A Phase II Study of Pembrolizumab, Carboplatin, Paclitaxel, and Radiation for the Treatment of Early-Stage Anal Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Anal Cancer
- Sponsor
- Dustin Deming
- Enrollment
- 23
- Locations
- 7
- Primary Endpoint
- Clinical complete response rate (cCR) following weekly carboplatin and paclitaxel in combination with pembrolizumab and radiation for the treatment of early-stage anal cancer.
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
A single arm phase II study of pembrolizumab, carboplatin, paclitaxel, and radiation for the treatment of early-stage anal cancer. There are 2 treatments phases and then surveillance. The first treatment phase is the chemoradiation phase (Cycle 1-6, weekly cycles) which is followed by the maintenance phase (Cycle 7-14, 6 week cycles).
Investigators
Dustin Deming
Sponsor-Investigator
Hoosier Cancer Research Network
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age ≥ 18 years at the time of consent.
- •ECOG Performance Status of 0-1 within 30 days prior to registration.
- •Histologically proven stage I (T1N0), IIA (T2N0), IIB (T1/2N1), or IIIA (T3 N0/1) invasive squamous cell carcinoma of the anus by AJCC version
- •Stage IIIB/C (T4 N0/1) cancers will also be eligible if less than 5cm in diameter.
- •Patient deemed ineligible for standard of care treatment with 5-fluorouracil (5FU) and mitomycin-C (MMC) concurrently with radiation per treating investigator.
- •Patient is treatment naïve for anal cancer diagnosis.
- •Evaluable disease according to RECIST v1.1 within 30 days prior to registration.
- •Archival or newly obtained tissue available for planned correlative analysis. If tissue is not available, subjects may choose to have a standard of care biopsy to meet eligibility.
- •Demonstrate adequate organ function as defined below. All screening labs to be obtained within 30 days prior to registration.
Exclusion Criteria
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- •Has known additional malignancy that is progressing or has required active treatment within the past 2 years and is not deemed by the investigator to be at low risk for recurrence.
- •Notes: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (ex. cervical, breast) that have undergone potentially curative therapy are eligible. Participants with carcinoma in situ of the bladder are not eligible. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤8, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are eligible.
- •Pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug(s). NOTE: breast milk cannot be stored for future use while the mother is being treated on study.
- •Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- •Patients with an active autoimmune disease requiring immunosuppression in the past 2 years.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy equivalent to \> 10mg prednisone per day or any other form of immunosuppressive therapy within 7 days prior to registration. NOTE: Topical corticosteroid or inhaled corticosteroids are allowed.
- •Has received a live vaccine or live-attenuated vaccine within 30 days prior to registration. Administration of killed vaccines is allowed. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, BCG, and typhoid oral vaccine. Intranasal influenza vaccines (e.g., Flu-Mist ®) are live attenuated vaccines and are not allowed. NOTE: No live vaccines may be administered while participating in the trial.
- •Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- •Has received any investigational drug or used an investigational device for the treatment of anal cancer within 30 days prior to registration.
Arms & Interventions
Pembrolizumab plus carbopltin and paclitaxel
All patients in the chemoradiation phase will receive a combination of pembrolizumab, carboplatin, and paclitaxel. For the first 6 cycles (a cycle is a week) carboplatin and paclitaxel will be administered by IV every week. Pembrolizumab will be administered by IV on cycles 1 and 4. The next phase is the maintenance phase. This will occur from cycle 7-14 with each cycle being 6 weeks. Pembrolizumab will be administered every cycle.
Intervention: Pembrolizumab
Pembrolizumab plus carbopltin and paclitaxel
All patients in the chemoradiation phase will receive a combination of pembrolizumab, carboplatin, and paclitaxel. For the first 6 cycles (a cycle is a week) carboplatin and paclitaxel will be administered by IV every week. Pembrolizumab will be administered by IV on cycles 1 and 4. The next phase is the maintenance phase. This will occur from cycle 7-14 with each cycle being 6 weeks. Pembrolizumab will be administered every cycle.
Intervention: Paclitaxel
Pembrolizumab plus carbopltin and paclitaxel
All patients in the chemoradiation phase will receive a combination of pembrolizumab, carboplatin, and paclitaxel. For the first 6 cycles (a cycle is a week) carboplatin and paclitaxel will be administered by IV every week. Pembrolizumab will be administered by IV on cycles 1 and 4. The next phase is the maintenance phase. This will occur from cycle 7-14 with each cycle being 6 weeks. Pembrolizumab will be administered every cycle.
Intervention: Carboplatin
Pembrolizumab plus carbopltin and paclitaxel
All patients in the chemoradiation phase will receive a combination of pembrolizumab, carboplatin, and paclitaxel. For the first 6 cycles (a cycle is a week) carboplatin and paclitaxel will be administered by IV every week. Pembrolizumab will be administered by IV on cycles 1 and 4. The next phase is the maintenance phase. This will occur from cycle 7-14 with each cycle being 6 weeks. Pembrolizumab will be administered every cycle.
Intervention: Radiation
Outcomes
Primary Outcomes
Clinical complete response rate (cCR) following weekly carboplatin and paclitaxel in combination with pembrolizumab and radiation for the treatment of early-stage anal cancer.
Time Frame: 6 months
Meets both of the following criteria: 1. There is no documented residual cancer on anoscopy. If residual cancer is suspected, a biopsy must be obtained. 2. No documented residual cancer or new metastatic disease on PET/CT, or if a PET/CT cannot be obtained, CT or MR imaging with contrast can be used. Physiologic PET avidity in the anal canal without evidence of cancer on anoscopy is still consistent with a clinical complete response.
Secondary Outcomes
- Percentage of subjects with treatment emergent grade 3-4 toxicities, as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.(3 years)
- Assess tumor downstaging(3 years)
- Assess the overall response rate of weekly carboplatin and paclitaxel in combination with pembrolizumab and radiation for the treatment of anal cancer.(3 years)
- Disease-free survival of patients undergoing this treatment strategy.(3 years)