Trial Outcomes & Findings for Phase I/II Calcitriol in Lung Cancer (NCT NCT00794547)

NCT ID: NCT00794547

Last Updated: 2017-12-12

Results Overview

The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.

• Recruitment status: TERMINATED
• Study phase: PHASE1/PHASE2
• Target enrollment: 34 participants
• Primary outcome timeframe: 5 years
• Results posted on: 2017-12-12

Participant Flow

Participant milestones

Measure	Phase 1 In the Phase I part of the study, we will test the safety of calcitriol along with standard chemotherapy. In addition, the goal is to see what effects (good and bad) it has on you and your type of Non-Small Cell Lung Cancer. This study is ongoing. In this portion of the study, we are testing increasing doses of calcitriol in combination with standard chemotherapy. If 2/3 patients at any dose level experience side effects that are limiting, we will call the dose level below that dose the maximum tolerated dose. Calcitriol: Escalating dose of Calcitriol will be infused IV over 1 hour every 21 days.	Phase 2 In the Phase II part of the study, we will find out the response of subjects' cancer has to the combination of a fixed dose of calcitriol (determined in the phase I study) with standard chemotherapy. Calcitriol: In this portion of the study, all patients will get the same dose of calcitriol (determined from the Phase I study) along with the standard chemotherapy
Overall Study STARTED	18	16
Overall Study COMPLETED	18	16
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase I/II Calcitriol in Lung Cancer

Baseline characteristics by cohort

Measure	Calcitriol + Cisplatin + Docetaxel n=34 Participants Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	22 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants
Region of Enrollment United States	34 participants n=5 Participants
Histology Adenocarcinoma	21 participants n=5 Participants
Histology Squamous carcinoma	12 participants n=5 Participants
Histology NSCLC NOS	1 participants n=5 Participants
Performance Status Performance Status 0	16 participants n=5 Participants
Performance Status Performance Status 1	18 participants n=5 Participants
Smoking Status Never Smoker	2 participants n=5 Participants
Smoking Status Ever Smoker	29 participants n=5 Participants
Smoking Status Unknown	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years

Population: Eighteen patients were enrolled, and 16 were evaluable for toxicity assessments. Two patients were not evaluable as they progressed prior to completion of cycle 1.

The primary objective was to determine the Maximum Tolerated Dose (MTD) of intravenous calcitriol when administered prior to fixed dose cisplatin 75mg/m2 and docetaxel 75 mg/m2, every 3 weeks in patients with advanced non-small cell lung cancer (NSCLC). Accrual duration for the study is 5 years.

Outcome measures

Measure	Calcitriol + Cisplatin + Docetaxel n=16 Participants Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
MTD of Intravenous Calcitriol When Administered Prior to Fixed Dose Cisplatin 75mg/m2 and Docetaxel 75 mg/m2, Every 3 Weeks in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)	60 mcg/m^2

PRIMARY outcome

Timeframe: 30 days after last dose

Population: Thirty-four patients were enrolled (18 in phase I and 16 in phase II). 16 of 18 patients enrolled in the Phase 1 portion of the study were evaluable for toxicity. One patient in the phase II study went to another therapy prior to the 30 day window for a confirmatory scan and was thus excluded from analysis.

The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. Toxicity was assessed, in part, by noting the number of participants that experience grade 3 or greater neutropenia in each phase of the trial. Toxicities were recorded using NCI CTCAE (Common Terminology Criteria for Adverse Events) version 3.0 and were followed for 30 days after the date of withdrawal from study drug.

Outcome measures

Measure	Calcitriol + Cisplatin + Docetaxel n=31 Participants Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Number of Participants That Experience Grade 3 or Greater Neutropenia # of Phase 1 Participants w/ Grade 3+ Neutropenia	8 participants
Number of Participants That Experience Grade 3 or Greater Neutropenia # of Phase 2 Participants w/ Grade 3+ Neutropenia	9 participants

PRIMARY outcome

Timeframe: 5 years

Population: 22 patients were treated at the Maximum Tolerated Dose, including 6 phase I patients who received the MTD during the phase 1 component. 1 of 6 phase 1 patients was not evaluable due to toxicity. 1 patient (of 16) in the phase 2 study went to another therapy prior to the 30 day window and was excluded from analysis. 20 patients were analyzed.

The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, median time to progression was determined. Progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.

Outcome measures

Measure	Calcitriol + Cisplatin + Docetaxel n=20 Participants Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Median Time to Progression	5.8 months Interval 3.4 to 6.5

PRIMARY outcome

Timeframe: 5 years

Population: 22 patients were treated at the Maximum Tolerated Dose, including 6 phase I patients who received the MTD during the phase 1 component. 1 of 6 phase 1 patients was not evaluable due to toxicity. 1 patient (of 16) in the phase 2 study went to another therapy prior to the 30 day window and was excluded from analysis. 20 patients were analyzed.

The second primary objective was to characterize the toxicity and response of patients treated with a combination of calcitriol, cisplatin and docetaxel. To assess the response, overall survival was determined.

Outcome measures

Measure	Calcitriol + Cisplatin + Docetaxel n=20 Participants Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Median Overall Survival	8.7 months Interval 7.6 to 39.4

SECONDARY outcome

Timeframe: 12 and 24 hours post dose

Population: Patients from the phase II portion of the study were included in the pharmacokinetics analysis

The mean AUC (area under the curve) concentrations of 1,25-D3 from 0-12 hours and 0-24 hours will be calculated.

Outcome measures

Measure	Calcitriol + Cisplatin + Docetaxel n=16 Participants Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Mean AUC 1,25-D3 Concentration at 12 and 24 Hours AUC 0-12 Hours	15.95 h*ng/mL Standard Error 0.92
Mean AUC 1,25-D3 Concentration at 12 and 24 Hours AUC 0-24 Hours	31.74 h*ng/mL Standard Error 1.92

OTHER_PRE_SPECIFIED outcome

Timeframe: 3-6 months

Outcome measures

Outcome data not reported

Adverse Events

Calcitriol + Cisplatin + Docetaxel

Serious events: 20 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Measure	Calcitriol + Cisplatin + Docetaxel n=34 participants at risk Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Gastrointestinal disorders Abdominal Pain	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Blood and lymphatic system disorders Low Neutrophils/granulocytes (ANC/AGC)	5.9% 2/34 • Number of events 2 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Supraventricular and nodal arrhythmia	5.9% 2/34 • Number of events 2 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Hypotension	5.9% 2/34 • Number of events 2 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Colitis	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Dehydration	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Diarrhea	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Esophagitis	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Nausea	5.9% 2/34 • Number of events 2 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Vomiting	5.9% 2/34 • Number of events 2 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Respiratory, thoracic and mediastinal disorders Hemorrhage, pulmonary/upper respiratory	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Infections and infestations Febrile neutropenia	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Infections and infestations Lung Infection	5.9% 2/34 • Number of events 2 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Infections and infestations Upper Airway Infection	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Glomerular filtration rate	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Glucose, serum-low (hypoglycemia)	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Nervous system disorders Syncope (fainting)	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Musculoskeletal and connective tissue disorders Pain-Back	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Pain-Chest	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Vascular disorders Thrombosis/thrombus/embolism	2.9% 1/34 • Number of events 1 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.

Other adverse events

Measure	Calcitriol + Cisplatin + Docetaxel n=34 participants at risk Calcitriol, administered IV at 30, 45, 60, 80, or 100 mcg/m\^2 (every 21 days), along with Cisplatin, 75 mg/m\^2 (every three weeks), and Docetaxel, 75 mg/m\^2 (every three weeks).
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	11.8% 4/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Ear and labyrinth disorders Tinnitus	11.8% 4/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Blood and lymphatic system disorders Low Hemoglobin	41.2% 14/34 • Number of events 23 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Blood and lymphatic system disorders Low Leukocytes (total WBC)	41.2% 14/34 • Number of events 24 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Blood and lymphatic system disorders Lymphopenia	32.4% 11/34 • Number of events 24 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Blood and lymphatic system disorders Low Neutrophils/granulocytes (ANC/AGC)	41.2% 14/34 • Number of events 23 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Blood and lymphatic system disorders Low Platelets	23.5% 8/34 • Number of events 15 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Atrial fibrillation	8.8% 3/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Sinus tachycardia	11.8% 4/34 • Number of events 6 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Hypertension	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Hypotension	20.6% 7/34 • Number of events 10 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
General disorders Fatigue	50.0% 17/34 • Number of events 28 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
General disorders Fever	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Psychiatric disorders Insomnia	8.8% 3/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
General disorders Rigors/chills	11.8% 4/34 • Number of events 4 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Investigations Weight loss	11.8% 4/34 • Number of events 7 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Skin and subcutaneous tissue disorders Hair loss/alopecia (scalp or body)	14.7% 5/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Skin and subcutaneous tissue disorders Rash/desquamation	20.6% 7/34 • Number of events 7 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Anorexia	44.1% 15/34 • Number of events 17 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Constipation	20.6% 7/34 • Number of events 7 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Dehydration	17.6% 6/34 • Number of events 10 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Diarrhea	29.4% 10/34 • Number of events 15 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Dysphagia (difficulty swallowing)	8.8% 3/34 • Number of events 4 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Mucositis/stomatitis	20.6% 7/34 • Number of events 7 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Nausea	61.8% 21/34 • Number of events 29 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Taste alteration (dysgeusia)	26.5% 9/34 • Number of events 13 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Vomiting	35.3% 12/34 • Number of events 16 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Infections and infestations Febrile neutropenia	11.8% 4/34 • Number of events 4 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
General disorders Edema: limb	11.8% 4/34 • Number of events 7 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Elevated ALT, SGPT (serum glutamic pyruvic transaminase)	14.7% 5/34 • Number of events 15 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Elevated AST, SGOT(serum glutamic oxaloacetic transaminase)	26.5% 9/34 • Number of events 13 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	32.4% 11/34 • Number of events 15 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Elevated Alkaline phosphatase	20.6% 7/34 • Number of events 12 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Bilirubin (hyperbilirubinemia)	11.8% 4/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	20.6% 7/34 • Number of events 11 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Elevated Creatinine	11.8% 4/34 • Number of events 6 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	50.0% 17/34 • Number of events 42 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	11.8% 4/34 • Number of events 6 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Potassium, serum-high (hyperkalemia)	17.6% 6/34 • Number of events 6 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	17.6% 6/34 • Number of events 8 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Metabolism and nutrition disorders Sodium, serum-low (hyponatremia)	41.2% 14/34 • Number of events 20 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Musculoskeletal and connective tissue disorders Muscle weakness	14.7% 5/34 • Number of events 6 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Nervous system disorders Dizziness	20.6% 7/34 • Number of events 8 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Nervous system disorders Neuropathy: sensory	11.8% 4/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Eye disorders Vision-blurred vision	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Abdominal Pain	17.6% 6/34 • Number of events 10 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Musculoskeletal and connective tissue disorders Back Pain	20.6% 7/34 • Number of events 10 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Musculoskeletal and connective tissue disorders Bone Pain	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Cardiac disorders Chest Pain	8.8% 3/34 • Number of events 4 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Musculoskeletal and connective tissue disorders Limb Pain	8.8% 3/34 • Number of events 4 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Nervous system disorders Head Pain	14.7% 5/34 • Number of events 6 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
General disorders Pain NOS	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Gastrointestinal disorders Throat Pain	14.7% 5/34 • Number of events 5 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm, wheezing	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Respiratory, thoracic and mediastinal disorders Cough	26.5% 9/34 • Number of events 11 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Respiratory, thoracic and mediastinal disorders Dyspnea	23.5% 8/34 • Number of events 14 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.
Renal and urinary disorders Urinary retention	8.8% 3/34 • Number of events 3 • Adverse events were monitored from the start of study drug until 30 days after the date of withdrawal from study drug.

Additional Information

Dr. Nithya Ramnath

University of Michigan Comprehensive Cancer Center

Phone: 734-647-1417

Email: nithyar@umich.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place