Solid TumorsPhase 1ESCALENCT01878890
Phase I Dose Escalation Trial of Efavirenz in Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
A Phase 1 study testing Efavirenz 600mg, Efavirenz 1200 mg and Efavirenz 1800 mg in people with Solid Tumors and Non-Hodgkin's Lymphoma, run by Institut Bergonié at 1 site in France.
Trial summary
Hypothesis: encouraging results of phase II study FAVE in the treatment of hormonal resistant prostate cancer lead us to continue clinical development of efavirenz. Furthermore, all available pre-clinical and clinical data lead us to conduct a Phase 1 study with efavirenz. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Solid Tumors, Non-Hodgkin's Lymphoma
- What is being tested?
- Efavirenz 600mg, Efavirenz 1200 mg and Efavirenz 1800 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- 5 Sep 2011to 31 Dec 2016
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with solid tumors (except pancreatic cancer) or non-Hodgkin lymphoma
- Metastatic disease or locally advanced inoperable tumor, not accessible to standard therapy.
- Male or female ≥ 18 years and <80 years.
- Tumor assessable by RECIST v1.1, Scher Cheson 2008 or 99.
- At least 28 days after completion of prior treatment (radiotherapy, systemic chemotherapy or major surgery).
- Patient who recovered from any prior toxicity ≤ grade 1.
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- WHO 0-1 in the 7 days before inclusion.
- Neutrophils ≥ 1500/mm3, Platelets ≥ 100 000/mm3.
- Total bilirubin and serum creatinine within normal limits (≤ 1.5 ULN), creatinine clearance ≥ 40 ml / min.
- AST / ALT ≤ 1.5 ULN (≤ 5 ULN if liver metastasis).
- Normal thyroid function.
- Normal coagulation: TP ≥ 70%.
- Life expectancy upper than 3 months.
- HAD score <13.
- Negative pregnancy test for women likely to be pregnant within 7 days before inclusion.
- Effective contraception for the duration of treatment (for both sexes in childbearing or reproductive age): mechanic contraception method should always be used in combination with other contraceptive methods (eg, oral or other hormonal contraceptives). Because of long half-life of efavirenz, it is recommended to use adequate contraceptive measures for 12 weeks after stopping treatment with efavirenz.
- Informed consent signed and dated by the patient or his legal representative before the establishment of any specific procedure to the study.
- Clinical examination and laboratory tests made within 7 days before enrollment and start of treatment.
- Initial assessment and radiological CT / or MRI performed within 30 days before enrollment.
- Patients potentially compliant with treatment and follow-up study.
- Ability to swallow capsules or tablets.
- Patients insured by a social security system.
Who cannot join
- Patient with pancreatic cancer.
- Presence of active or symptomatic cerebral localization (known).
- History of another cancer except:
- cancer occurred more than five years and considered in complete remission
- in situ cervix carcinomas,
- cutaneous basal cell carcinomas.
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- Current major depressive state (screening by HAD scale total score ≥ 13).
- Patients with history of depressive disorders, suicide attempts, addiction or other psychiatric disorders.
- Concomitant use of terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, alkaloids of ergot, voriconazole, mixing St. John's Wort.
- Patients treated with anti-vitamin K. Treatment with low molecular weight heparin are allowed.
- Known efavirenz hypersensitivity or to any of its excipients.
- Severe renal impairment.
- Severe hepatic impairment.
- Yellow fever vaccine (yellow fever).
- Pregnant or lactating.
- Presence of toxicity> 1 according to the criteria CTCAE V4.0, due to prior cancer therapy.
- Recurrent diarrhea which can interfere with drug absorption capacity.
- Patient included in another biomedical research on a drug within 30 days of inclusion.
- Patient who previously participated in this study.
- Patient, who for reasons psychological, psychiatric, social, family or geographical could not be treated or monitored regularly by the criteria of the study, patients deprived of liberty or under tutorship.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Dose Escalation Trial of Efavirenz for Patients With Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
Hypothesis: encouraging results of phase II study FAVE in the treatment of hormonal resistant prostate cancer lead us to continue clinical development of efavirenz. Furthermore, all available pre-clinical and clinical data lead us to conduct a Phase 1 study with efavirenz. Objective of this Phase I is to test doses above 600 mg / day in patients with cancer in order to determine the maximum tolerated dose to improve therapeutic effect.
This study is a single center Phase I trial, conduct with dose escalation scheme of efavirenz by continual reassessment method likehood approach (CRML) on solid tumours (except pancreatic cancer) and non-Hodgkin lymphoma (NHL).
Read more
Main objective is to determine the safety profile, and particularly the maximum tolerated dose of efavirenz for the treatment of patients with solid tumors (except pancreatic cancer) or NHL in therapeutic failure.
Secondary objectives are:
- Evaluate efavirenz pharmacokinetics at 2, 4 and 12 weeks;
- Evaluate objective response at 12 weeks;
- Evaluate progression free survival at 6 months;
- Assess biological progression-free survival at 6 months (prostate tumours only).
Primary Endpoint
Safety will be evaluated according to the toxicity scale NCI-CTCAE v4.0. Dose limiting toxicities will be collected during the first 28 days (+ / - 7 days) after first dose of Efavirenz and will be defined as follows:
- Any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade),
- Any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days,
- Score ≥ 19 HAD during treatment. Secondary Criteria
- Solid tumors: response and progression defined by RECIST v1.1 [Eisenhauer EA et al. EJC 2009).
- Non-Hodgkin lymphomas: Response and progression defined according to Cheson criteria [Cheson BD et al. JCO 1999]
- Biological progression (particular case of prostate tumors): defined according to Scher [Scher HI et al. JCO 2008] Statistical Considerations This is a Phase I dose escalation strategy using the method CRML, described by O'Quigley and Shen [O'Quigley et al. Biometrics 1996] and commonly used in Phase I trials in oncology.
- Maximum number of eligible and evaluable subjects is 30.
- Six dose levels are initially defined: 600 mg, 1200 mg, 1800 mg, 2200 mg, 2600 mg, 3000 mg.
- The risk of dose limiting toxicities maximum allowed is 25%.
Read the detailed description
This is a Phase I dose escalation strategy according to the method described by CRML O'Quigley and Shen [O'Quigley et al. Biometrics 1996] and commonly used in phase I trials in oncology.
Six levels of doses are initially defined: 600 mg, 1200 mg, 1800 mg, 2200 mg, 2600 mg, 3000 mg.
The maximum potential dose-limiting toxicities allowed is 25%.
Dose limiting toxicities will be defined as follows:
- Any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade),
- Any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days,
- Score ≥ 19 HAD during treatment.
- Conditions
- Solid Tumors, Non-Hodgkin's Lymphoma
- Being tested
- Efavirenz 600mg, Efavirenz 1200 mg, Efavirenz 1800 mg, Efavirenz 2200 mg
- Keywords
- Solid tumors (other than pancreas)
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efavirenz 600mgDrug
Efavirenz 600 mg (oral daily intake)
Efavirenz 1200 mgDrug
Efavirenz 1200mg (oral daily intake)
Efavirenz 1800 mgDrug
Efavirenz 1800mg (oral daily intake)
Efavirenz 2200 mgDrug
Efavirenz 2200mg (oral daily intake)
| Study group | Role | What they receive |
|---|---|---|
| Efavirenz: 600 mg | Experimental | Cohort 1 : Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity. Receives: Drug: Efavirenz 600mg |
| Efavirenz: 1200 mg | Experimental | Cohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity. Receives: Drug: Efavirenz 1200 mg |
| Efavirenz: 1800 mg | Experimental | Cohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity. Receives: Drug: Efavirenz 1800 mg |
| Efavirenz: 2200 mg | Experimental | Cohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity. Receives: Drug: Efavirenz 2200 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Efavirenz
MTD was determined by testing increasing doses up to 3000 mg (oral daily intake).
The dose escalation scheme is the continual reassessment method likehood approach (CRML) described by O'Quigley and Shen [O'Quigley et al. Biometrics 1996].
MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in > 25% of participants.
A DLT was any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade), any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.
Measured: Up to 28 days for each dosing cohort
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
A DLT was any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade), any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.
Measured: Up to 28 days for each dosing cohort
Secondary outcomes (2)
12-week Objective Response Rate
Objective response is defined as complete or partial response (CR, PR) using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Objective reponse rate is calculated as the number of patients with objective reponse divided by the number of alive patients.
Measured: up to 3 months after first adminitration of Efavirenz
12-week Non-progression Rate
Non progression is defined as complete or partial response (CR, PR) or stable disease (SD), using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Non-progression rate is calculated as the number of alive and progression free patients divided by the number of patients.
Measured: Evaluated up to 3 months after first administration of Efavirenz
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jun 2013 (estimated)
- Study start5 Sep 2011
- Primary completion16 Sep 2014
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Solid TumorsStudies of the same condition, open and under way.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Bergonié
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Guilhem Roubaud, MD, Study chair, Institut Bergonié
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01878890
- Sponsor's protocol ID
- IB2011-01
- Acronym
- ESCALE
- Status last verified
- Jan 2021
- First submitted
- 29 Oct 2012
- Last updated
- 27 Jan 2021
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Dose Escalation Trial of Efavirenz for Patients With Solid Tumours or Non-Hodgkin Lymphoma in Therapeutic Failure.
- ClinicalTrials.gov ID
- NCT01878890
- Acronym / sponsor ID
- ESCALE / IB2011-01
- Conditions
- Solid Tumors, Non-Hodgkin's Lymphoma
- Keywords
- Solid tumors (other than pancreas)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Institut BergoniéUniversity, hospital or other
- Study start
- 5 Sep 2011 (actual)
- Primary completion
- 16 Sep 2014 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 17 Jun 2013 (estimated)
- Results
- Posted 27 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypothesis: encouraging results of phase II study FAVE in the treatment of hormonal resistant prostate cancer lead us to continue clinical development of efavirenz. Furthermore, all available pre-clinical and clinical data lead us to conduct a Phase 1 study with efavirenz. Objective of this Phase I is to test doses above 600 mg / day in patients with cancer in order to determine the maximum tolerated dose to improve therapeutic effect.
This study is a single center Phase I trial, conduct with dose escalation scheme of efavirenz by continual reassessment method likehood approach (CRML) on solid tumours (except pancreatic cancer) and non-Hodgkin lymphoma (NHL).
Main objective is to determine the safety profile, and particularly the maximum tolerated dose of efavirenz for the treatment of patients with solid tumors (except pancreatic cancer) or NHL in therapeutic failure.
Secondary objectives are:
- Evaluate efavirenz pharmacokinetics at 2, 4 and 12 weeks;
- Evaluate objective response at 12 weeks;
- Evaluate progression free survival at 6 months;
- Assess biological progression-free survival at 6 months (prostate tumours only).
Primary Endpoint
Safety will be evaluated according to the toxicity scale NCI-CTCAE v4.0. Dose limiting toxicities will be collected during the first 28 days (+ / - 7 days) after first dose of Efavirenz and will be defined as follows:
- Any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade),
- Any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days,
- Score ≥ 19 HAD during treatment. Secondary Criteria
- Solid tumors: response and progression defined by RECIST v1.1 [Eisenhauer EA et al. EJC 2009).
- Non-Hodgkin lymphomas: Response and progression defined according to Cheson criteria [Cheson BD et al. JCO 1999]
- Biological progression (particular case of prostate tumors): defined according to Scher [Scher HI et al. JCO 2008] Statistical Considerations This is a Phase I dose escalation strategy using the method CRML, described by O'Quigley and Shen [O'Quigley et al. Biometrics 1996] and commonly used in Phase I trials in oncology.
- Maximum number of eligible and evaluable subjects is 30.
- Six dose levels are initially defined: 600 mg, 1200 mg, 1800 mg, 2200 mg, 2600 mg, 3000 mg.
- The risk of dose limiting toxicities maximum allowed is 25%.
Detailed description
This is a Phase I dose escalation strategy according to the method described by CRML O'Quigley and Shen [O'Quigley et al. Biometrics 1996] and commonly used in phase I trials in oncology.
Six levels of doses are initially defined: 600 mg, 1200 mg, 1800 mg, 2200 mg, 2600 mg, 3000 mg.
The maximum potential dose-limiting toxicities allowed is 25%.
Dose limiting toxicities will be defined as follows:
- Any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade),
- Any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days,
- Score ≥ 19 HAD during treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Efavirenz: 600 mg | Experimental | Drug: Efavirenz 600mgCohort 1 : Participants received 600 mg of Efavirenz (oral / once a day), until progression or toxicity. |
| Efavirenz: 1200 mg | Experimental | Drug: Efavirenz 1200 mgCohort 2 : Participants received 1200 mg of Efavirenz (oral / once a day), until progression or toxicity. |
| Efavirenz: 1800 mg | Experimental | Drug: Efavirenz 1800 mgCohort 3 : Participants received 1800 mg of Efavirenz (oral / once a day), until progression or toxicity. |
| Efavirenz: 2200 mg | Experimental | Drug: Efavirenz 2200 mgCohort 4 : Participants received 2200 mg of Efavirenz (oral / once a day), until progression or toxicity. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Patients with solid tumors (except pancreatic cancer) or non-Hodgkin lymphoma
- Metastatic disease or locally advanced inoperable tumor, not accessible to standard therapy.
- Male or female ≥ 18 years and <80 years.
- Tumor assessable by RECIST v1.1, Scher Cheson 2008 or 99.
- At least 28 days after completion of prior treatment (radiotherapy, systemic chemotherapy or major surgery).
Key exclusion criteria (20 listed)
- Patient with pancreatic cancer.
- Presence of active or symptomatic cerebral localization (known).
- History of another cancer except:
- Current major depressive state (screening by HAD scale total score ≥ 13).
- Patients with history of depressive disorders, suicide attempts, addiction or other psychiatric disorders.
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 |
|---|---|---|
| Efavirenz 600mgEfavirenz 600 mg (oral daily intake) | Drug | Efavirenz: 600 mg |
| Efavirenz 1200 mgEfavirenz 1200mg (oral daily intake) | Drug | Efavirenz: 1200 mg |
| Efavirenz 1800 mgEfavirenz 1800mg (oral daily intake) | Drug | Efavirenz: 1800 mg |
| Efavirenz 2200 mgEfavirenz 2200mg (oral daily intake) | Drug | Efavirenz: 2200 mg |
Primary outcome
Maximum Tolerated Dose (MTD) of Efavirenz
Time frame: Up to 28 days for each dosing cohort
MTD was determined by testing increasing doses up to 3000 mg (oral daily intake). The dose escalation scheme is the continual reassessment method likehood approach (CRML) described by O'Quigley and Shen [O'Quigley et al. Biometrics 1996]. MTD reflects the highest dose of drug that did not cause a Dose-Limiting Toxicity (DLT) in > 25% of participants. A DLT was any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade), any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
Time frame: Up to 28 days for each dosing cohort
A DLT was any drug-related toxicity with grade ≥ 3 according to NCI-CTCAE v4.0 (except alopecia, nausea and vomiting, regardless of grade), any drug-related toxicity, regardless of grade, who led a treatment delay> 14 days, a score ≥ 19 for the Hospital Anxiety And Depression Scale (HAD) during treatment.
2 secondary outcomes
12-week Objective Response Rate
Time frame: up to 3 months after first adminitration of Efavirenz
12-week Non-progression Rate
Time frame: Evaluated up to 3 months after first administration of Efavirenz
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Guilhem Roubaud, MD study chair
Institut Bergonié
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Efavirenz 600mg, Efavirenz 1200 mg and Efavirenz 1800 mg in people with Solid Tumors and Non-Hodgkin's Lymphoma, run by Institut Bergonié at 1 site in France.
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 22 inclusion and 20 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 27 Jan 2021. 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 France. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Maximum Tolerated Dose (MTD) of Efavirenz (time frame: Up to 28 days for each dosing cohort). 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 27 Jan 2021.