scholarly journals Randomized Phase II Trial of Bevacizumab or Temsirolimus in Combination With Chemotherapy for First Relapse Rhabdomyosarcoma: A Report From the Children’s Oncology Group

2019 ◽  
Vol 37 (31) ◽  
pp. 2866-2874 ◽  
Author(s):  
Leo Mascarenhas ◽  
Yueh-Yun Chi ◽  
Pooja Hingorani ◽  
James R. Anderson ◽  
Elizabeth R. Lyden ◽  
...  
Keyword(s):  
Phase Ii ◽  
Day Treatment ◽  
Objective Response ◽  
Local Tumor Control ◽  
Tumor Control ◽  
P Value ◽  
Additional Investigation ◽  
Randomized Phase Ii ◽  
First Relapse

PURPOSE The primary aim of this clinical trial was to prioritize bevacizumab or temsirolimus for additional investigation in rhabdomyosarcoma (RMS) when administered in combination with cytotoxic chemotherapy to patients with RMS in first relapse with unfavorable prognosis. PATIENTS AND METHODS Patients were randomly assigned to receive bevacizumab on day 1 or temsirolimus on days 1, 8, and 15 of each 21-day treatment cycle, together with vinorelbine on days 1 and 8, and cyclophosphamide on day 1 for a maximum of 12 cycles. Local tumor control with surgery and/or radiation therapy was permitted after 6 weeks of treatment. The primary end point was event-free survival (EFS). Radiographic response was assessed at 6 weeks. The study had a phase II selection that was design to detect a 15% difference between the two regimens (α = .2; 1-β = 0.8; two sided test). RESULTS Eighty-seven of 100 planned patients were enrolled when the trial was closed after the second interim analysis after 46 events occurred in 68 patients with sufficient follow-up. The O’Brien Fleming boundary at this analysis corresponded to a two-sided P value of .058 with an observed two-sided P value of .003 favoring temsirolimus. The 6-month EFS for the bevacizumab arm was 54.6% (95% CI, 39.8% to 69.3%) and 69.1% (95% CI, 55.1% to 83%) for the temsirolimus arm. Objective response rates were 28% (95% CI, 13.7% to 41.3%) and 47% (95% CI, 31.5% to 63.2%) for the bevacizumab and temsirolimus arms, respectively ( P = .12) and, 28% of patients on bevacizumab and 11% on temsirolimus had progressive disease at 6 weeks. CONCLUSION Patients who received temsirolimus had a superior EFS compared with bevacizumab. Temsirolimus has been selected for additional investigation in newly diagnosed patients with intermediate-risk RMS.

Randomized phase II study of 6 versus 12 months of adjuvant imatinib for patients with intermediate- or high-risk GIST.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 9-9
Author(s):  
Kazuya Muguruma ◽  
Yukinori Kurokawa ◽  
Toshimasa Tsujinaka ◽  
Junya Fujita ◽  
Takuya Nakai ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Interim Analysis ◽  
Phase Ii Study ◽  
Hazard Ratio ◽  
P Value ◽  
Adjuvant Imatinib ◽  
Randomized Phase Ii ◽  
Ecog Ps

9 Background: The Z9001 study revealed adjuvant imatinib for 1 year significantly improved RFS in GIST patients (pts). The SSGXVIII study compared 3 years with 1 year of adjuvant imatinib for high risk GIST pts, but there was no study to evaluate shorter period of imatinib administration than 1 year. We conducted a randomized phase II study to compare 6 months (6-mo) with 12 months (12-mo) adjuvant imatinib for intermediate or high risk GIST pts. Methods: Inclusion criteria included ECOG-PS of 0 or 1, age between 20 and 79 years, and primary KIT-positive GIST with intermediate or high risk according to the Fletcher criteria. Pts were randomized assigned to the 6-mo or 12-mo treatment of imatinib 400 mg/day after complete resection. The primary endpoint was recurrence-free survival (RFS). The study was designed as a randomized screening trial to evaluate non-inferiority with margin of hazard ratio 1.67, 1-sided alpha 0.2 and power 0.8. Results: Ninety-two pts were randomly allocated the 6-mo group (n=45) or the 12-mo group (n=47) between Dec 2007 and Aug 2011, which was well balanced for baseline characteristics. One patient was ineligible due to non-GIST (desmoid) tumor at a central review. The proportions of pts completed their assigned adjuvant treatment were 80% in the 6-mo and 70% in the 12-mo group. The first interim analysis was conducted at Sep 2012 with the median follow-up time of 33 months. The 1- and 2-year RFS were 82% and 65% in the 6-mo group and 96% and 86% in the 12-mo group, respectively. Hazard ratio of recurrence was 1.81 (95%CI: 0.84-3.91), and the 2-sided log-rank p value was 0.12. Adjuvant imatinib was well tolerated, with one patient of Gr. 4 rash and no treatment-related death. Because of the lower efficacy of the 6-mo group than expected, the Data and Safety Monitoring Committee recommended the early release of first interim analysis results. Conclusions: Adjuvant Imatinib for 6-mo was inferior in efficacy to that for 12-mo in terms of RFS. Shortening of the adjuvant imatinib duration is not recommended for intermediate or high risk GIST pts. Clinical trial information: UMIN000000950.

scholarly journals International Rare Cancers Initiative Multicenter Randomized Phase II Trial of Cisplatin and Fluorouracil Versus Carboplatin and Paclitaxel in Advanced Anal Cancer: InterAAct

2020 ◽  
Vol 38 (22) ◽  
pp. 2510-2518 ◽  
Author(s):  
Sheela Rao ◽  
Francesco Sclafani ◽  
Cathy Eng ◽  
Richard A. Adams ◽  
Marianne G. Guren ◽  
...  
Keyword(s):  
Phase Ii ◽  
Anal Cancer ◽  
Objective Response ◽  
Area Under The Curve ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Serious Adverse Events ◽  
Randomized Phase Ii ◽  
Reduced Toxicity

PURPOSE To compare cisplatin plus fluorouracil (FU) versus carboplatin plus paclitaxel in chemotherapy-naïve advanced anal cancer to establish the optimal regimen. PATIENTS AND METHODS Patients who had not received systemic therapy for advanced anal cancer were randomly assigned 1:1 to intravenous cisplatin 60 mg/m2 (day 1) plus FU 1,000 mg/m2 (days 1-4) every 21 days or carboplatin (area under the curve, 5; day 1) plus paclitaxel 80 mg/m2 (days 1, 8, and 15) every 28 days for 24 weeks, until disease progression, intolerable toxicity, or withdrawal of consent. Primary end point was objective response rate (ORR). Primary and secondary end points were assessed in a hierarchic model to compare the regimens and pick the winner. RESULTS We conducted an international multicenter randomized phase II study in 60 centers between December 2013 and November 2017. Median follow-up was 28.6 months. A total of 91 patients were randomly assigned: 46 to cisplatin plus FU and 45 to carboplatin plus paclitaxel. ORR was 57% (95% CI, 39.4% to 73.7%) for cisplatin plus FU versus 59% (95% CI, 42.1% to 74.4%) for carboplatin plus paclitaxel. More serious adverse events were noted in the cisplatin plus FU arm (62%) compared with the carboplatin plus paclitaxel arm (36%; P = .016). Median progression-free survival was 5.7 months (95% CI, 3.3 to 9.0 months) for cisplatin plus FU compared with 8.1 months (95% CI, 6.6 to 8.8 months) for carboplatin plus paclitaxel. Median overall survival was 12.3 months for cisplatin plus FU (95% CI, 9.2 to 17.7 months) compared with 20 months (95% CI, 12.7 months to not reached) for carboplatin plus paclitaxel (hazard ratio, 2.00; 95% CI, 1.15 to 3.47; P = .014). CONCLUSION This is the first international randomized trial to our knowledge conducted in chemotherapy-naïve advanced anal cancer. Although there was no difference in ORR, the association with clinically relevant reduced toxicity and a trend toward longer survival suggest that carboplatin plus paclitaxel should be considered as a new standard of care.

Gamma Knife surgery combined with resection for treatment of a single brain metastasis: preliminary results

2010 ◽  
Vol 113 (Special_Supplement) ◽  
pp. 90-96 ◽  
Author(s):  
M. Yashar S. Kalani ◽  
Aristotelis S. Filippidis ◽  
Maziyar A. Kalani ◽  
Nader Sanai ◽  
David Brachman ◽  
...  
Keyword(s):  
Survival Data ◽  
Initial Treatment ◽  
Median Survival Time ◽  
Local Tumor Control ◽  
Survival Duration ◽  
Tumor Control ◽  
Local Tumor ◽  
Systemic Control ◽  
Cranial Metastasis

Object Resection and whole-brain radiation therapy (WBRT) have classically been the standard treatment for a single metastasis to the brain. The objective of this study was to evaluate the use of Gamma Knife surgery (GKS) as an alternative to WBRT in patients who had undergone resection and to evaluate patient survival and local tumor control. Methods The authors retrospectively reviewed the charts of 150 patients treated with a combination of stereotactic radiosurgery and resection of a cranial metastasis at their institution between April 1997 and September 2009. Patients who had multiple lesions or underwent both WBRT and GKS were excluded, as were patients for whom survival data beyond the initial treatment were not available. Clinical and imaging follow-up was assessed using notes from clinic visits and MR imaging studies when available. Follow-up data beyond the initial treatment and survival data were available for 68 patients. Results The study included 37 women (54.4%) and 31 men (45.6%) (mean age 60 years, range 28–89 years). In 45 patients (66.2%) there was systemic control of the primary tumor when the cranial metastasis was identified. The median duration between resection and radiosurgery was 15.5 days. The median volume of the treated cavity was 10.35 cm3 (range 0.9–45.4 cm3), and the median dose to the cavity margin was 15 Gy (range 14–30 Gy), delivered to the 50% isodose line (range 50%–76% isodose line). The patients' median preradiosurgery Karnofsky Performance Scale (KPS) score was 90 (range 40–100). During the follow-up period we identified 27 patients (39.7%) with recurrent tumor located either local or distant to the site of treatment. The median time from primary treatment of metastasis to recurrence was 10.6 months. The patients' median length of survival (interval between first treatment of cerebral metastasis and last follow-up) was 13.2 months. For the patient who died during follow-up, the median time from diagnosis of cerebral metastasis to death was 11.5 months. The median duration of survival from diagnosis of the primary cancer to last follow-up was 30.2 months. Patients with a pretreatment KPS score ≥ 90 had a median survival time of 23.2 months, and patients with a pretreatment KPS score < 90 had a median survival time of 10 months (p < 0.008). Systemic control of disease at the time of metastasis was not predictive of increased survival duration, although it did tend to improve survival. Conclusions Although the debate about the ideal form of radiation treatment after resection continues, these findings indicate that GKS combined with surgery offers comparable survival duration and local tumor control to WBRT for patients with a diagnosis of a single metastasis.

scholarly journals Stereotactic radiosurgery for treating meningiomas eligible for complete resection

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Maximilian I. Ruge ◽  
Juman Tutunji ◽  
Daniel Rueß ◽  
Eren Celik ◽  
Christian Baues ◽  
...  
Keyword(s):  
Adverse Events ◽  
Stereotactic Radiosurgery ◽  
Medical Condition ◽  
Local Tumor Control ◽  
Complete Resection ◽  
Neurological Deficits ◽  
Tumor Control ◽  
Recurrence Rates ◽  
Treatment Volume

Abstract Background For meningiomas, complete resection is recommended as first-line treatment while stereotactic radiosurgery (SRS) is established for meningiomas of smaller size considered inoperable. If the patient´s medical condition or preference excludes surgery, SRS remains a treatment option. We evaluated the efficacy and safety of SRS in a cohort comprising these cases. Methods In this retrospective single-centre analysis we included patients receiving single fraction SRS either by modified LINAC or robotic guidance by Cyberknife for potentially resectable intracranial meningiomas. Treatment-related adverse events as well as local and regional control rates were determined from follow-up imaging and estimated by the Kaplan–Meier method. Results We analyzed 188 patients with 218 meningiomas. The median radiological, and clinical follow-up periods were 51.4 (6.2–289.6) and 55.8 (6.2–300.9) months. The median tumor volume was 4.2 ml (0.1–22), and the mean marginal radiation dose was 13.0 ± 3.1 Gy, with reference to the 80.0 ± 11.2% isodose level. Local recurrence was observed in one case (0.5%) after 239 months. The estimated 2-, 5-, 10- and 15-year regional recurrence rates were 1.5%, 3.0%, 6.6% and 6.6%, respectively. Early adverse events (≤ 6 months after SRS) occurred in 11.2% (CTCEA grade 1–2) and resolved during follow-up in 7.4% of patients, while late adverse events were documented in 14.4% (grade 1–2; one case grade 3). Adverse effects (early and late) were associated with the presence of symptoms or neurological deficits prior to SRS (p < 0.03) and correlated with the treatment volume (p < 0.02). Conclusion In this analysis SRS appears to be an effective treatment for patients with meningiomas eligible for complete resection and provides reliable long-term local tumor control with low rates of mild morbidity.

scholarly journals Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis

2021 ◽  
Author(s):  
Irene Bargellini ◽  
Valentina Lorenzoni ◽  
Giulia Lorenzoni ◽  
Paola Scalise ◽  
Gianni Andreozzi ◽  
...  
Keyword(s):  
Propensity Score ◽  
Tumor Progression ◽  
Tumor Response ◽  
Complete Response ◽  
Tumor Burden ◽  
Local Tumor Control ◽  
Lower Number ◽  
Tumor Control ◽  
Duration Of Response

Abstract Objectives To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). Methods We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. Results Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). Conclusion Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. Key Points • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

Radiosurgery for Treatment of Recurrent Intracranial Hemangiopericytomas

Neurosurgery ◽  
2002 ◽  
Vol 51 (4) ◽  
pp. 905-911 ◽  
Author(s):  
Jason Sheehan ◽  
Douglas Kondziolka ◽  
John Flickinger ◽  
L. Dade Lunsford
Keyword(s):  
Stereotactic Radiosurgery ◽  
Survival Rates ◽  
Gamma Knife Radiosurgery ◽  
Residual Tumor ◽  
Local Tumor Control ◽  
Tumor Control ◽  
Local Tumor ◽  
University Of Pittsburgh ◽  
Kaplan Meier

Abstract OBJECTIVE Hemangiopericytomas are highly aggressive meningeal tumors with tendencies for recurrence and metastasis. The purpose of this retrospective, single-institution review was to evaluate the efficacy and role of stereotactic radiosurgery in the management of recurrent hemangiopericytomas. METHODS We reviewed data for patients who underwent stereotactic radiosurgery at the University of Pittsburgh between 1987 and 2001. Fourteen patients underwent radiosurgery for 15 discrete tumors. Prior treatments included transsphenoidal resection (n = 1), craniotomy and resection (n = 27), embolization (n = 1), and conventional radiotherapy (n = 7). Clinical and radiological responses were evaluated. Follow-up periods varied from 5 to 76 months (mean, 31.3 mo; median, 21 mo). The mean radiation dose to the tumor margin was 15 Gy. RESULTS Seventy-nine percent of patients (11 of 14 patients) with recurrent hemangiopericytomas demonstrated local tumor control after radiosurgery. Twelve of 15 tumors (i.e., 80%) dramatically decreased in size on follow-up imaging scans. Regional intracranial recurrences were retreated with radiosurgery for two patients (i.e., 15%); neither of those two patients experienced long-term tumor control. Local recurrences occurred 12 to 75 months (median, 21 mo) after radiosurgery. Local tumor control and survival rates at 5 years after radiosurgery were 76 and 100%, respectively (Kaplan-Meier method). We could not correlate prior irradiation or tumor size with tumor control. Twenty-nine percent of the patients (4 of 14 patients) developed remote metastases. Radiosurgery did not seem to offer protection against the development of intra- or extracranial metastases. CONCLUSION Gamma knife radiosurgery provided local tumor control for 80% of recurrent hemangiopericytomas. When residual tumor is identified after resection or radiotherapy, early radiosurgery should be considered as a feasible treatment modality. Despite local tumor control, patients are still at risk for distant metastasis. Diligent clinical and radiological follow-up monitoring is necessary.

Linear Accelerator Radiosurgery for Nonvestibular Schwannomas

Neurosurgery ◽  
2011 ◽  
Vol 68 (4) ◽  
pp. 974-984 ◽  
Author(s):  
Matthew M. Kimball ◽  
Kelly D. Foote ◽  
Frank J. Bova ◽  
Yueh-Yun Chi ◽  
William A. Friedman
Keyword(s):  
Surgical Resection ◽  
Cranial Nerve ◽  
Linear Accelerator ◽  
Jugular Foramen ◽  
Symptomatic Improvement ◽  
Local Tumor Control ◽  
Tumor Control ◽  
High Morbidity ◽  
Local Tumor

Abstract BACKGROUND: Nonvestibular schwannomas are uncommon tumors of the brain often treated by surgical resection. Surgery may be associated with high morbidity. OBJECTIVE: We present a series of nonvestibular schwannomas treated with linear accelerator radiosurgery during a 19-year period. METHODS: This is a retrospective analysis of patients who underwent treatment of nonvestibular schwannomas at the University of Florida with linear accelerator radiosurgery between August 1989 and February 2008. Forty-nine patients underwent treatment during the study period, and 6 were lost to follow up. The mean age was 51 years (range, 17-82 years), 39% had previous surgical resection, and 67% presented with preradiosurgery cranial nerve deficits. There were 25 trigeminal, 18 jugular foramen, 2 facial, 2 oculomotor, 1 hypoglossal, and 1 high cervical schwannomas. The median tumor volume was 5.3 mL (range, 0.3-24.5 mL), treated with a median dose of 1250 cGy (range, 1000-1500 cGy). Study endpoints were actuarial local tumor control and neurological outcome. RESULTS: Forty-three patients were available for a median follow-up of 37 months (range, 6-210 months). Actuarial local tumor control was 97% at 1 year, 91% at 4.5 years, and 83% at 5 years. There were 4 new cranial nerve deficits (9%) including facial numbness (2 patients), anesthesia dolorosa (1 patient), and facial weakness (1 patient). Thirty-nine percent had documented clinical and/or symptomatic improvement. There were no other morbidity and no mortality with treatment. CONCLUSION: Radiosurgery for nonvestibular schwannomas offers good actuarial local tumor control and has superior morbidity compared with surgical resection. This is the largest linear accelerator radiosurgical series, and the second largest radiosurgical series reported to date.

Updated report of a phase II randomized trial of transoral surgical resection followed by low-dose or standard postoperative therapy in resectable p16+ locally advanced oropharynx cancer: A trial of the ECOG-ACRIN cancer research group (E3311).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6010-6010
Author(s):  
Robert L. Ferris ◽  
Yael Flamand ◽  
Gregory S. Weinstein ◽  
Shuli Li ◽  
Harry Quon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Standard Dose ◽  
Locally Advanced ◽  
Oncologic Outcome ◽  
Smoking History ◽  
Transoral Surgery ◽  
P Value ◽  
Oropharynx Cancer ◽  
Patient Reported

6010 Background: Definitive or postoperative chemoradiation (CRT) is highly curative for human papillomavirus-associated (HPV+) oropharynx cancer (OPC) but induces significant toxicity. As a potential deintensification strategy, we studied primary transoral surgery (TOS) and, in intermediate pathologic risk patients, reduced dose postoperative RT (PORT). Methods: E3311 is a phase II trial with randomization to reduced- or standard-dose PORT for resected stage III-IVa (AJCC7) intermediate pathologic risk HPV+ OPC, stratified by smoking history. Primary endpoints have been reported; we now present updated 3-year PFS and patient-reported outcomes (PRO), including head and neck-cancer specific quality of life (FACT-H&N) and swallowing perception and performance (MDADI). Results: Of 519 enrolled patients, 495 underwent TOS. The primary oncologic endpoint was 2-year PFS for 50 Gy (Arm B) or 60Gy (Arm C). Among 360 eligible and treated patients (ETP), Arm A (observation, N = 38) enrolled 11%, Arms B (N = 100) or C (N = 109) randomized 58%, and Arm D (66Gy + weekly cisplatin, N = 113) enrolled 31%. With 35.1 months median follow-up, 3-year PFS Kaplan-Meier estimate is 96.9% (90% CI [91.9%, 100%]) for Arm A; 94.9% (90% CI [91.3%, 98.6%]) for Arm B; 93.5% (90% CI [89.4%, 97.9%]) for Arm C; and 90.7% (90% CI [86.2%, 95.4%]) for Arm D. Recurrences and death without recurrence were 4 and 1 in Arm B, and 5 and one in Arm C. Smokers ( > 10 pack-years) did not have worse 3-year PFS in Arms B or C. Treatment arm distribution and outcome for ineligible patients who started adjuvant therapy mirrored the 360 ETP. A comparison combining arms B/C versus arm D in the proportion of patients stable/improved in FACT-H&N total score, from baseline to 6 months post-treatment as a pre-specified endpoint, was 56% vs. 38% (p value = 0.011, one-sided Fisher’s exact test); however, underlying differences in treatment and risk may be confounding. An exploratory comparison between Arms B and C revealed improvement in FACT H&N (63% in Arm B vs. 49% in Arm C had a stable/improved score, p-value = 0.056). Conclusions: Primary TOS and reduced PORT retained outstanding oncologic outcome at 35 months follow up, with favorable QOL and functional outcomes, in intermediate risk HPV+ OPC. Clinical trial information: NCT 01898494.

PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS143-TPS143
Author(s):  
John H. Strickler ◽  
Fang-Shu Ou ◽  
Tanios S. Bekaii-Saab ◽  
Christine Megerdichian Parseghian ◽  
Andrea Cercek ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Benefit ◽  
Objective Response ◽  
Progression Free Survival ◽  
Wild Type ◽  
Open Label ◽  
Genomic Alterations ◽  
Open Label Study ◽  
Label Study ◽  
Randomized Phase Ii

TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency > 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456.

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