Trial Outcomes & Findings for 68Ga-THP-PSMA PET/CT Imaging in High Risk Primary Prostate Cancer or Biochemical Recurrence of Prostate Cancer (NCT NCT03617588)

Last Updated: 2020-06-24

Results Overview

The impact of 68Ga-THP-PSMA PET/CT on the management of patients with PCa was analysed by measuring the percentage of patients who had a change in management plan as a result of 68Ga-THP-PSMA PET/CT documented after scan, compared with their pre-scan management plan. A change status of 'Yes' was assigned if there was any difference in treatment options between the intended and revised management plans. A change status of 'No' was assigned if the intended and revised management plans remained identical. This endpoint was assessed in the full analysis set, but as a sensitivity analysis, was also assessed in the per protocol population in case there was a difference between the populations. As all 49 patients underwent a technically successful post-baseline scan, the full analysis set and per protocol populations were the same.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

49 participants

Primary outcome timeframe

up to 3 months post PET/CT

Results posted on

2020-06-24

Participant Flow

Recruitment Period June 18th 2018 to June 12th 2019.

Participant milestones

Participant milestones
Measure	Group A Patients with newly diagnosed primary high-risk PCa who were scheduled for RP surgery.	Groups B and C Group B: Patients with PCa and a diagnosis of BCR, previously treated with RP and being considered for radical salvage therapy (with curative intent). Group C: Patients with PCa and a diagnosis of BCR, previously treated with radical radiotherapy and being considered for radical salvage therapy (with curative intent).
Overall Study STARTED	20	29
Overall Study COMPLETED	19	29
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A Patients with newly diagnosed primary high-risk PCa who were scheduled for RP surgery.	Groups B and C Group B: Patients with PCa and a diagnosis of BCR, previously treated with RP and being considered for radical salvage therapy (with curative intent). Group C: Patients with PCa and a diagnosis of BCR, previously treated with radical radiotherapy and being considered for radical salvage therapy (with curative intent).
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

68Ga-THP-PSMA PET/CT Imaging in High Risk Primary Prostate Cancer or Biochemical Recurrence of Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=20 Participants Patients with newly diagnosed primary high-risk PCa who were scheduled for RP surgery.	Groups B and C n=29 Participants Group B: Patients with PCa and a diagnosis of BCR, previously treated with RP and being considered for radical salvage therapy (with curative intent). Group C: Patients with PCa and a diagnosis of BCR, previously treated with radical radiotherapy and being considered for radical salvage therapy (with curative intent).	Total n=49 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	14 Participants n=7 Participants	22 Participants n=5 Participants
Age, Categorical >=65 years	12 Participants n=5 Participants	15 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	29 Participants n=7 Participants	49 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	21 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United Kingdom	20 participants n=5 Participants	29 participants n=7 Participants	49 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 3 months post PET/CT

Population: Subject analysis set title: Safety Evaluable Population Subject analysis set type: Safety analysis Subject analysis set description: All patients who received a 68Ga-THP-PSMA PET/CT dose, regardless of whether they received the full intended dose, or proceeded to undergo the intended 68Ga-THP-PSMA PET/CT scan.

Outcome measures

Outcome measures
Measure	Group A n=20 Participants Patients with newly diagnosed primary high-risk PCa who were scheduled for RP surgery.	Groups B and C n=29 Participants Group B: Patients with PCa and a diagnosis of BCR, previously treated with RP and being considered for radical salvage therapy (with curative intent). Group C: Patients with PCa and a diagnosis of BCR, previously treated with radical radiotherapy and being considered for radical salvage therapy (with curative intent).	Full Analysis Set n=49 Participants A subset of the safety population who underwent the Visit 2 68Ga-THP-PSMA PET/CT scan, regardless of whether the scan was a technical success or failure.	Per Protocol Set n=49 Participants A subset of the Full Analysis Set with at least one technically successful post baseline 68Ga-THP-PSMA PET/CT scan and without any major protocol deviations.
Change in Patient Management change in management plan	6 Participants	15 Participants	21 Participants	21 Participants
Change in Patient Management no change in management plan	14 Participants	14 Participants	28 Participants	28 Participants

SECONDARY outcome

Timeframe: Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA.

Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.

Outcome measures

Outcome measures
Measure	Group A n=20 Participants Patients with newly diagnosed primary high-risk PCa who were scheduled for RP surgery.	Groups B and C n=29 Participants Group B: Patients with PCa and a diagnosis of BCR, previously treated with RP and being considered for radical salvage therapy (with curative intent). Group C: Patients with PCa and a diagnosis of BCR, previously treated with radical radiotherapy and being considered for radical salvage therapy (with curative intent).	Full Analysis Set n=49 Participants A subset of the safety population who underwent the Visit 2 68Ga-THP-PSMA PET/CT scan, regardless of whether the scan was a technical success or failure.	Per Protocol Set A subset of the Full Analysis Set with at least one technically successful post baseline 68Ga-THP-PSMA PET/CT scan and without any major protocol deviations.
Safety - Treatment Emergent Adverse Events Any serious TEAE	0 number of subjects	0 number of subjects	0 number of subjects	—
Safety - Treatment Emergent Adverse Events Any serious TEAE related to 68Ga-THP-PSMA	0 number of subjects	0 number of subjects	0 number of subjects	—
Safety - Treatment Emergent Adverse Events Any TEAE leading to discontinuation from study	0 number of subjects	0 number of subjects	0 number of subjects	—
Safety - Treatment Emergent Adverse Events Any related TEAE leading to discontinuation	0 number of subjects	0 number of subjects	0 number of subjects	—
Safety - Treatment Emergent Adverse Events Any TEAE	2 number of subjects	3 number of subjects	5 number of subjects	—
Safety - Treatment Emergent Adverse Events Any TEAE related to 68Ga-THP-PSMA	1 number of subjects	1 number of subjects	2 number of subjects	—
Safety - Treatment Emergent Adverse Events Any TEAE CTCAE Grade 3 or higher	1 number of subjects	1 number of subjects	2 number of subjects	—
Safety - Treatment Emergent Adverse Events Any related TEAE CTCAE Grade 3 or higher	0 number of subjects	0 number of subjects	0 number of subjects	—
Safety - Treatment Emergent Adverse Events Any TEAE with outcome of death	0 number of subjects	0 number of subjects	0 number of subjects	—
Safety - Treatment Emergent Adverse Events Any related TEAE with outcome of death	0 number of subjects	0 number of subjects	0 number of subjects	—

Adverse Events

Group A

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Groups B and C

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Safety Evaluable Population

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Group A n=20 participants at risk Patients with newly diagnosed primary high-risk PCa who were scheduled for RP surgery.	Groups B and C n=29 participants at risk Group B: Patients with PCa and a diagnosis of BCR, previously treated with RP and being considered for radical salvage therapy (with curative intent). Group C: Patients with PCa and a diagnosis of BCR, previously treated with radical radiotherapy and being considered for radical salvage therapy (with curative intent).	Safety Evaluable Population n=49 participants at risk All patients who received a 68Ga-THP-PSMA PET/CT dose, regardless of whether they received the full intended dose, or proceeded to undergo the intended 68Ga-THP-PSMA PET/CT scan.
Injury, poisoning and procedural complications Thermal Burn	0.00% 0/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	3.4% 1/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Cardiac disorders Palpitations	0.00% 0/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	3.4% 1/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Nervous system disorders Syncope	5.0% 1/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	0.00% 0/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Nervous system disorders Dizziness	0.00% 0/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	3.4% 1/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Nervous system disorders Sensory loss	0.00% 0/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	3.4% 1/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
General disorders Catheter site rash	0.00% 0/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	3.4% 1/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Psychiatric disorders Confusional state	5.0% 1/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	0.00% 0/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Gastrointestinal disorders Vomiting	5.0% 1/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	0.00% 0/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Skin and subcutaneous tissue disorders Pruritis	5.0% 1/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	0.00% 0/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/20 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	3.4% 1/29 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.	2.0% 1/49 • Safety was assessed at screening, during the study and at Visit 4. AEs, regardless of relationship to study treatment, were recorded from the time of 68Ga-THP-PSMA administration until 30 days after the administration of 68Ga-THP-PSMA. Safety was assessed by means of physical examination, vital signs, cardiovascular profile, performance status, laboratory evaluations (haematology, biochemistry, urinalysis and prostate-specific antigen), recording of concurrent illness/therapy and AEs. No dose limiting toxicity was defined in this study.

Additional Information

Director of Clinical Operations

Theragnostics Ltd

Phone: +44 330 606 7437

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place