Trial Outcomes & Findings for Hydroxychloroquine, Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer (NCT NCT01006369)

Last Updated: 2021-09-21

Results Overview

Computed Kaplan-Meier survival curve estimates for progression free survival (PFS) and compared to historical controls of median PFS of 240 days. Evaluated response using RECIST criteria every 12 weeks.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

6 years

Results posted on

2021-09-21

Participant Flow

Subjects were recruited through the Rutgers Cancer Institute of New Jersey of New Jersey Oncology Group. The study was open to accrual on 05/8/2009 and terminated on 04/27/2016.

We are reporting results on 38 eligible patients. Nine patients were not eligible for participation.

Participant milestones

Participant milestones
Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily	XELOX + Bevacizumab + Hydroxychloroquine bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days XELOX regimen: Capecitabine will be started at a dose of 1,000 mg/m2/day bid po (total daily dose = 2,000 mg/m2) for 14 days (28 doses) of the 21 day cycle. This cycle will be repeated every 21 days. Oxaliplatin will be started at a dose of 130 mg/m2, in 250 ml of D5W over 2 hours given day 1 of each cycle. This cycle will be repeated every 21 days. hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Overall Study STARTED	13	25
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	12	25

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Hydroxychloroquine, Capecitabine, Oxaliplatin, and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine n=13 Participants bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily	XELOX + Bevacizumab + Hydroxychloroquine n=25 Participants bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days XELOX regimen: Capecitabine will be started at a dose of 1,000 mg/m2/day bid po (total daily dose = 2,000 mg/m2) for 14 days (28 doses) of the 21 day cycle. This cycle will be repeated every 21 days. Oxaliplatin will be started at a dose of 130 mg/m2, in 250 ml of D5W over 2 hours given day 1 of each cycle. This cycle will be repeated every 21 days. hydroxychloroquine: hydroxychloroquine 200 mg po BID daily	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Age, Categorical Between 18 and 65 years	11 Participants n=99 Participants	14 Participants n=107 Participants	25 Participants n=206 Participants
Age, Categorical >=65 years	2 Participants n=99 Participants	11 Participants n=107 Participants	13 Participants n=206 Participants
Sex: Female, Male Female	4 Participants n=99 Participants	12 Participants n=107 Participants	16 Participants n=206 Participants
Sex: Female, Male Male	9 Participants n=99 Participants	13 Participants n=107 Participants	22 Participants n=206 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants n=99 Participants	1 Participants n=107 Participants	3 Participants n=206 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=99 Participants	24 Participants n=107 Participants	35 Participants n=206 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	4 Participants n=107 Participants	6 Participants n=206 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	3 Participants n=107 Participants	3 Participants n=206 Participants
Race (NIH/OMB) White	11 Participants n=99 Participants	18 Participants n=107 Participants	29 Participants n=206 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants
Region of Enrollment United States	13 participants n=99 Participants	25 participants n=107 Participants	38 participants n=206 Participants

PRIMARY outcome

Timeframe: 6 years

Population: Subjects received FOLFOX6 or XELOX at physicians discretion with bevacizumab abd HCQ 200 mg po daily BID until progressive disease or intolerable side effects. Subjects were not analyzed by treatment assigned.

Outcome measures

Outcome measures
Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine n=38 Participants bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Progression-free Survival	424 days Interval 214.0 to 619.0

SECONDARY outcome

Timeframe: 6 years

Population: Subjects were assigned to FOLFOX6 or XELOX at physicians discretion and were analyzed as one group. Overall response rate was 75%

Response rate was evaluated every 12 weeks using RECIST criteria. CR+PR+Stable= overall response

Outcome measures

Outcome measures
Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine n=38 Participants bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Overall Response Rate	75 percentage of participants responding

SECONDARY outcome

Timeframe: 6 years

Population: Subjects were assigned to FOLFOX6 or XELOX at physician discretion and were analyzed together.

Computed using Kaplan-Meier survival curve estimates which were compared to historical controls (median overall survival) was 21.3 months (596).

Outcome measures

Outcome measures
Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine n=38 Participants bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Overall Survival	788 days Interval 652.0 to 788.0

Adverse Events

FOLFOX6 + Bevacizumab + Hydroxychloroquine

Serious events: 4 serious events

Other events: 13 other events

Deaths: 11 deaths

XELOX + Bevacizumab + Hydroxychloroquine

Serious events: 12 serious events

Other events: 25 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine n=13 participants at risk bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily	XELOX + Bevacizumab + Hydroxychloroquine n=25 participants at risk bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days XELOX regimen: Capecitabine will be started at a dose of 1,000 mg/m2/day bid po (total daily dose = 2,000 mg/m2) for 14 days (28 doses) of the 21 day cycle. This cycle will be repeated every 21 days. Oxaliplatin will be started at a dose of 130 mg/m2, in 250 ml of D5W over 2 hours given day 1 of each cycle. This cycle will be repeated every 21 days. hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Gastrointestinal disorders Dysphagia	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
General disorders Death	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
General disorders Allergic reaction/hypersensitivity	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Diarrhea	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	12.0% 3/25 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Obstruction, GI - colon	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Gastrointestinal - other (specific)	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Dehydration	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Nervous system disorders Neuropathy: motor	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
General disorders Pain - chest wall	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders Potassium, serum low	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	0.00% 0/25 • Adverse events were collected over a period of 128 days per patient.

Other adverse events

Additional Information

Elizabeth Poplin MD

Rutgers Cancer Institute of New Jersey

Phone: 732-235-7620

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	FOLFOX6 + Bevacizumab + Hydroxychloroquine n=13 participants at risk bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days hydroxychloroquine: hydroxychloroquine 200 mg po BID daily	XELOX + Bevacizumab + Hydroxychloroquine n=25 participants at risk bevacizumab: Arm A: FOLFOX6 + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 5 mg/kg in 100 cc Normal Saline every 14 days on day one Arm B: XELOX + Bevacizumab + Hydroxychloroquine: Bevacizumab will be administered intravenously 7.5 mg/kg in 100 cc Normal Saline every 21 days XELOX regimen: Capecitabine will be started at a dose of 1,000 mg/m2/day bid po (total daily dose = 2,000 mg/m2) for 14 days (28 doses) of the 21 day cycle. This cycle will be repeated every 21 days. Oxaliplatin will be started at a dose of 130 mg/m2, in 250 ml of D5W over 2 hours given day 1 of each cycle. This cycle will be repeated every 21 days. hydroxychloroquine: hydroxychloroquine 200 mg po BID daily
Blood and lymphatic system disorders Decreased hemoglobin	30.8% 4/13 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.	36.0% 9/25 • Number of events 9 • Adverse events were collected over a period of 128 days per patient.
Blood and lymphatic system disorders Hemolysis	15.4% 2/13 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.	0.00% 0/25 • Adverse events were collected over a period of 128 days per patient.
Blood and lymphatic system disorders Leukocytes (total WBC)	15.4% 2/13 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Blood and lymphatic system disorders Lymphopenia	30.8% 4/13 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
Blood and lymphatic system disorders Neutrophils/granulocytes (ANC/AGC)	100.0% 13/13 • Number of events 32 • Adverse events were collected over a period of 128 days per patient.	40.0% 10/25 • Number of events 10 • Adverse events were collected over a period of 128 days per patient.
Blood and lymphatic system disorders Platelets	30.8% 4/13 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
Cardiac disorders Hypertension	23.1% 3/13 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
General disorders Insomnia	15.4% 2/13 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
General disorders Fatigue	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	64.0% 16/25 • Number of events 16 • Adverse events were collected over a period of 128 days per patient.
General disorders Fever	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
General disorders Weight loss	15.4% 2/13 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.	12.0% 3/25 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	0.00% 0/25 • Adverse events were collected over a period of 128 days per patient.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Skin and subcutaneous tissue disorders Rash: hand-foot skin reaction	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	32.0% 8/25 • Number of events 8 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Anorexia	23.1% 3/13 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Constipation	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	20.0% 5/25 • Number of events 5 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Diarrhea	15.4% 2/13 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.	68.0% 17/25 • Number of events 17 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Dysphagia	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Nausea	23.1% 3/13 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.	36.0% 9/25 • Number of events 9 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Dehydration	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Mucositis/stomatitis - oral cavity	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	12.0% 3/25 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.
Gastrointestinal disorders Vomiting	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	28.0% 7/25 • Number of events 7 • Adverse events were collected over a period of 128 days per patient.
Blood and lymphatic system disorders Hemorrhage, pulmonary upper respiratory - nose	15.4% 2/13 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders Potassium, serum low (hypokalemia)	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	12.0% 3/25 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders ALT, SGPT	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	12.0% 3/25 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders AST, SGOT	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders Albumin, serum low	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders Glucose, serum high	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	16.0% 4/25 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.
Metabolism and nutrition disorders Lipase	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Nervous system disorders Mood alteration - depression	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	0.00% 0/25 • Adverse events were collected over a period of 128 days per patient.
Nervous system disorders Neurology - motor	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	4.0% 1/25 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.
Nervous system disorders Neuropathy - sensory	30.8% 4/13 • Number of events 4 • Adverse events were collected over a period of 128 days per patient.	96.0% 24/25 • Number of events 24 • Adverse events were collected over a period of 128 days per patient.
General disorders Pain	46.2% 6/13 • Number of events 6 • Adverse events were collected over a period of 128 days per patient.	12.0% 3/25 • Number of events 3 • Adverse events were collected over a period of 128 days per patient.
Vascular disorders Thrombosis	7.7% 1/13 • Number of events 1 • Adverse events were collected over a period of 128 days per patient.	0.00% 0/25 • Adverse events were collected over a period of 128 days per patient.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/13 • Adverse events were collected over a period of 128 days per patient.	8.0% 2/25 • Number of events 2 • Adverse events were collected over a period of 128 days per patient.