PEGPH20, Gemicitabine and Nab-Paclitaxel for Pancreatic Ductal Adenocarcinoma

NCT02487277 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 144515NCI-2015-01213
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

We will be conducting a Phase II study investigating PEGPH20 in combination with gemcitabine and nab-paclitaxel in patients with borderline resectable pancreatic ductal adenocarcinoma (PDAC) at the Helen Diller Family Comprehensive Cancer Center at University of California, San Francisco (UCSF). There are multiple definitions of borderline resectable PDAC including the MD Anderson definition and the criteria developed during the Consensus Conference sponsored by the American Hepato-Pancreato-Biliary Association, Society of Surgical Oncology, and Society for Surgery of the Alimentary Tract. Borderline resectable PDAC cases will be identified per the definition developed in the currently running inter-group pilot trial for borderline resectable pancreatic cancer (NCT01821612). Per this trial, borderline resectable PDAC is defined as "presence of any one or more of the following on CT:

• An interface between the primary tumor and the superior mesenteric vein or portal vein (SMV-PV) measuring ≥ 180° of the circumference of the vessel wall
• Short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction
• Short segment interface (of any degree) between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and reconstruction.
• An interface between the tumor, and Superior mesenteric artery (SMA) measuring \< 180º of the circumference of the vessel wall. This trial will be conducted in two parts. In Part I, pre-treatment endoscopic ultrasound (EUS)-guided core biopsies of the pancreatic tumor, CA 19-9 levels and functional MRIs including Dynamic contrast-enhanced (DCE)-MRI and Diffusion-weighted magnetic resonance imaging (DWI-MRI) will be obtained for the first fifteen patients enrolled. After a 1-week run-in period with PEGPH20 on days 1 and 4, patients will have repeat EUS-guided core biopsies, functional MRI, CA 19-9 level and baseline CT chest, abdomen and pelvis. Subsequently, patients will be started on treatment with PEGPH20, gemcitabine and nab-paclitaxel given weekly for 3 weeks, every 28 days. To evaluate the disease response to treatment, CA 19-9 levels will be checked monthly and restaging CT chest, abdomen and pelvis will be obtained every 8 weeks. If there is disease progression at any point in the study, patients will be taken off of study and alternative treatments will be offered. At the completion of 4 cycles of therapy, restaging CT scans will be obtained to determine resectability. If the patients are found to have resectable disease, an additional functional MRI will be obtained to evaluate the PDAC stroma. If the patients are able to have successful surgeries, tissue analyses will be performed on the resected pancreatic tumor. These patients will then proceed to get 2 cycles of adjuvant chemotherapy with gemcitabine and nab-paclitaxel. If the patients are deemed to be surgical candidates but are found to have unresectable disease in the operating room, an intraoperative core biopsy of the pancreatic tumor will be obtained for tissue analyses. At the time of initiation of therapy with PEGPH20, patients will be started on prophylactic dose of enoxaparin 1 mg/kg subcutaneous daily. This will be continued throughout the study participation. In Part II, an additional 21 patients will be enrolled, and will begin neoadjuvant therapy with PEGPH20, gemcitabine and nab-paclitaxel without the 1 week run-in of PEGPH20-only or the pre- and post-run-in EUS-guided biopsies.

Conditions

Adenocarcinoma

Keywords

Pancreatic

Outcome Measures

Primary Outcomes (2)

• Incidence of Clinically Relevant Pancreatic Fistula

  Our study will be investigating only clinically relevant pancreatic fistulas, i.e. grades B or C. Descriptive statistics will be used report the incidence of pancreatic fistula within the 7-day post-operative period after neoadjuvant treatment

  Up to 5 years

• Rate of Pathologic Complete Response (pCR)

  Descriptive statistics with frequency / proportion will be used to evaluate rate of pathologic complete response using the pathological exam of resected tumors. pCR was defined as area of scarring in pancreatic parenchyma and/or peripancreatic soft tissue with chronic inflammation, with or without acellular mucin pools and histiocytic infiltrates, but no residual viable invasive adenocarcinoma cells in the pancreatectomy specimen

  Up to 5 years

Secondary Outcomes (4)

• Percent Change of CA19-9 Response Rate

  Up to 5 years

• Margin-Negative (R0) Resection Rate

  Up to 5 years

• Overall Response Rate (ORR)

  Up to 5 years

• Disease Free Survival (DFS)

  Up to 5 years

Study Arms (2)

Combination therapy with 1 week Run-In

EXPERIMENTAL

PEGPH20: 3ug/kg on Days 1 and 4 1 cycle = 28 days PEGPH20: 3ug/kg on Days 1, 8, 15 Gemcitabine: 1000mg/m\^2 on Days 1, 8, 15 Nab-paclitaxel: 125mg/m\^2 on Days 1, 8, 15

Drug: PEGPH20; Drug: Gemcitabine; Drug: Nab-paclitaxel

Combination therapy alone

EXPERIMENTAL

1 cycle = 28 days PEGPH20: 3ug/kg on Days 1, 8, 15 Gemcitabine: 1000mg/m\^2 on Days 1, 8, 15 Nab-paclitaxel: 125mg/m\^2 on Days 1, 8, 15

Drug: PEGPH20; Drug: Gemcitabine; Drug: Nab-paclitaxel

Interventions

PEGPH20 DRUG

Combination therapy alone; Combination therapy with 1 week Run-In

Gemcitabine DRUG

Combination therapy alone; Combination therapy with 1 week Run-In

Nab-paclitaxel DRUG

Combination therapy alone; Combination therapy with 1 week Run-In

Eligibility Criteria

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

You may qualify if:

• Greater than or equal to 18 years old
• Histologically confirmed pancreatic adenocarcinoma
• Borderline resectable disease
• Performance status of Eastern Cooperative Oncology Group (ECOG) of 0-1
• Therapy naïve
• Evaluable disease with either:
• RECIST-defined measurable disease
• An elevated serum CA19-9 \>100 u/ml
• Adequate organ function including:
• Bone marrow: Absolute Neutrophil Count (ANC) ≥1500/mm3, platelets ≥100,000/mm3 and hemoglobin ≥ 9 g/dL
• Hepatic: Serum total bilirubin ≤1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) and aspartate aminotransferase (AST)/ serum glutamic-oxaloacetic transaminase (SGOT) ≤ 2.5 x ULN.
• Renal: Serum creatinine (sCr) ≤ 1.5 x ULN, or creatinine clearance (Ccr) ≥ 40 mL/min as calculated by the Modified Cockcroft-Gault formula.
• Peripheral neuropathy \< grade 2
• Alkaline phosphatase ≤ 2 times the ULN unless bone metastasis is present in the absence of liver metastasis

You may not qualify if:

• Age younger than 18 years old
• Locally advanced or metastatic disease
• Known allergy to hyaluronidase
• Contraindications to prophylactic dose low molecular weight heparin (LMWH) , including
• Patients with recent gastrointestinal bleeding
• History of heparin induce thrombocytopenia on LMWH
• Subjects with previous severe hemorrhagic events on LMWH
• Known contraindications to heparin including:
• Recent central nervous system bleed, intracranial or spinal lesion at high risk for bleeding
• Active bleeding (major): more than 2 units transfused in 24 hours
• Spinal anesthesia/lumbar puncture within the past month
• Chronic, clinically significant measurable bleeding \> 48 hours
• Severe platelet dysfunction (uremia, medications, dysplastic hematopoiesis)
• Recent major operation at high risk for bleeding
• Underlying hemorrhagic coagulopathy High risk for falls (head trauma)

Sponsors & Collaborators

• Andrew Ko: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Adenocarcinoma

Interventions

PEGPH20; Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Study was terminated earlier than expected due to low accrual so no participants were enrolled in the "Combination therapy alone" treatment arm.

Results Point of Contact

• Title: Dr. Andrew Ko
• Organization: University of California, San Francisco

Andrew.Ko@ucsf.edu

(415) 353-7286

Study Officials

• Andrew Ko, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Clinical Medicine

Study Record Dates

• First Submitted: June 29, 2015
• First Posted: July 1, 2015
• Study Start: July 14, 2015
• Primary Completion: May 18, 2018
• Study Completion: May 18, 2018
• Last Updated: January 2, 2020
• Results First Posted: January 2, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)