Photodynamic Therapy and Vismodegib for Multiple Basal Cell Carcinomas (PDT-Vismo)
|ClinicalTrials.gov Identifier: NCT02639117|
Recruitment Status : Completed
First Posted : December 24, 2015
Last Update Posted : July 18, 2018
This is a Phase 1 single site study to evaluate the safety and efficacy of a combination therapy that includes the administration of vismodegib and photodynamic therapy (PDT) using aminolevulinic acid (20 percent ALA) for multiple basal cell carcinomas. All subjects will receive vismodegib 150mg by mouth every day for 3 months, and undergo three PDT sessions with topical application of ALA. The PDT will be first administered at 7+ 4 business days after the beginning of the Erivedge and at 45 + 5 business days and then at 90 + 10 business days.
Primary Objective The primary objective of this study is to determine the safety of photodynamic therapy (PDT) with vismodegib (combination therapy) for patients with multiple BCC.
3.2 Secondary Objective To evaluate the overall response rate (ORR) to the combination therapy in patients with multiple BCCs.ORR is defined as the proportion of evaluable study subjects who has complete or partial response to the study treatment.
|Condition or disease||Intervention/treatment||Phase|
|Basal Cell Carcinoma||Drug: Vismodegib||Phase 1|
Use of PDT for the treatment of BCC Indications for PDT include superficial and nodular BCC. Eight randomized clinical trials have reported the results of PDT for superficial or nodular BCC with a total of 1583 patients. Results of the meta analysis showed overall complete clearance of PDT was 86.4 % compared to 98.2 % for surgery. The 1 year recurrence for PDT was 10.3 % vs 0. 6% for surgery. Cosmetic outcomes were much better with PDT than surgery. (Wang, 2015).
A randomized controlled trial of PDT with MAL versus surgical excision in 196 patients with superficial BCC showed a 9.3% recurrence rate for PDT versus a 0% recurrence rate for surgery at 12 months. However, the good-to-excellent cosmetic outcome was 94% and 60% for patients treated with PDT and surgical excision, respectively. Similarly, in trials of PDT versus surgery for nodular BCC, recurrence rates are less than 5% for surgery versus 14% to 30% for PDT with ALA. As with superficial BCC, cosmetic effects are consistently shown to be more favorable with PDT with ALA (Wang, 2015). In the largest single institution experience with 1440 nodular and superficial BCCs, PDT using systemically administered porfimer sodium showed an initial (6-month) complete response rate of 92%, with a recurrence rate of less than 10% at 4 years. At this same institution, a 92% complete response rate was achieved with PDT with topical ALA in 330 patients with superficial BCC, but the response rate dropped to 71% in 75 patients with nodular BCC.
In a multicenter randomized trial of PDT with MAL versus cryotherapy for superficial BCC, complete response rates at 3 months were 97% and 95%, respectively, with 5-year recurrence rates of 22% and 20% for PDT with MAL and cryotherapy, respectively. In this study, the excellent-to-good cosmetic outcome was 89% for PDT with MAL and 50% for cryotherapy.
Several clinical studies have reported an increase in the initial response rate with a lower recurrence rate after repeated PDT sessions. Initial responses usually are apparent between 3-6 months after treatment when the skin has healed over and treatment related changes have resolved. Cycles of MAL PDT repeated after 3 months for persistent BCC has been shown to offer high and durable response rates. Both efficacy and safety have also been demonstrated using repeated sessions with red or blue light at follow up times of 3, 6 and 12 months. At Roswell Park Cancer Institute, Oseroff and colleagues safely used repeated sessions of ALA PDT in children with BCNS (multiple BCC), and Gilchrest also reported the benefits of ALA PDT with red light at 2-4 month interval treatments.
The most common adverse event with either ALA or MAL PDT is the burning or stinging pain experienced by patients during illumination. Zeitouni and colleagues published their retrospective and prospective data using a 2 step irradiance approach with ALA/MAL PDT and red light in non BCNS patients with multiple BCC. Follow up times ranged from 6-24 months. The 2 step irradiance schedule (bilevel) effectively minimized the treatment related pain and maintained good clinical outcomes (Zeitouni x 2).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Photodynamic Therapy and Vismodegib for Multiple Basal Cell Carcinomas|
|Actual Study Start Date :||November 30, 2015|
|Actual Primary Completion Date :||November 2, 2016|
|Actual Study Completion Date :||November 18, 2017|
Vismodegib 150 mgs po qd. Open label.
Vismodegib 150 mgs po qd for 3 months
Other Name: Erivedge
- The number of participants with treatment related adverse events as assessed by the CTCAE v4.0 [ Time Frame: 2 years ]The proportion of evaluable study participants who had a grade 3 or higher adverse event (AE) or any serious adverse event that's determined to be at least possibly or probably related to study treatment, or any AE which is at least possibly or probably related to study treatment that causes permanent study discontinuation.
- The number of participants with overall response rate [ Time Frame: 2 years ]
To evaluate the overall response rate (ORR) to the combination therapy in patients with multiple BCCs. ORR is defined as the proportion of evaluable study subjects who has complete or partial response to the study treatment.
Complete response (CR): Disappearance of all target lesions Partial response (PR): At least a 30% decrease in the sum of the diameters of target lesion, taking as reference the baseline sum diameters.
- The number of participants wtih progressive disease or stable disease [ Time Frame: 2 years ]
The proportion of evaluable subjects with progressive disease (PD), and the proportion of evaluable subjects with stable disease (SD). Progressive Disease (PD): At least a 20% increase in the sum of the diameter of target lesions, taking as references the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. The appearance of one or more new lesions is also considered progression.
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD, taking as reference the smallest sum diameter while on study. Subjects having a documented response with no confirmation of the response will be listed with stable disease.
- The number of patients with complete histological clearance [ Time Frame: 2 years ]Complete histological clearance (CHC): Negative for BCC on punch biopsy at the end of the follow up visits.
- Overall treatment related pain during PDT assessed with the 11 point visual analogue scale (VAS) . [ Time Frame: 2 years ]Pain scores (VAS) of each patientwill be recorded at three time points (beginning, midway and end of PDT session). The mean score (±) SD of the study population will be calculated at each time point. Mean pain scores of study population will be compared with each other. In addition Mean Difference of pain scores before and after PDT of each patient will be calculated and an average (sum) of mean difference values of all patients will be measured
- Overall cosmetic scores on a scale of 1-5. [ Time Frame: 2 years ]Cosmesis will be evaluated by the investigator at the end of treatment and be rated as 1. Poor (hypertrophic scarring, significant hypo/hyper pigmentation), 2. Fair (flat scar,moderate pigmentation changes ) 3 .Good (mild pigmentation changes and scar changes) 4. Excellent (min to no pigmentation changes) 5. Still healing.The cosmetic scores will be recorded after all treatments, and tabulated for each lesion.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02639117
|United States, Arizona|
|Arizona Cancer Center|
|Tucson, Arizona, United States, 85719|
|Study Chair:||Mariette Marsh||University of Arizona Human Subjects Protection Program|