38138, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma; Neoplasms; Anus Neoplasms; Carcinoma, Squamous Cell; Stomach Neoplasms; Small Cell Lung Carcinoma

Interventions

Fluorouracil; Leucovorin; niraparib

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases; Neoplasms, Squamous Cell; Stomach Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Anish Thomas, MD

  National Cancer Institute (NCI)

  STUDY CHAIR

Central Study Contacts

Tarveda Clinical Information Center

CONTACT

(617) 923-4100; clinical.information@tarvedatx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2017
• First Posted: July 18, 2017
• Study Start: August 29, 2017
• Primary Completion: January 1, 2023
• Study Completion: June 1, 2023
• Last Updated: February 17, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (16)