Advanced AdenocarcinomaPhase 1/2NCT01506973
A Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane in Pancreatic Cancer
A Phase 1/2 study testing Hydroxychloroquine (HCQ), Gemcitabine and Abraxane in people with Advanced Adenocarcinoma and Metastatic Adenocarcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
In this Phase I/II clinical trial, the investigators seek to pilot the addition of Hydroxychloroquine (HCQ) to a commonly-used front-line therapy of pancreatic cancer, gemcitabine/nab-paclitaxel. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Adenocarcinoma, Metastatic Adenocarcinoma
- What is being tested?
- Hydroxychloroquine (HCQ), Gemcitabine and Abraxane
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 119 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Mar 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically documented advanced or metastatic adenocarcinoma of the pancreas.
- Patients must have measurable disease as defined by the RECIST criteria as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm with conventional techniques on either CT or MRI. Marker (CA19-9 or CEA) elevation alone is insufficient for entry.
- Patients may have had prior adjuvant treatment for pancreatic cancer. The last dose of chemotherapy must have been 4 months prior to study entry.
- Patients with prior radiotherapy are acceptable. It must be at least 4 months since administration of radiation therapy and all signs of toxicity must have abated.
- Patients must be age 18 years or older.
- Patients must have an ECOG performance status of 0-1.
Show all 16Show fewer
- The following required Initial Laboratory Values should be obtained within 4 weeks of the start of treatment:
- Granulocytes 1,500/ml
- Platelet Count 100,000/ml
- Creatinine 1.5 x upper limit of normal
- Bilirubin 1.5 x upper limit of normal
- AST 5 x upper limit of normal
- Patients must not be pregnant or lactating as chemotherapy is thought to present substantial risk to the fetus/infant.
- Patients must have an accessible primary tumor or metastasis, and be willing to have a pre-treatment and post-treatment tumor biopsy (at 6 to 8 weeks after beginning).
- Patients must have a life expectancy of greater than three months.
- Patients must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients may not be receiving any other investigational agents
- Known allergy to HCQ
- Patients with previous treatment with abraxane.
- Patients on therapeutic doses of Coumadin ( 1 mg daily). The use of therapeutic or prophylactic low molecular weight heparin or fragmin is permitted.
- Patients with known G6PD deficiency, severe psoriasis, porphyria, macular degeneration or severe diabetic retinopathy are ineligible because of the potential for greater HCQ toxicity.
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase I/II/Pharmacodynamic Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane to Inhibit Autophagy in Pancreatic Cancer
In this Phase I/II clinical trial, the investigators seek to pilot the addition of Hydroxychloroquine (HCQ) to a commonly-used front-line therapy of pancreatic cancer, gemcitabine/nab-paclitaxel. The investigators plan a run-in to define tolerable doses, and will explore doses of 800 and 1200 mg/day in successive cohorts of 6 patients. The investigators will assess toxicity continuously, and determine the dose for the Phase II trial based on standard toxicity criteria.
The correlative endpoints of this trial are directed to the pharmacokinetics of HCQ, and pharmacokinetic model of HCQ based on data from several ongoing trials, and the data from these patients will contribute to refining the model. The investigators will analyze both measured and model-predicted indices for their relationship to autophagy induction. Autophagy will be assessed as the accumulation of autophagocytic vesicles in the PMNs of treated patients, together with the induction of the expression of autophagy-related proteins on western analysis, quantitated by densitometry. The investigators will document the rates of metabolic response as a consequence of treatment, as a therapeutic marker that may be related to the degree of autophagy inhibition. Since the investigators have previously demonstrated a key role of JNK1 in the induction of autophagy by chemotherapy, the investigators will analyze archival tumor materials to determine variability in this marker, as a baseline for potential future trials. Finally, this study will incorporate metabolic profiling by mass spectrometry, which will be related to mutations (including Kras) in pretreatment tumor specimens. Mutational analysis will be accomplished by targeted sequencing or by next-generation sequencing, and the need for fresh tissue for all these endpoints will require patients to have a biopsy performed before treatment at at 6-8 weeks after beginning treatment. In the previous study of the Hh inhibitor GDC-0973 with the same chemotherapy, the investigators were able to obtain repeat biopsies successfully on all patients. The importance of these biopsies, to move the science forward in an era in which the tools now exist to provide meaningful correlative science, cannot be overstated.
Read the detailed description
Recent strategies have focused on improving the efficacy of gemcitabine either by improving the method of delivery, or by combining gemcitabine with other non-cross resistant agents. A sequence of Phase III combination studies of gemcitabine in combination (with oxaliplatin, and with the targeted therapies bevacizumab and cetuximab) have been negative, though based on strikingly positive Phase II data generated in cancer centers. Several studies suggest that taxanes are active in pancreatic cancer, but a randomized trial of gemcitabine with taxanes has not been preformed, probably on the basis that the differences in Phase II were insufficiently persuasive. The development of a novel taxane conjugate with albumin, abraxane, with established activity in breast cancer, prompted a Phase II trial of gemcitabine/abraxane by Von Hoff (6). Phase I/II data were highly promising, with response rates of the order of 40%, with tolerable toxicity, and a one-year survival of about 48%. A phase III trial of gemcitabine versus gemcitabine/abraxane is in progress, and based on these promising data has served as the control chemotherapy for previous SU2C trials. The development of a more intensive, but toxic regimen (FOLFIRINOX) in no way diminishes the enthusiasm for this chemotherapy backbone, given the activity in Phase II trials that appears comparable (7). Given the promise of this regimen, and the possibility of making a substantial improvement in outcome with additional targeted interventions, we propose to continue to use this regimen in the current study.
Of particular interest in extending these studies to pancreatic cancer is the finding that autophagy inhibition is particularly deleterious to cell lines bearing a mutant Kras protein. Additional studies as part of the SU2C pancreatic cancer project reveal that an autophagy program is activated in the presence of mutant Kras, and thus prompts the testing of this strategy in a setting in which Kras is commonly (about 85%) mutated (SU2C, unpublished data).
- Conditions
- Advanced Adenocarcinoma, Metastatic Adenocarcinoma
- Being tested
- Hydroxychloroquine (HCQ), Gemcitabine, Abraxane
- Keywords
- histologically or cytologically documented
- Medical subject headings
- Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine (HCQ)Drug
no other names
GemcitabineDrug
no other names
AbraxaneDrug
no other names
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine/Abraxane/Hydroxychloroquine | Experimental | Abraxane: 125mg/m2 IV infusion over 30 minutes on Days 1, 8, 15 Gemcitabine: 1000mg/m2 IV infusion over 30-100 minutes on Days 1, 8, 15 Hydroxychloroquine: 1200 mg/day PO daily (600mg BID) Daily from D1 Receives: Drug: Hydroxychloroquine (HCQ); Drug: Gemcitabine; Drug: Abraxane |
| Gemcitabine/Abraxane | Experimental | Abraxane: 125mg/m2 IV infusion over 30 minutes on Days 1, 8, 15 Gemcitabine: 1000mg/m2 IV infusion over 30-100 minutes on Days 1, 8, 15 Receives: Drug: Gemcitabine; Drug: Abraxane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2012 (estimated)
- Study startDec 2011
- Primary completionMar 2022
- Study completionMar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced AdenocarcinomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 119 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter O'Dwyer, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01506973
- Sponsor's protocol ID
- UPCC 19211
- Status last verified
- Jul 2025
- First submitted
- 3 Jan 2012
- Last updated
- 25 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Karasic TB, O'Hara MH, Loaiza-Bonilla A, Reiss KA, Teitelbaum UR, Borazanci E, De Jesus-Acosta A, Redlinger C, Burrell JA, Laheru DA, Von Hoff DD, Amaravadi RK, Drebin JA, O'Dwyer PJ. Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):993-998. doi: 10.1001/jamaoncol.2019.0684.
PubMed 31120501
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II/Pharmacodynamic Study of Hydroxychloroquine in Combination With Gemcitabine/Abraxane to Inhibit Autophagy in Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01506973
- Acronym / sponsor ID
- UPCC 19211
- Conditions
- Advanced Adenocarcinoma, Metastatic Adenocarcinoma
- Keywords
- histologically or cytologically documented
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 119 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Dec 2011
- Primary completion
- Mar 2022 (actual)
- Study completion
- Mar 2022 (actual)
- First posted
- 10 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this Phase I/II clinical trial, the investigators seek to pilot the addition of Hydroxychloroquine (HCQ) to a commonly-used front-line therapy of pancreatic cancer, gemcitabine/nab-paclitaxel. The investigators plan a run-in to define tolerable doses, and will explore doses of 800 and 1200 mg/day in successive cohorts of 6 patients. The investigators will assess toxicity continuously, and determine the dose for the Phase II trial based on standard toxicity criteria.
The correlative endpoints of this trial are directed to the pharmacokinetics of HCQ, and pharmacokinetic model of HCQ based on data from several ongoing trials, and the data from these patients will contribute to refining the model. The investigators will analyze both measured and model-predicted indices for their relationship to autophagy induction. Autophagy will be assessed as the accumulation of autophagocytic vesicles in the PMNs of treated patients, together with the induction of the expression of autophagy-related proteins on western analysis, quantitated by densitometry. The investigators will document the rates of metabolic response as a consequence of treatment, as a therapeutic marker that may be related to the degree of autophagy inhibition. Since the investigators have previously demonstrated a key role of JNK1 in the induction of autophagy by chemotherapy, the investigators will analyze archival tumor materials to determine variability in this marker, as a baseline for potential future trials. Finally, this study will incorporate metabolic profiling by mass spectrometry, which will be related to mutations (including Kras) in pretreatment tumor specimens. Mutational analysis will be accomplished by targeted sequencing or by next-generation sequencing, and the need for fresh tissue for all these endpoints will require patients to have a biopsy performed before treatment at at 6-8 weeks after beginning treatment. In the previous study of the Hh inhibitor GDC-0973 with the same chemotherapy, the investigators were able to obtain repeat biopsies successfully on all patients. The importance of these biopsies, to move the science forward in an era in which the tools now exist to provide meaningful correlative science, cannot be overstated.
Detailed description
Recent strategies have focused on improving the efficacy of gemcitabine either by improving the method of delivery, or by combining gemcitabine with other non-cross resistant agents. A sequence of Phase III combination studies of gemcitabine in combination (with oxaliplatin, and with the targeted therapies bevacizumab and cetuximab) have been negative, though based on strikingly positive Phase II data generated in cancer centers. Several studies suggest that taxanes are active in pancreatic cancer, but a randomized trial of gemcitabine with taxanes has not been preformed, probably on the basis that the differences in Phase II were insufficiently persuasive. The development of a novel taxane conjugate with albumin, abraxane, with established activity in breast cancer, prompted a Phase II trial of gemcitabine/abraxane by Von Hoff (6). Phase I/II data were highly promising, with response rates of the order of 40%, with tolerable toxicity, and a one-year survival of about 48%. A phase III trial of gemcitabine versus gemcitabine/abraxane is in progress, and based on these promising data has served as the control chemotherapy for previous SU2C trials. The development of a more intensive, but toxic regimen (FOLFIRINOX) in no way diminishes the enthusiasm for this chemotherapy backbone, given the activity in Phase II trials that appears comparable (7). Given the promise of this regimen, and the possibility of making a substantial improvement in outcome with additional targeted interventions, we propose to continue to use this regimen in the current study.
Of particular interest in extending these studies to pancreatic cancer is the finding that autophagy inhibition is particularly deleterious to cell lines bearing a mutant Kras protein. Additional studies as part of the SU2C pancreatic cancer project reveal that an autophagy program is activated in the presence of mutant Kras, and thus prompts the testing of this strategy in a setting in which Kras is commonly (about 85%) mutated (SU2C, unpublished data).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine/Abraxane/Hydroxychloroquine | Experimental | Drug: Hydroxychloroquine (HCQ), Drug: Gemcitabine, Drug: AbraxaneAbraxane: 125mg/m2 IV infusion over 30 minutes on Days 1, 8, 15 Gemcitabine: 1000mg/m2 IV infusion over 30-100 minutes on Days 1, 8, 15 Hydroxychloroquine: 1200 mg/day PO daily (600mg BID) Daily from D1 |
| Gemcitabine/Abraxane | Experimental | Drug: Gemcitabine, Drug: AbraxaneAbraxane: 125mg/m2 IV infusion over 30 minutes on Days 1, 8, 15 Gemcitabine: 1000mg/m2 IV infusion over 30-100 minutes on Days 1, 8, 15 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patients must have histologically or cytologically documented advanced or metastatic adenocarcinoma of the pancreas.
- Patients must have measurable disease as defined by the RECIST criteria as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm with conventional techniques on either CT or MRI. Marker (CA19-9 or CEA) elevation alone is insufficient for entry.
- Patients may have had prior adjuvant treatment for pancreatic cancer. The last dose of chemotherapy must have been 4 months prior to study entry.
- Patients with prior radiotherapy are acceptable. It must be at least 4 months since administration of radiation therapy and all signs of toxicity must have abated.
- Patients must be age 18 years or older.
Key exclusion criteria (5 listed)
- Patients may not be receiving any other investigational agents
- Known allergy to HCQ
- Patients with previous treatment with abraxane.
- Patients on therapeutic doses of Coumadin ( 1 mg daily). The use of therapeutic or prophylactic low molecular weight heparin or fragmin is permitted.
- Patients with known G6PD deficiency, severe psoriasis, porphyria, macular degeneration or severe diabetic retinopathy are ineligible because of the potential for greater HCQ toxicity.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxychloroquine (HCQ)no other names | Drug | Gemcitabine/Abraxane/Hydroxychloroquine |
| Gemcitabineno other names | Drug | Gemcitabine/Abraxane, Gemcitabine/Abraxane/Hydroxychloroquine |
| Abraxaneno other names | Drug | Gemcitabine/Abraxane, Gemcitabine/Abraxane/Hydroxychloroquine |
Primary outcome
Overall survival
Time frame: one year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
- Derived from this study: PubMed 31120501Karasic TB, O'Hara MH, Loaiza-Bonilla A, Reiss KA, Teitelbaum UR, Borazanci E, De Jesus-Acosta A, Redlinger C, Burrell JA, Laheru DA, Von Hoff DD, Amaravadi RK, Drebin JA, O'Dwyer PJ. Effect of Gemcitabine and nab-Paclitaxel With or Without Hydroxychloroquine on Patients With Advanced Pancreatic Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2019 Jul 1;5(7):993-998. doi: 10.1001/jamaoncol.2019.0684.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter O'Dwyer, MD principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hydroxychloroquine (HCQ), Gemcitabine and Abraxane in people with Advanced Adenocarcinoma and Metastatic Adenocarcinoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: one year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01506973, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025.