Study of Paclitaxel Protein Bound + Gemcitabine + Cisplatin + Hydroxychloroquine as Treatment in Untreated Pancreas Cancer

• Paclitaxel protein bound (Drug): combination therapy
• Gemcitabine (Drug): combination therapy
• Cisplatin (Drug): combination therapy
• Hydroxychloroquine (Drug): combination therapy

Primary outcomes

• CA 19-9 Normalization [From enrollment to the end of study, up to 30 weeks.]: Laboratory measurements of CA 19-9, a circulating tumor biomarker, were collected on Day 1 of every treatment cycle (approximately 21 days/cycle); CA 19-9 normalization after 2 or more treatment cycles was measured.

Secondary outcomes

• Resectability Rate (R0) [After end of treatment, from 6 months up to 2 years.]: The percentage of participants whose tumors could be completely removed by surgery after receiving study regimen with no cancer cells left at margins (R0).
• Pathologic Complete Response Rate (pCR) [After end of treatment, from 6 months up to 2 years.]: Pathological complete response rate (pCR) is defined here as the absence of detectable cancer after surgical resection. Participants received a CT/MRI scan after surgical resection to monitor response using RECIST 1.1 criteria.
• Radiological Response - Complete Response (CR) or Partial Response (PR) [From enrollment to end of study, up to 30 weeks.]: Objective measurement of changes in tumor size upon imaging after treatment per RECIST v1.1 criteria; percentage of participants reporting Complete Response (CR; all tumors disappear) and Partial Response (PR; >30% decrease in tumor size).
• Radiological Response - All Responses [From enrollment to the end of study, up to 30 weeks.]: Objective measurement of changes in tumor size upon imaging after treatment per RECIST v1.1 criteria. Complete Response (CR; all tumors disappeared), Partial Response (PR; >30% decrease in tumor size), Stable Disease (SD; no change), and Progressive Disease (PD; >20% increase in tumor size or new lesions).
• 2-Year Survival [2 years after study completion]: Participants were contacted by telephone every 12 weeks to monitor survival until date of death. Participants surviving up to 2 years are reported.
• Overall Survival [Every 12 weeks from study entry, up to 32 months.]: Participants were contacted by telephone every 12 weeks to monitor survival until date of death.
• Adverse Events Related to Study Agents [From enrollment to end of study, up to 30 weeks.]: The number of patients who experienced an adverse event (AE) determined to be related to one or more of the study agents. Adverse events occurring were graded according to the NCI Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Grade refers to the severity of the AE and are given on a 1-5 scale, with each scale having unique clinical descriptions of severity for each AE based on this general guideline: Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate; minimal, local or noninvasive intervention indicated. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

Other outcomes

• Quality of Life - Brief Pain Inventory (BPI), Pain Severity Score [From enrollment to end of study, up to 30 weeks.]: The Brief Pain Inventory (BPI) is a standard questionnaire administered to participants to measure cancer pain intensity and the impact of pain on daily life in the past 24 hours. Pain severity was assessed with a scale range of 0-10, 0=no pain, 10=worst imaginable. Multiple question results were combined into a single pain severity score per patient on the 0-10 scale range. Data is presented as the median of baseline scores ("Baseline") (n=11), median of end of treatment (EOT) scores ("End of Treatment (EOT)") (n=11), and median of within-subject change scores calculated as EOT minus baseline scores ("Change Between Baseline and EOT") (n=11).
• Quality of Life - Brief Pain Inventory (BPI), Pain Interference Score [From enrollment to end of study, up to 30 weeks.]: The Brief Pain Inventory (BPI) is a standard questionnaire administered to participants to measure cancer pain intensity and the impact of pain on daily life in the past 24 hours. Pain interference was assessed with a scale range of 0-10, 0=does not interfere, 10=completely interferes. Multiple question results were combined into a single pain interference score per patient on the 0-10 scale range. Data is presented as the median of baseline scores ("Baseline") (n=11), median of end of treatment (EOT) scores ("End of Treatment (EOT)") (n=11), and median of within-subject change scores calculated as EOT minus baseline scores ("Change Between Baseline and EOT") (n=11).
• Quality of Life - MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI), Core Symptom Severity Score [From enrollment to end of study, up to 30 weeks.]: The MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI) is a questionnaire designed to assess the severity and impact of cancer symptoms on daily life activities. Core symptom severity within the last 24 hours was assessed with a scale range of 0-10, 0=not present, 10=worst imaginable. The reported severity of multiple symptoms was combined into a single overall symptom severity score for each patient on the 0-10 scale range. Data is presented as the median of baseline scores ("Baseline") (n=11), median of end of treatment (EOT) scores ("End of Treatment (EOT)") (n=11), and median of within-subject change scores calculated as EOT minus baseline scores ("Change Between Baseline and EOT") (n=11).
• Quality of Life - MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI), GI Module Score [From enrollment to end of study, up to 30 weeks.]: The MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI) is a questionnaire designed to assess the severity and impact of cancer symptoms on daily life activities. The GI module asks specific questions related to GI symptoms and asks users to rank the severity of symptoms using a 0-10 scale, 0=not present, 10=worst imaginable. The reported severity of multiple GI symptoms was combined into a single GI module score for each patient on the 0-10 scale range. Data is presented as the median of baseline scores ("Baseline") (n=11), median of end of treatment (EOT) scores ("End of Treatment (EOT)") (n=11), and median of within-subject change scores calculated as EOT minus baseline scores ("Change Between Baseline and EOT") (n=11).
• Quality of Life - MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI), Overall Symptom Interference With Daily Life Score [From enrollment to end of study, up to 30 weeks.]: The MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI) is a questionnaire designed to assess the severity and impact of cancer symptoms on daily life activities. Symptom interference with daily life activities within the last 24 hours was measured using a 0-10 scale, 0=does not interfere, 10=interferes completely. The reported interference for multiple daily activities was combined into a single symptom interference score for each patient on the 0-10 scale range. Data is presented as the median of baseline scores ("Baseline") (n=11), median of end of treatment (EOT) scores ("End of Treatment (EOT)") (n=11), and median of within-subject change scores calculated as EOT minus baseline scores ("Change Between Baseline and EOT") (n=11).

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Patient has histologically or cytologically confirmed resectable, borderline resectable, or locally advanced (unresectable) PDAC (based upon Tempero et al 2016)
* Age ≥ 18 years.
* If a female patient is of child-bearing potential, she must have a negative serum pregnancy test (≥β-hCG) documented within 72 hours of the first administration of study drug
* If sexually active, the patient and partner must agree to use contraception considered adequate and appropriate by the Investigator
* Patient must have received no prior chemotherapy or radiation therapy for PDAC
* Patients must have normal organ and marrow function
* Patient has acceptable coagulation status as indicated by an INR ≤ 1.5 x ULN. Patients on anticoagulation can be included at the discretion of the investigator.
* Karnofsky Performance Status (KPS) of ≥70%.
* Have an elevated CA 19-9 (>2X ULN) in the context of normal bilirubin

Exclusion Criteria:

* Patient will be excluded from this study if any of the following criteria apply: Evidence of metastatic disease. No metastatic disease defined as any one or more of the following; Suspicious lymphadenopathy outside of the standard surgical field (i.e. aortocaval nodes, distant abdominal nodes) or Radiographic evidence for metastatic disease in distant organs, peritoneum, or ascites
* Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy.
* Known infection with HIV, hepatitis B, or hepatitis C.
* Has undergone major surgery, other than diagnostic surgery (i.e.--surgery done to obtain a biopsy for diagnosis without removal of an organ), within 4 weeks prior to Day 1 of treatment in this study.
* History of allergy or hypersensitivity to the study drugs.
* Serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the patient to receive an experimental research drug.
* Current, serious, clinically significant cardiac arrhythmias as determined by the investigator.
* Patient is unwilling or unable to comply with study procedures.
* Patient is enrolled in an industry sponsored clinical trial involving treatment with investigational therapy. Patients enrolled in HonorHealth sponsored research studies may be eligible to participate as long as their participation in the other research studies does not confound the data collected for this study.
* Patient with a history of interstitial lung disease, history of slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.
* Use of non-FDA approved cannabinoids are prohibited. Total daily usage of up to 40 mg per day of marinol is acceptable.

Exclusion Criteria for Hydroxychloroquine Expansion Cohort only:

* Prolonged QTcF > 450 ms for men and > 470 ms for women at Screening. Electrolyte imbalances (e.g. hypokalemia/hypomagnesemia/hypocalcemia) must be corrected prior to first dose of hydroxychloroquine.
* Known second or third degree atrioventricular block.
* Patient is taking a concomitant medication that has "known" risk of QT prolongation or torsdades de pointe.
* Patient has pre-existing retinopathy.
* Patient has known hypersensitivity to hydroxychloroquine or other 4-aminoquinoline compounds.

Participant flow

Outcome results

• CA 19-9 Normalization (Primary), Number, Percentage of participants: Treatment 9.1 (0.2 to 41.3)
• Resectability Rate (R0) (Secondary), Number, Percentage of participants: Treatment 100 (39.8 to 100.0)
• Pathologic Complete Response Rate (pCR) (Secondary), Number, Percentage of participants: Treatment 0.0 (0.0 to 60.2)
• Radiological Response - Complete Response (CR) or Partial Response (PR) (Secondary), Number, Percentage of participants: Treatment 50.0 (18.7 to 81.3)
• Radiological Response - All Responses (Secondary), Count of participants, Participants: Treatment 1
• 2-Year Survival (Secondary), Number, Percentage of participants: Treatment 36.4 (10.9 to 69.2)
• Overall Survival (Secondary), Median, Months: Treatment 18.5 (11.4 to 31.7)
• Adverse Events Related to Study Agents (Secondary), Count of participants, Participants: Treatment 1
• Quality of Life - Brief Pain Inventory (BPI), Pain Severity Score (Other pre specified), Median, BPI Pain Severity Score: Treatment 1.8 (0.0 to 3.2) (p 0.457)
• Quality of Life - Brief Pain Inventory (BPI), Pain Interference Score (Other pre specified), Median, BPI Pain Interference Score: Treatment 2.1 (0.0 to 3.9) (p 0.227)
• Quality of Life - MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI), Core Symptom Severity Score (Other pre specified), Median, MDASI-GI Core Symptom Severity Score: Treatment 2.5 (0.6 to 3.7) (p 0.331)
• Quality of Life - MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI), GI Module Score (Other pre specified), Median, MDASI-GI GI Module Score: Treatment 2.0 (0.0 to 3.2) (p 0.064)
• Quality of Life - MD Anderson Symptom Inventory for Gastrointestinal Cancer (MDASI-GI), Overall Symptom Interference With Daily Life Score (Other pre specified), Median, MDASI-GI Symptom Interference Score: Treatment 2.3 (0.0 to 5.2) (p 0.231)

Adverse events

Time frame: Adverse events were assessed from enrollment through 30 days post-study, up to 30 weeks. Deaths were assessed from enrollment until end of follow-up, up to 32 months.

Serious adverse events by term

Other adverse events by term

34 more terms not shown.

• Study Protocol and Statistical Analysis Plan (PDF, 2022-03-03)

• Erkut Borazanci, MD, Principal investigator, HonorHealth Research Institute