Clinical trial NCT05616624: ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers
Official title: ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non Small Cell Lung Cancer
Non-small Cell Lung Cancer
Small-cell Lung Cancer
Small Cell Lung Carcinoma
Keywords: Arginine Starvation
ADI-PEG20
SCLC
NSCLCa
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: Polaris Group
First posted: 2022-11-15
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: In this study, patients with small cell or non-small cell lung cancer will receive ADI-PEG 20, gemcitabine, and docetaxel after demonstrated progression on frontline therapy. In phase I of the study, up to 6 dose levels will be tested to find the recommended phase II dose (RP2D), after which patients enrolling to phase II will be treated at that dose level to assess efficacy. Although safety and tolerability has been previously determined in the sarcoma population, dose de-escalations of the chemotherapies in that patient population were required. Therefore, a phase I portion will be incorporated to determine the RP2D of the triplet in this population.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed extensive stage small cell or metastatic non-small cell lung cancer that has progressed on frontline therapy who are fit for treatment with gemcitabine and docetaxel in the opinion of the treating physician. Phase II enrollment will occur separately to the SCLC and NSCLC cohorts, with up to 36 enrolled in each cohort.
* Measurable disease per RECIST 1.1.
* Treated with at least one previous line of systemic therapy. The allowable window between treatments is 21 days for chemotherapy or a TKI or 5 half-lives for a TKI (whichever is shorter), 21 days and progression by CT for immunotherapy, 21 days for RT, 21 days for surgery, or 28 days for an investigational agent.

  * Patients with ES-SCLC must have been treated with first-line therapy of platinum doublet + anti-PD(L)1 therapy, if eligible.
  * Patients with NSCLC without a driver mutation must have been treated with first-line therapy of platinum doublet + anti-PD(L)1 therapy, if eligible.
  * Patients with NSCLC with a driver mutation (EGFR, ALK, ROS1) must have been treated with an FDA approved targeted therapy and subsequent platinum doublet therapy, if eligible.
* At least 18 years of age.
* ECOG performance status ≤ 1.
* Normal bone marrow and organ function as defined below:

  * Absolute neutrophil count ≥ 1.5 K/cumm
  * Platelets ≥ 100 K/cumm
  * Hemoglobin ≥ 9 g/dL
  * Total bilirubin ≤ 2 x IULN, patients with Gilberts must be below 3xIULN
  * AST(SGOT)/ALT(SGPT) ≤ 3 x IULN (or ≤ 5 x IULN if liver metastases are present)
  * Creatinine clearance \> 60 mL/min by MDRD or by 24 hour urine
  * Serum uric acid ≤ 8 mg/dL (with or without medication control)
* The effects of ADI-PEG 20 on the developing human fetus are unknown. For this reason and because chemotherapeutics are known to be teratogenic, women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry, for the duration of study participation, and for one month after completion of study treatment. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for one month after completion of study treatment.
* Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

* A history of other malignancy with the exception of:

  * Malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease
  * Basal cell or squamous cell carcinoma of the skin which was treated with local resection only
  * Carcinoma in situ of the cervix
  * Other tumors discussed with the study PI
* Currently receiving any other investigational agents.
* Prior treatment with ADI-PEG 20 or gemcitabine (prior docetaxel is allowed).
* Presence of untreated or unstable brain metastases. Patients with treated/stable brain metastases, defined as patients who have received prior therapy for their brain metastases and whose CNS disease is radiographically stable at study entry, are eligible.
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, gemcitabine, pegylated compounds, or other agents used in the study.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
* History of seizure disorder not related to underlying cancer.
* Grade 2 or higher neuropathy
* Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
* Patients with known active Hepatitis B or C or HIV.

Primary outcomes:
measure: Recommended phase II dose (Phase I only)
timeFrame: Through the first 4 weeks of treatment for all Phase I enrolled participants (estimated to be 12 months and 4 weeks)
measure: Treatment-related serious adverse event (SAE) rate (Phase I only)
timeFrame: From start of treatment through 30 days after completion of treatment (estimated to be 106 weeks)
measure: Objective response rate (ORR) (Phase II only - compared between non-small cell lung and small cell lung)
timeFrame: Through completion of treatment (estimated to be 102 weeks)
Secondary outcomes:
measure: Progression-free survival (PFS) (Phase II only - compared between non-small cell lung and small cell lung)
timeFrame: Through completion of follow-up (estimated to be up to 362 weeks)
measure: Overall survival (OS) (Phase II only - compared between non-small cell lung and small cell lung)
timeFrame: Through completion of follow-up (estimated to be up to 362 weeks)
measure: Clinical benefit rate (CBR) (Phase II only - compared between non-small cell lung and small cell lung)
timeFrame: Through completion of treatment (estimated to be 102 weeks)
measure: Cancer-related mortality rate (Phase II only - compared between non-small cell lung and small cell lung)
timeFrame: Through completion of follow-up (estimated to be up to 362 weeks)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
Study officials:
affiliation: Washington University School of Medicine
name: Brian A Van Tine, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: