Breast CancerPhase 1/2GLACIERNCT03400254
Gedatolisib, Hydroxychloroquine or the Combination for Prevention of Recurrent Breast Cancer ("GLACIER")
A Phase 1/2 study testing Hydroxychloroquine (HCQ) and Gedatolisib in people with Breast Cancer, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial summary
This clinical trial will assess the safety and early efficacy of the role of gedatolisib and hydroxychloroquine in early-stage breast cancer patients with residual disease and evidence of disseminated tumor cells (DTCs) on bone marrow aspirate after neoadjuvant chemotherapy (NACT) and definitive surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Hydroxychloroquine (HCQ) and Gedatolisib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Feb 2019to 12 Nov 2019
- 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
- -Bone marrow aspirate after completion of neoadjuvant chemotherapy and surgery demonstrates detectable DTCs (via IHC) as performed by central laboratory assessment at Univerity of Pennsylvania.
- NOTE: The criterion will be assessed AFTER confirmation of the eligibility criteria below. Patients must be pre-registered for screening of DTCs as outlined in Section 5.1 History of stage I-III histologically-confirmed primary invasive breast cancer with no evidence of recurrent local or distant disease. NOTE: Patients with bilateral breast cancer are eligible, so long as both cancers are treated with curative intent.
- Any receptor status at diagnosis (by ASCO/CAP guidelines) is eligible; however, the following criteria apply:
- Patients with ER+/Her2 negative tumors must have demonstrated pathologic residual invasive disease within either the breast (with residual tumor measuring ≥ 2.5 cm) or regional lymph nodes at the time of definitive surgery following neoadjuvant therapy.
- Patients with Her2+ disease (regardless of ER status) or triple negative (ER-/PR-/Her2-) disease are eligible if there is any amount of residual disease present in the breast or regional lymph nodes at the time of definitive surgery following neoadjuvant therapy.
- Prior Treatment:
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- Patients must have received neoadjuvant chemotherapy prior to surgery.
- Patients must be within 24 months of undergoing definitive breast surgery post-neoadjuvant therapy. All margins of resection must be free of disease at the time of final surgical treatment.
- Patients must have completed adjuvant treatment, including post-surgery chemotherapy (if clinically indicated), radiation (if clinically indicated) and/or Her2-directed adjuvant therapy (if Her2+). Prior treatment-related toxicity must be resolved to ≤ Grade 1 with the exception of alopecia and peripheral neuropathy, prior to study enrollment..
- Current/Concurrent Treatment:
- Concurrent receipt of endocrine adjuvant therapy is allowed only if therapy consists of an aromatase
- Patients will be eligible to enroll after receiving a minimum of 3 months of adjuvant endocrine therapy, to allow stabilization of side effects. Premenopausal patients on concurrent ovarian suppression are eligible. Patients on tamoxifen are ineligible due to the potential drug-drug interaction with hydroxychloroquine. Patients on any other adjuvant endocrine therapy, including any investigational therapy, are ineligible.
- Concurrent receipt of bone modifying agents (bisphosphonates or rank-ligand inhibitors) is allowed.
- No concurrent enrollment on another investigational therapy clinical trial.
- No prior therapy with a PI3Kinase inhibitor or mTOR inhibitor.
- Men and women, age ≥ 18 years.
- No contraindications to the study medications or uncontrolled medical illness.
- Adequate bone marrow, liver, and renal function and other parameters as follows:
- ANC ≥ 1.5 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin > 9 g/dL
- Serum bilirubin ≤ 1.5 x ULN
- ALT and AST ≤ 2.5 x ULN
- Serum creatinine ≤ 2.0 x ULN or creatinine clearance (CrCl) ≥ 30mL/min obtained within 30 days prior to registration. A calculated creatinine clearance by Cockcroft-Gault Formula is acceptable in lieu of a measured value.
- Normal coagulation studies: PT and PTT ≤ 1.5 x upper limit of normal per institutional laboratory range
- Ability to provide informed consent.
- Ability to speak and understand English
Who cannot join
- Patients with a history of another prior invasive breast cancer are ineligible. Patients with prior DCIS of the breast are eligible if this was diagnosed > 5 years prior to enrollment. Patients with prior invasive malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment.
- Any severe and/or uncontrolled medical conditions or other conditions that could affect subject participation in the study including:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- Unstable angina pectoris, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- Severely impaired lung function with a previously documented spirometry and DLCO that is 50% of the normal predicted value (these tests not required at screening; prior results, if performed for standard of care should be referenced) and/or O2 saturation that is 88% or less at rest on room air
- Uncontrolled diabetes
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- Active (acute or chronic) or uncontrolled severe infections
- Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis A known history of HIV seropositivity as reported by the patient. HIV testing is not required.
- Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of hydroxychloroquine (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
- Patients with an active, bleeding diathesis. Patients receiving therapeutic anticoagulation are not eligible for study participation.
- Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. If barrier contraceptives are being used, these must be continued throughout the trial and for 8 weeks after stopping study drug, by both sexes. Hormonal contraceptives are not acceptable as a sole method of contraception. (Women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of Gedatolisib). Inclusion of Underrepresented Populations Individuals of all races and ethnic groups are eligible for this trial. There is no bias towards age or gender.
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 Ib/II Trial of Gedatolisib, Hydroxychloroquine or the Combination for Prevention of Recurrent Breast Cancer ("GLACIER")
This clinical trial will assess the safety and early efficacy of the role of gedatolisib and hydroxychloroquine in early-stage breast cancer patients with residual disease and evidence of disseminated tumor cells (DTCs) on bone marrow aspirate after neoadjuvant chemotherapy (NACT) and definitive surgery.
- Conditions
- Breast Cancer
- Being tested
- Hydroxychloroquine (HCQ), Gedatolisib
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxychloroquine (HCQ)Drug
All patients will receive HCQ at a dose of 600 mg orally twice daily. This dose is the same in both phase Ib and phase II portions of the protocol. Capsules of HCQ are available in 200 mg strength, thus patients will initially start with 3 capsules twice daily for a total of 6 capsules per day. HCQ will be administered in divided doses (BID). When taking HCQ twice daily, the two daily doses should be taken 12 hours apart as close to 9am and 9pm as possible. Patients receiving antacids, sucralfate, cholestyramine, and/or bicarbonate should have the HCQ drug dose administered at least 1 hour before or 2 hours after these medications. Hydroxychloroquine will be obtained from the UPENN Investigational Drug Service (IDS).
GedatolisibDrug
Gedatolisib will be administered intravenously on a weekly dosing schedule at 150 mg IV.
Within 3 days prior to GED dosing the patient must have an ANC >1.0 x 109/L and platelet count > 75 x 109/L. If hematologic toxicity persists, treatment should be delayed by one week and the complete blood cell count with differential and platelet count repeated. Treatment may be delayed for up to 4 consecutive weeks (28 days). If after 28 days of delay all hematologic toxicity has still not resolved to normal and non-hematologic toxicity has not resolved to <grade 1 then any further treatment with GED should be stopped.
| Study group | Role | What they receive |
|---|---|---|
| Phase II: Arm A | Experimental | Patients will receive HCQ, 600 mg BID, for 24 weeks. Receives: Drug: Hydroxychloroquine (HCQ); Drug: Gedatolisib |
| Phase II: Arm B | Experimental | Patients will receive HCQ, 600 mg BID, for 24 weeks and GED x 2 weeks administered weekly, as an intravenous dose of 150 mg. Receives: Drug: Hydroxychloroquine (HCQ); Drug: Gedatolisib |
| Phase II: Arm C | Experimental | Patients will receive HCQ, 600 mg BID, for 24 weeks and GED x 6 weeks administered weekly, as an intravenous dose of 150 mg. Receives: Drug: Hydroxychloroquine (HCQ); Drug: Gedatolisib |
| Phase II: Arm D | Experimental | Patients will receive HCQ, 600 mg BID, for 24 weeks and GED x 12 weeks administered weekly, as an intravenous dose of 150 mg. Receives: Drug: Hydroxychloroquine (HCQ); Drug: Gedatolisib |
| Phase Ib Arm | Experimental | Patients will receive HCQ, 600 mg BID, and GED, administered weekly as an intravenous dose of 150 mg, for 6 weeks. Receives: Drug: Hydroxychloroquine (HCQ); Drug: Gedatolisib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of Adverse Events
Frequency of 'a priori' defined "severe" adverse events and any adverse event by NCI CTCAE v5 criteria (Phase Ib)
Measured: Approximately 4 Years
Response to Treatment
"Response" to treatment is defined by a greater than or equal to 50% reduction in number of disseminated tumor cells (DTCs) at 24 weeks compared to baseline (Phase II)
Measured: Approximately 6 Months
Secondary outcomes (2)
Occurrence of Adverse Events
NCI CTCAE v5 criteria (Phase II)
Measured: Approximately 6 Months
Recurrence After Treatment
Recurrence Free Survival (RFS)
Measured: 3 Years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start26 Feb 2019
- Primary completion30 Aug 2019
- Study completion12 Nov 2019
Why it stopped: due to business decision regarding the study drug.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies 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
- Single group
- Model description
- 24 participants in Phase Ib and 80 participants in Phase II
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium, Pfizer, Hoosier Cancer Research Network, Breast Cancer Research Foundation
- Responsible party
- Sponsor
- Investigators
- Angela DeMichele, MD, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03400254
- Sponsor's protocol ID
- UPCC 10117
- Acronym
- GLACIER
- Status last verified
- Apr 2020
- First submitted
- 11 Jan 2018
- Last updated
- 28 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib/II Trial of Gedatolisib, Hydroxychloroquine or the Combination for Prevention of Recurrent Breast Cancer ("GLACIER")
- ClinicalTrials.gov ID
- NCT03400254
- Acronym / sponsor ID
- GLACIER / UPCC 10117
- Conditions
- Breast Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: due to business decision regarding the study drug.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium, Pfizer, Hoosier Cancer Research Network, Breast Cancer Research Foundation
- Study start
- 26 Feb 2019 (actual)
- Primary completion
- 30 Aug 2019 (actual)
- Study completion
- 12 Nov 2019 (actual)
- First posted
- 17 Jan 2018 (actual)
- 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.
This clinical trial will assess the safety and early efficacy of the role of gedatolisib and hydroxychloroquine in early-stage breast cancer patients with residual disease and evidence of disseminated tumor cells (DTCs) on bone marrow aspirate after neoadjuvant chemotherapy (NACT) and definitive surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 5
- Model description
- 24 participants in Phase Ib and 80 participants in Phase II
| Arm | Type | Receives |
|---|---|---|
| Phase II: Arm A | Experimental | Drug: Hydroxychloroquine (HCQ), Drug: GedatolisibPatients will receive HCQ, 600 mg BID, for 24 weeks. |
| Phase II: Arm B | Experimental | Drug: Hydroxychloroquine (HCQ), Drug: GedatolisibPatients will receive HCQ, 600 mg BID, for 24 weeks and GED x 2 weeks administered weekly, as an intravenous dose of 150 mg. |
| Phase II: Arm C | Experimental | Drug: Hydroxychloroquine (HCQ), Drug: GedatolisibPatients will receive HCQ, 600 mg BID, for 24 weeks and GED x 6 weeks administered weekly, as an intravenous dose of 150 mg. |
| Phase II: Arm D | Experimental | Drug: Hydroxychloroquine (HCQ), Drug: GedatolisibPatients will receive HCQ, 600 mg BID, for 24 weeks and GED x 12 weeks administered weekly, as an intravenous dose of 150 mg. |
| Phase Ib Arm | Experimental | Drug: Hydroxychloroquine (HCQ), Drug: GedatolisibPatients will receive HCQ, 600 mg BID, and GED, administered weekly as an intravenous dose of 150 mg, for 6 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- -Bone marrow aspirate after completion of neoadjuvant chemotherapy and surgery demonstrates detectable DTCs (via IHC) as performed by central laboratory assessment at Univerity of Pennsylvania.
- NOTE: The criterion will be assessed AFTER confirmation of the eligibility criteria below. Patients must be pre-registered for screening of DTCs as outlined in Section 5.1 History of stage I-III histologically-confirmed primary invasive breast cancer with no evidence of recurrent local or distant disease. NOTE: Patients with bilateral breast cancer are eligible, so long as both cancers are treated with curative intent.
- Any receptor status at diagnosis (by ASCO/CAP guidelines) is eligible; however, the following criteria apply:
- Patients with ER+/Her2 negative tumors must have demonstrated pathologic residual invasive disease within either the breast (with residual tumor measuring ≥ 2.5 cm) or regional lymph nodes at the time of definitive surgery following neoadjuvant therapy.
- Patients with Her2+ disease (regardless of ER status) or triple negative (ER-/PR-/Her2-) disease are eligible if there is any amount of residual disease present in the breast or regional lymph nodes at the time of definitive surgery following neoadjuvant therapy.
Key exclusion criteria (11 listed)
- Patients with a history of another prior invasive breast cancer are ineligible. Patients with prior DCIS of the breast are eligible if this was diagnosed > 5 years prior to enrollment. Patients with prior invasive malignancy other than breast cancer are eligible if they have been disease-free for at least 5 years prior to enrollment.
- Any severe and/or uncontrolled medical conditions or other conditions that could affect subject participation in the study including:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- Unstable angina pectoris, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- Severely impaired lung function with a previously documented spirometry and DLCO that is 50% of the normal predicted value (these tests not required at screening; prior results, if performed for standard of care should be referenced) and/or O2 saturation that is 88% or less at rest on room air
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)All patients will receive HCQ at a dose of 600 mg orally twice daily. This dose is the same in both phase Ib and phase II portions of the protocol. Capsules of HCQ are available in 200 mg strength, thus patients will initially start with 3 capsules twice daily for a total of 6 capsules per day. HCQ will be administered in divided doses (BID). When taking HCQ twice daily, the two daily doses should be taken 12 hours apart as close to 9am and 9pm as possible. Patients receiving antacids, sucralfate, cholestyramine, and/or bicarbonate should have the HCQ drug dose administered at least 1 hour before or 2 hours after these medications. Hydroxychloroquine will be obtained from the UPENN Investigational Drug Service (IDS). | Drug | Phase II: Arm A, Phase II: Arm B, Phase II: Arm C, Phase II: Arm D, Phase Ib Arm |
| GedatolisibGedatolisib will be administered intravenously on a weekly dosing schedule at 150 mg IV. Within 3 days prior to GED dosing the patient must have an ANC >1.0 x 109/L and platelet count > 75 x 109/L. If hematologic toxicity persists, treatment should be delayed by one week and the complete blood cell count with differential and platelet count repeated. Treatment may be delayed for up to 4 consecutive weeks (28 days). If after 28 days of delay all hematologic toxicity has still not resolved to normal and non-hematologic toxicity has not resolved to <grade 1 then any further treatment with GED should be stopped. | Drug | Phase II: Arm A, Phase II: Arm B, Phase II: Arm C, Phase II: Arm D, Phase Ib Arm |
Primary outcome
Frequency of Adverse Events
Time frame: Approximately 4 Years
Frequency of 'a priori' defined "severe" adverse events and any adverse event by NCI CTCAE v5 criteria (Phase Ib)
Response to Treatment
Time frame: Approximately 6 Months
"Response" to treatment is defined by a greater than or equal to 50% reduction in number of disseminated tumor cells (DTCs) at 24 weeks compared to baseline (Phase II)
2 secondary outcomes
Occurrence of Adverse Events
Time frame: Approximately 6 Months
Recurrence After Treatment
Time frame: 3 Years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2020.
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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.
Angela DeMichele, 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) and Gedatolisib in people with Breast Cancer, 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 27 inclusion and 11 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: withdrawn, as of the sponsor's last update on 28 Apr 2020. 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 was withdrawn before enrolling participants, so there are no results.
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?
Frequency of Adverse Events (time frame: Approximately 4 Years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2020.