QUILT-2.022 NANT-008 in Combination w/ 5-fluorouracil, Bevacizumab, Leucovorin & Oxaliplatin in Subjects With Pancreatic Cancer

NCT03127124 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: QUILT-2.022
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1b/2 study to evaluate the safety and efficacy of NANT-008 in combination with 5-fluorouracil, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.

Conditions

Pancreatic Adenocarcinoma Metastatic

Outcome Measures

Primary Outcomes (2)

• Phase 1b Primary Endpoint

  Determine the recommended phase 2 dose (RP2D) of NANT-008 and dose-limiting toxicities (DLTs) of NANT-008

  12 weeks

• Phase 2 Primary Endpoint

  Evaluate the efficacy of the tested regimen as assessed by the 1 year survival rate

  1 year

Study Arms (1)

NANT-008 in combination with other agents

EXPERIMENTAL

NANT-008 will be administered in combination with 5-fluorouracil, bevacizumab, leucovorin, and oxaliplatin in patients with metastatic pancreatic adenocarcinoma.

Drug: NANT-008; Drug: Fluorouracil Injectable Product; Drug: Avastin Injectable Product; Drug: Leucovorin Calcium Injection; Drug: Eloxatin Injectable Product

Interventions

NANT-008 DRUG

Paclitaxel: benzenepropanoic acid, β-(benzoylamino)-α-hydroxy-(2aR, 4S, 4aS, 6R, 9S, 11S, 12S, 12aR, 12bS)-6,12b-bis(acetyloxy)-12-(benzoyloxy)-2a, 3, 4, 4a, 5, 6, 9, 10, 11, 12, 12a, 12b-dodecahydro-4,11-dihydroxy-4a, 8, 13, 13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca\[3,4\]benz\[1,2-b\]oxet-9-y1ester,(αR,βS)-(9CI)

NANT-008 in combination with other agents

Fluorouracil Injectable Product DRUG

5-fluoro-2,4 (1H,3H)-pyrimidinedione.

NANT-008 in combination with other agents

Avastin Injectable Product DRUG

Recombinant humanized monoclonal IgG1 antibody

NANT-008 in combination with other agents

Leucovorin Calcium Injection DRUG

Calcium N -\[p -\[\[\[(6RS )-2-amino-5-formyl-5,6,7,8-tetrahydro-4-hydroxy-6-pteridinyl\]methyl\]amino\]benzoyl\]-L-glutamate (1:1).

NANT-008 in combination with other agents

Eloxatin Injectable Product DRUG

cis-\[(1 R,2 R)-1,2-cyclohexanediamine-N,N'\] \[oxalato(2-)- O,O'\] platinum.

NANT-008 in combination with other agents

Eligibility Criteria

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

You may qualify if:

• Male or female subject is between ≥ 18 and ≤ 65 years of age at the time of signing the informed consent form (ICF).
• Able to understand and provide a signed informed consent that fulfills the relevant IRB or IEC guidelines.
• Histologically confirmed, unresectable, locally advanced or metastatic pancreatic adenocarcinoma.
• ECOG performance status of 0 to 1.
• Have at least 1 measurable lesion and/or non-measurable disease evaluable according to RECIST Version 1.1.
• Have not received any prior treatment other than radiation therapy for symptomatic pain relief.
• Resolution of all toxic side effects of prior chemotherapy, radiotherapy, or surgical procedures to CTCAE grade ≤ 1, with the exception of alopecia.
• Must be willing to provide pre- and post-treatment blood samples for exploratory analyses.
• Ability to attend required study visits and return for adequate follow-up, as required by this protocol.
• Must have a recent FFPE tumor biopsy specimen following the conclusion of the most recent anticancer treatment and be willing to release the specimen for tumor molecular profiling analysis. If an historic specimen is not available, the subject must be willing to undergo a biopsy during the screening period.
• Agreement to practice effective contraception (both male and female subjects, if the risk of conception exists).
• Must have a stable, functioning stent at least 2 weeks before the beginning of the study (metal stents are preferred as per NCCN guidelines) if subject has had a previous biliary or pancreatic duct obstruction requiring stent placement.

You may not qualify if:

• History of previous systemic chemotherapy or investigational therapy.
• History of other active malignancies or brain metastasis except: controlled basal cell carcinoma or squamous cell carcinoma; prior history of in situ cancer (eg, breast, melanoma, squamous cell carcinoma of the skin, cervical) and \> 5 years without evidence of disease; prior history of prostate cancer that is not under active systemic treatment (except hormonal therapy) and with undetectable PSA (\< 0.2 ng/mL).
• Inadequate organ function, evidenced by the following laboratory results:
• White blood cell (WBC) count \< 3,500 cells/mm3
• Absolute neutrophil count \< 1,500 cells/mm3.
• Platelet count \< 100,000 cells/mm3.
• Hemoglobin \< 9 g/dL.
• Total bilirubin greater than the upper limit of normal (ULN) at time of enrollment; unless the subject has known history of Gilbert's syndrome.
• Aspartate aminotransferase (AST \[SGOT\]) or alanine aminotransferase (ALT \[SGPT\]) \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases).
• Alkaline phosphatase levels \> 2.5 × ULN (\> 5 × ULN in subjects with liver metastases, or \>10 × ULN in subjects with bone metastases).
• Serum creatinine \> 2.0 mg/dL or 177 μmol/L.
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) \>1.5 × ULN.
• Pre-existing peripheral neuropathy \> grade 1 based on NCI CTCAE V4.03.
• Current chronic daily treatment (continuous for \> 3 months) with systemic corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone), excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
• Positive results of screening test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV).

Sponsors & Collaborators

• NantPharma, LLC: lead

Study Sites (1)

Chan Soon-Shiong Institutes for Medicine

El Segundo, California, 90245, United States

Location

MeSH Terms

Interventions

Leucovorin

Intervention Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: April 25, 2017
• Study Start: February 27, 2018
• Primary Completion: December 6, 2023
• Study Completion: December 6, 2023
• Last Updated: April 2, 2024

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)