High-Dose Ascorbic Acid in Treating Patients with Stage IIIB-IV Non-small Cell Lung Cancer

Status: Active

Description

This phase II trial studies how well high-dose ascorbic acid works in treating patients with stage IIIB-IV non-small cell lung cancer. Ascorbic acid given at high-dose may cause tumor cells to die and may also increase the effectiveness when it's given together with chemotherapy.

Eligibility Criteria

Inclusion Criteria

  • Patients must have newly diagnosed histologically or cytologically confirmed NSCLC, staged IIIB or IV, for which they have not received first-line cytotoxic chemotherapy (first-line epidermal growth factor receptor [EGFR] inhibitors or anaplastic lymphoma kinase [ALK] inhibitors are allowed given disease progression)
  • Patient with recurrent disease for whom palliative intent systemic therapy is indicated are also eligible regardless of stage of their disease; patients who received prior neo-adjuvant, adjuvant chemotherapy or chemo-radiation or radiation with curative intent for non-metastatic NSCLC must have experienced a treatment-free interval of at least 6 months from signing the informed consent since the last chemotherapy or chemo-radiation or radiation treatment/cycle; patients developing recurrent disease while receiving consolidation immunotherapy after definitive chemo-radiation or surgery for whom palliative intent therapy is indicated will be eligible for the study as far as their last cycle of immunotherapy is 3 weeks from the day of consent (6 months’ time-line is not applicable to consolidation immunotherapy)
  • Patients with central nervous system (CNS) metastasis will be allowed on the study if the metastasis is treated, no clinical signs of metastasis progression following treatment, and the patient is off steroids for at least 3 days (only if steroids are prescribed specifically for brain metastasis)
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count (ANC) >= 1500 cells per mm^3 (obtained within 21 days of cycle 1, day 1)
  • Platelets >= 100,000 per mm^3 (obtained within 21 days of cycle 1, day 1)
  • Hemoglobin >= 8 g/dL (obtained within 21 days of cycle 1, day 1)
  • Creatinine =< 1.5 mg/dL x the institutional upper limit of normal (obtained within 21 days of cycle 1, day 1)
  • Total bilirubin =< 1.5 mg/dL x the institutional upper limit of normal (obtained within 21 days of cycle 1, day 1)
  • Alanine aminotransferase (ALT) =< 3 times the institutional upper limit of normal (obtained within 21 days of cycle 1, day 1)
  • Aspartate aminotransferase (AST) =< 3 times the institutional upper limit of normal (obtained within 21 days of cycle 1, day 1)
  • Tolerate a 15 g ascorbate infusion (screening dose)
  • Not pregnant; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while receiving study drug, she should inform her treating physician immediately; pregnancy tests will be obtained per physician discretion
  • Not breastfeeding
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

  • Known sensitizing EGFR mutations or ALK gene rearrangement; if patient’s biopsy did not allow EGFR or ALK gene analysis (e.g., inconclusive, not enough tissue, etc.), the patient is considered eligible for study; enrollment on this clinical trial after progression on targeted therapy is allowed
  • Patient with strong PD-L1 expression (>= 50% of tumor cells expressing PD-L1 or tumor proportion score [TPS] >= 50%) will be excluded; patient’s with unknown PD-L1 expression or when PD-L1 expression can’t be determine; at progression or due to intolerable toxicity on immunotherapy, these patients will then be eligible for the study
  • Receiving warfarin therapy and cannot tolerate drug substitution
  • Active hemoptysis within 1 week of screening (more than 1/2 teaspoon per day)
  • Actively receiving insulin at time of ascorbate infusion (unless an exception is granted by the Investigational New Drug [IND] sponsor, medical monitor, and the principal investigator [PI])
  • Leptomeningeal disease
  • G6PD (glucose-6-phosphate dehydrogenase) deficiency
  • Patients who are on the following drugs and cannot have a drug substitution: flecainide, methadone, amphetamines, quinidine, and chlorpropamide
  • Patient with known active invasive malignancy other than NSCLC (exceptions: non-melanoma skin cancer or carcinoma in-situ of the cervix or bladder)
  • Patients may not be receiving any other investigational agents with the intention to treat their cancer (imaging trials are acceptable)
  • Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Known human immunodeficiency virus (HIV)-positive individuals

Locations & Contacts

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Contact: Muhammad Furqan
Phone: 319-356-4200

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Determine initial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria.

SECONDARY OBJECTIVES:

I. Determine the median time to progression for patients with stage IIIB/IV non-small cell lung cancer (NSCLC) treated with high dose ascorbate (ascorbic acid) when administered concurrently with carboplatin and paclitaxel.

II. Determine the progression free survival and overall survival of patients with stage IIIB/IV NSCLC treated with high dose ascorbate when administered concurrently with carboplatin and paclitaxel.

III. Determine the incidence of toxicity with the 3 drug combination of paclitaxel, carboplatin and ascorbate.

OUTLINE:

Patients receive high-dose ascorbic acid intravenously (IV) over 30-120 minutes twice weekly and paclitaxel IV over 3 hours and carboplatin IV over 1-2 hours once every 21 days. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response, partial response, or stable disease may receive 2 additional courses of therapy.

After completion of study treatment, patients are followed up at 28 days and then every 3-4 months for 2 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Iowa / Holden Comprehensive Cancer Center

Principal Investigator
Muhammad Furqan

Trial IDs

Primary ID 201412760
Secondary IDs NCI-2015-00709
Clinicaltrials.gov ID NCT02420314